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Horine SV, Rakesh N, Nadav D, Gulati A. Perioperative Pain Management in Patients With Cancer-Related Pain: A Narrative Review. Anesth Analg 2025; 140:833-845. [PMID: 39883582 DOI: 10.1213/ane.0000000000007399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2025]
Abstract
The number of cancer patients, cancer survivors, and cancer surgeries is expected to continue to grow and anesthesiologists will benefit from having a framework on how to approach treating perioperative pain in the oncologic population. This article presents general considerations for formulating a perioperative pain management plan including cancer-specific contraindications for epidurals and nerve blocks, common procedures for pain after thoracic and abdominal surgeries, and alternative pain management techniques.
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Affiliation(s)
- Storm V Horine
- From the Department of Anesthesiology & Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
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Ben Khaled N, Möller M, Jochheim LS, Leyh C, Ehmer U, Böttcher K, Pinter M, Balcar L, Scheiner B, Weich A, Leicht HB, Zarka V, Ye L, Schneider J, Piseddu I, Öcal O, Rau M, Sinner F, Venerito M, Gairing SJ, Förster F, Mayerle J, De Toni EN, Geier A, Reiter FP. Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multicenter real-world study with focus on bleeding and thromboembolic events. JHEP Rep 2024; 6:101065. [PMID: 38798717 PMCID: PMC11126929 DOI: 10.1016/j.jhepr.2024.101065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/24/2024] [Accepted: 03/07/2024] [Indexed: 05/29/2024] Open
Abstract
Background & Aims Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs. lenvatinib in a large, multicenter real-world population. Methods This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared. Results In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib (p = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib (p = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort (p = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months. Conclusions Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib. Impact and implications The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib.
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Affiliation(s)
- Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Marie Möller
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Leonie S. Jochheim
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Catherine Leyh
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Ursula Ehmer
- Department of Internal Medicine II, University Hospital Rechts der Isar, TUM School of Medicine and Health, Department Clinical Medicine, Munich, Germany
| | - Katrin Böttcher
- Department of Internal Medicine II, University Hospital Rechts der Isar, TUM School of Medicine and Health, Department Clinical Medicine, Munich, Germany
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Alexander Weich
- Division of Gastroenterology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Hans Benno Leicht
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Valentina Zarka
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Liangtao Ye
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Julia Schneider
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Ignazio Piseddu
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Osman Öcal
- Department Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Monika Rau
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Friedrich Sinner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany
| | - Simon Johannes Gairing
- Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany
| | - Friedrich Förster
- Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany
| | - Julia Mayerle
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Enrico N. De Toni
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Andreas Geier
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Florian P. Reiter
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
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De Gaetano V, Pallozzi M, Cerrito L, Santopaolo F, Stella L, Gasbarrini A, Ponziani FR. Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives. Cancers (Basel) 2024; 16:1388. [PMID: 38611066 PMCID: PMC11011056 DOI: 10.3390/cancers16071388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors". Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.
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Affiliation(s)
- Valeria De Gaetano
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Maria Pallozzi
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Lucia Cerrito
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Francesco Santopaolo
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Leonardo Stella
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
| | - Antonio Gasbarrini
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, Centro Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario GemelliIstituto di Ricovero e Cura a Carattere Scientifico, IRCCS, 00168 Rome, Italy; (V.D.G.); (M.P.); (L.C.); (F.S.); (L.S.); (F.R.P.)
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Ge P, Han C, Reyila A, Liu D, Hong W, Liu J, Zhang J, Han X, Li X, Huang M, Fan S, Kaierdebieke A, Wu X, Huang X, Guo W, Liu S, Bian Y. Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis. Medicine (Baltimore) 2023; 102:e34793. [PMID: 37657052 PMCID: PMC10476758 DOI: 10.1097/md.0000000000034793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 07/26/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.
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Affiliation(s)
- Pu Ge
- Institute of Chinese Medical Sciences, University of Macau, Macau, China
- State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macau, China
| | - Chunyan Han
- School of Political Science and Public Administration, Shandong University, Qingdao, China
| | | | - Diyue Liu
- International School of Public Health and One Health, Hainan Medical University, Haikou, China
| | - Wenying Hong
- Faculty of Health Sciences, University of Macau, Macau, China
| | - Jiaxin Liu
- Xiangya School of Nursing, Central South University, Changsha, China
| | - Jinzi Zhang
- School of Humanities and Social Sciences, Harbin Medical University, Harbin, China
| | - Xiao Han
- The Fifth Affiliated Hospital of Sun Yat-sat University, Zhuhai, China
| | - Xialei Li
- School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Mengjie Huang
- School of Public Health, Shandong University, Jinan, China
| | - Siyuan Fan
- Department of Preventive Medicine, Yanjing Medical College, Capital Medical University, Beijing, China
| | | | - Xiaoyu Wu
- School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Xiaolu Huang
- Clinically Third Series, China Medical University, Shenyang, China
| | - Weirui Guo
- School of Clinical Medicine of Jining Medicine University, Jining, China
| | - Siyu Liu
- Stomatology College of Shandong University, Jinan, China
| | - Ying Bian
- Institute of Chinese Medical Sciences, University of Macau, Macau, China
- State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macau, China
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Chen Y, Du Y, Qiu L, Zheng J. Central retinal vein occlusion with cerebral infarction secondary to anlotinib treatment: a case report and literature review. Front Pharmacol 2023; 14:1188218. [PMID: 37383723 PMCID: PMC10293757 DOI: 10.3389/fphar.2023.1188218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/30/2023] [Indexed: 06/30/2023] Open
Abstract
Purpose: We present a rare case of an elderly man with minimal pre-existing thromboses risk, who experienced central retinal vein occlusion (CRVO) and cerebral infarction after oral intake of the anti-cancer drug anlotinib, likely due to a drug-related complication. Observations: A male, aged 65 years, sought care at the ophthalmology department because of acute painless 5-day vision loss in the right eye, in combination with cerebral infarction history, after oral intake of anlotinib for hepatocellular carcinoma (HCC) for over 16 months. Clinical assessment and ancillary examination verified a right eye central retinal vein occlusion diagnosis. Anlotinib is a multi-target tyrosine kinase inhibitors (TKIs) is reported to potently suppress vascular endothelial growth factor (VEGF) receptor, in order to exert strong antitumor angiogenesis and inhibit tumor occurrence. Although anlotinib is only regarded as a possible thrombosis risk factor, it is possible that anlotinib administration markedly enhanced vaso-occlusive risk within this patient. Conclusion and significance: Herein, we present the first report of anlotinib-induced CRVO and cerebral infarction to our knowledge. Given our evidences, anlotinib usage is intricately linked to sight- and life-threatening thrombotic effects even among patients with reduced thrombophilic risk. Hence, patients receiving this drug must be carefully monitored for possible drug-related complications.
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Affiliation(s)
- Yingying Chen
- Department of Ophthalmology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yi Du
- Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lu Qiu
- The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jing Zheng
- The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
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Lei H, Tao D, Zhang N, Sun M, Sun L, Yang D, Jiang Y, Zhou W, Xie Y, Wang Y. Nomogram prediction for the risk of venous thromboembolism in patients with lung cancer. Cancer Cell Int 2023; 23:40. [PMID: 36872336 PMCID: PMC9985855 DOI: 10.1186/s12935-023-02882-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/28/2023] [Indexed: 03/07/2023] Open
Abstract
OBJECTIVE The aim of this study was to establish a nomogram graph model to accurately predict the venous thromboembolism (VTE) risk probability in the general population with lung cancer. METHODS Based on data from patients with lung cancer in Chongqing University Cancer Hospital of China, the independent risk factors of VTE were identified by the logistic univariable and multivariable analysis and were integrated to construct a nomogram, which was validated internally. The predictive effectiveness of the nomogram was evaluated by the receiver operating characteristic curve (ROC) and calibration curve. RESULTS A total of 3398 lung cancer patients were included for analysis. The nomogram incorporated eleven independent VTE risk factors including karnofsky performance scale (KPS), stage of cancer, varicosity, chronic obstructive pulmonary disease (COPD), central venous catheter (CVC), albumin, prothrombin time (PT), leukocyte counts, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), dexamethasone, and bevacizumab. The C-index of the nomogram model was 0.843 and 0.791 in the training and validation cohort, respectively, demonstrating good discriminative power. The calibration plots of the nomogram revealed excellent agreement between the predicted and actual probabilities. CONCLUSIONS We established and validated a novel nomogram for predicting the risk of VTE in patients with lung cancer. The nomogram model could precisely estimate the VTE risk of individual lung cancer patients and identify high-risk patients who are in need of a specific anticoagulation treatment strategy.
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Affiliation(s)
- Haike Lei
- Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Dan Tao
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Ningning Zhang
- Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Mao Sun
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Lisi Sun
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Dingyi Yang
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Yong Jiang
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Wei Zhou
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China
| | - Yue Xie
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China.
| | - Ying Wang
- Department of Radiation Oncology, Chongqing University Cancer Hospital, 181, Hanyu Road, Shapingba District, Chongqing, 400030, China.
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
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Rho S, Wang C, Hosseini Dehkordi SH, Sears JJ, Hu ZI. Bleeding and thrombotic events in bevacizumab-treated patients with colorectal cancer on novel oral anticoagulants and antiplatelet medications. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2023; 27:100283. [PMID: 38511095 PMCID: PMC10945962 DOI: 10.1016/j.ahjo.2023.100283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/17/2023] [Accepted: 02/19/2023] [Indexed: 03/22/2024]
Abstract
Background Bevacizumab is a humanized monoclonal anti-VEGF antibody often given in combination with fluorouracil-based chemotherapy as therapy for metastatic colorectal cancer (mCRC). The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants with and without aspirin and bevacizumab treatment in patients with mCRC remain unclear. Methods 462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results 21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within three years of starting apixaban or rivaroxaban. Of the 13 patients without aspirin prescription, nine were given apixaban, and four were given rivaroxaban while on bevacizumab. Four out of nine of the patients who received apixaban had epistaxis, and only one case resulted in any treatment discontinuation. Three out of four of the patients who received rivaroxaban experienced bleeding, and one of these three patients discontinued bevacizumab. We also looked at eight patients who had received aspirin. Two out of seven patients who received apixaban/bevacizumab/aspirin experienced bleeding and discontinued a medication. The patient who received rivaroxaban/bevacizumab/aspirin experienced bleeding and discontinued bevacizumab. No patient experienced adverse thrombotic events. Conclusions Patients with mCRC treated with bevacizumab and apixaban with no history of aspirin use within three years have a relatively low risk of bleeding that warrants treatment discontinuation.
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Affiliation(s)
- Shinji Rho
- School of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Chris Wang
- School of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | | | - James J. Sears
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Z. Ian Hu
- Department of Medicine, Division of Oncology, Section of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA
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A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology. Int J Mol Sci 2023; 24:ijms24043169. [PMID: 36834580 PMCID: PMC9964264 DOI: 10.3390/ijms24043169] [Citation(s) in RCA: 108] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/29/2023] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1-2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.
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Zeng H, Xu Q, Wang J, Xu X, Luo J, Zhang L, Luo C, Ying J, Li J. The effect of anti-PD-1/PD-L1 antibodies combined with VEGF receptor tyrosine kinase inhibitors versus bevacizumab in unresectable hepatocellular carcinoma. Front Immunol 2023; 14:1073133. [PMID: 36756114 PMCID: PMC9900113 DOI: 10.3389/fimmu.2023.1073133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/02/2023] [Indexed: 01/24/2023] Open
Abstract
Introduction Immune checkpoint inhibition (ICI) plus bevacizumab (BEV) is the standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of ICI plus bevacizumab and ICI plus receptor tyrosine kinase inhibitor (TKI) in this patient population. Methods This retrospective single-institution study enrolled 94 patients with uHCC who received ICI plus TKI or bevacizumab as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were used to evaluate treatment efficacy. RECIST v1.1 criteria were used to calculate the objective clinical response. Common Terminology Criteria for Adverse Events were used to report and categorize adverse events. Results By the last follow-up interview on May 15, 2022, there were 57 deaths, and 19 patients did not develop disease progression. Thirty patients received sintilimab/atezolizumab plus bevacizumab (ICI + BEV group), and 64 received ICI plus TKI (ICI + TKI group). The median OS was 430 days (95% CI, 266-NA) in the ICI+TKI group and 498 days (95% CI, 349-NA) in the ICI+BEV group (HR, 1.20; 95% CI, 0.69-2.07; P = 0.52). There was no significant difference between the two groups in the median PFS (182 vs. 221 days, P=0.67). In the ICI+TKI group, the ORR and DCR were 28.1% and 67.2%, respectively. In the ICI+BEV group, the ORR and DCR were 26.7% and 66.7%, respectively. The overall incidence of adverse events was similar between the two groups. Palmar-plantar erythrodysesthesia syndrome (23[36%]) occurred only in the ICI + TKI group. Patients who received ICI+BEV were more prone to upper gastrointestinal bleeding (2 [7%]), with one patient with grade 4 requiring emergency DSA treatment. Conclusion This study found that ICI+TKI and ICI+BEV as first-line treatments were similar in OS, PFS, and tumor response in uHCC. Different populations are suitable for different regimens because of the different adverse events.
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Affiliation(s)
- Hui Zeng
- Department of Interventional Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Qi Xu
- Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jinyu Wang
- Medical Records and Statistics Department, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiaoqing Xu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jun Luo
- Department of Interventional Radiology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Lei Zhang
- Radiology Department, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Cong Luo
- Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jieer Ying
- Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jingjing Li
- Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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10
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Xue S, Song G, Zhu Y, Zhang N, Tan Y. The efficacy and safety of VEGF/VEGFR inhibitors in patients with recurrent or metastatic nasopharyngeal carcinoma: A meta-analysis. Oral Oncol 2022; 135:106231. [PMID: 36327674 DOI: 10.1016/j.oraloncology.2022.106231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/20/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022]
Abstract
OBJECTIVES Molecular targeted therapies against vascular endothelial growth factor (VEGF) receptor (VEGFR) have been explored in the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). We conducted a meta-analysis to evaluate the efficacy and safety of VEGF/VEGFR inhibitors for treating rmNPC. MATERIALS AND METHODS Electronic databases were searched for eligible literature. Data on the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), PFS rate, OS rate, and drug-related adverse events (AEs) were extracted. RESULTS A total of 10 studies (published in 9 articles) that involved 357 patients were included. The pooled ORR was 37 % (95 % confidence interval [CI]: 17-60 %), the DCR was 70 % (95 % CI: 51-85 %), the mPFS was 5.69 months (95 % CI: 4.52-6.86), the mOS was 12.61 months (95 % CI: 10.23-14.99), the 1-year PFS rate was 34 % (95 % CI: 25-44 %), and the 1-year OS rate was 62 % (95 % CI: 38-83 %). The pooled incidence of grade 3/4 drug-related AEs was 27 %, while that of grade 5 AEs was 0.22 %. Further subgroup analysis showed that the pooled ORR and DCR for first-line VEGF inhibitors were 80 % (95 % CI: 74-86 %) and 94 % (CI: 82-100 %), respectively. CONCLUSION Our meta-analysis is the first report to demonstrate the efficacy and safety of VEGF/VEGFR inhibitors in patients with rmNPC. Targeting VEGF/VEGFR therapy added to first-line chemotherapy achieved an excellent ORR and DCR, while the improvement in response rates did not translate to a prominent OS benefit.
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Affiliation(s)
- Song Xue
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Ge Song
- Department of Oncology, Shandong Provincial Maternal and Child Health Care Hospital, Jinan 250014, China
| | - Yingming Zhu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Nianping Zhang
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Ying Tan
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
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11
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The Role of CT-Angiography in the Acute Gastrointestinal Bleeding: A Pictorial Essay of Active and Obscure Findings. Tomography 2022; 8:2369-2402. [PMID: 36287797 PMCID: PMC9606936 DOI: 10.3390/tomography8050198] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 09/09/2022] [Accepted: 09/14/2022] [Indexed: 11/16/2022] Open
Abstract
Gastrointestinal bleeding is a potentially life-threatening abdominal emergency that remains a common cause of hospitalisation. Although 80–85% of cases of gastrointestinal bleeding resolve spontaneously, it can result in massive haemorrhage and death. The presentation of gastrointestinal bleeding can range from asymptomatic or mildly ill patients requiring only conservative treatments to severely ill patients requiring immediate intervention. Identifying the source of the bleeding can be difficult due to the wide range of potential causes, the length of the gastrointestinal tract and the intermittent nature of the bleeding. The diagnostic and therapeutic approach is fully dependent on the nature of the bleeding and the patient’s haemodynamic status. Radiologists should be aware of the appropriate uses of computed tomography angiography and other imaging modalities in patients with acute gastrointestinal bleeding, as well as the semiotics of bleeding and diagnostic pitfalls in order to appropriately diagnose and manage these patients. The learning objective of this review is to illustrate the computed tomography angiography technique, including the potential role of dual-energy computed tomography angiography, also highlighting the tips and tricks to identify the most common and uncommon features of acute gastrointestinal bleeding and its obscure form.
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12
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Shijubou N, Sawai T, Hatakeyama T, Munakata S, Yamazoe M. Alveolar Hemorrhage Caused by the Combination of Immune Checkpoint Inhibitors (ICIs) and Angiogenesis Inhibitors: The Underlying Long-Term Vascular Endothelial Growth Factor (VEGF) Inhibition. Cureus 2022; 14:e23272. [PMID: 35449623 PMCID: PMC9012575 DOI: 10.7759/cureus.23272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2022] [Indexed: 11/16/2022] Open
Abstract
The combination of immune checkpoint inhibitors (ICIs) and other anticancer agents is the standard of care for various cancers. Bevacizumab, an anti-angiogenesis inhibitor, causes serious adverse events such as pulmonary hemorrhage (PH). Here, we present a case of drug-induced diffuse alveolar hemorrhage (DAH), an adverse event, in a patient with hepatocellular carcinoma who was treated with a combination of ICIs and anti-angiogenesis inhibitors after long-term use of lenvatinib, which inhibits vascular endothelial growth factor (VEGF). An 85-year-old man with hepatocellular carcinoma initially received lenvatinib, a multi-kinase inhibitor, but the drug was later switched to bevacizumab-atezolizumab combination therapy owing to disease progression. After five cycles, he developed dyspnea and diffuse ground-glass opacities, which improved with discontinuation of the combination therapy and initiation of steroid pulse therapy. Our case findings indicate that both ICIs and anti-angiogenesis inhibitors cause drug-induced DAH, and their combination may increase the severity of DAH. Moreover, long-term VEGF inhibition may induce the development of DAH. Clinicians need to be aware that long-term VEGF inhibition may be associated with DAH and should consider the risk management of such adverse events while using this combination therapy.
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13
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Iba T, Levy JH, Levi M. Viral-induced inflammatory coagulation disorders: Preparing for another epidemic. Thromb Haemost 2021; 122:8-19. [PMID: 34331297 PMCID: PMC8763450 DOI: 10.1055/a-1562-7599] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A number of viral infectious diseases have emerged or reemerged from wildlife vectors that have generated serious threats to global health. Increased international traveling and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The Coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as Dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. Among the various threats, this review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared to viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.
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Affiliation(s)
- Toshiaki Iba
- Emergency and Disaster Medicine, Juntendo University, Bunkyo-ku, Japan
| | - J H Levy
- Anesthesiology and Critcal Care, Duke University, Durham, United States
| | - Marcel Levi
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
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14
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Grechukhina KS, Chebotareva NV, Zhukova LG, Krasnova TN. Clinical and laboratory signs and risk factors for nephrotoxicity, associated with antiangiogenic drugs. TERAPEVT ARKH 2021; 93:661-666. [DOI: 10.26442/00403660.2021.06.200879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 07/09/2021] [Indexed: 11/22/2022]
Abstract
Background. Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy.
Aim. To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs.
Materials and methods. The study included 50 patients who received antiangiogenic drugs in different regimens of chemotherapy. Demographic factors, body mass index, blood pressure levels, type of antiangiogenic drug, and concomitant therapy were assessed. Before treatment and over a period of 8 weeks, the levels of hemoglobin, number of platelets and schistocytes, D-dimer levels, serum lactate dehydrogenase (LDH) levels, as well as daily proteinuria and serum creatinine and eGFRCKD-EPI were assessed. Linear regression analysis was performed to assess risk factors for nephrotoxicity and arterial hypertension (AH).
Results. The median age of patients was 46 [3457] years, 22 (44%) men and 28 (56%) women. AH developed in 52%, a decrease in eGFR in 42%, along with a decrease in hemoglobin levels and an increase in LDH levels at 2 weeks of therapy. The numbers of schistocytes and platelets significantly decreased by 8 weeks of therapy. Risk factors for impaired renal function during treatment with antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1.73 m2, an increase in D-dimer levels, and a decrease in hemoglobin levels by 8 weeks of treatment. The risk factors for AH during therapy were the initial decrease in eGFR less than 80 ml/min/1.73 m2 and no prophylactic anticoagulant therapy.
Conclusion. Early signs of nephrotoxicity of antiangiogenic anticancer drugs were a decrease in eGFR and AH. The independent risk factors for nephrotoxicity were the initial decrease in eGFR, an increase in D-dimer levels, and a decrease in hemoglobin levels at 8 weeks of treatment, while the prophylactic use of anticoagulant therapy reduced this risk in our study.
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15
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Shahik SM, Salauddin A, Hossain MS, Noyon SH, Moin AT, Mizan S, Raza MT. Screening of novel alkaloid inhibitors for vascular endothelial growth factor in cancer cells: an integrated computational approach. Genomics Inform 2021; 19:e6. [PMID: 33840170 PMCID: PMC8042301 DOI: 10.5808/gi.20068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/11/2021] [Indexed: 12/26/2022] Open
Abstract
Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high-resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.
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Affiliation(s)
- Shah Md Shahik
- Molecular Biology Department, AFC Agro Biotech Ltd., Dhaka 1212, Bangladesh.,Bioinformatics Division, Disease Biology and Molecular Epidemiology Research Group (dBme), Chattogram 4202, Bangladesh
| | - Asma Salauddin
- Bioinformatics Division, Disease Biology and Molecular Epidemiology Research Group (dBme), Chattogram 4202, Bangladesh.,Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Md Shakhawat Hossain
- Bioinformatics Division, Disease Biology and Molecular Epidemiology Research Group (dBme), Chattogram 4202, Bangladesh.,Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Sajjad Hossain Noyon
- Bioinformatics Division, Disease Biology and Molecular Epidemiology Research Group (dBme), Chattogram 4202, Bangladesh.,Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Abu Tayab Moin
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Shagufta Mizan
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Md Thosif Raza
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
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16
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Chen S, Sun J, Zhao L, Sun Y, Jia D, Song Y, Luo J, Lei H, Liu N. Safety of apatinib plus S-1 for advanced solid tumor as palliative treatment. Exp Ther Med 2021; 21:62. [PMID: 33365062 PMCID: PMC7716638 DOI: 10.3892/etm.2020.9494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 07/07/2020] [Indexed: 11/12/2022] Open
Abstract
The aim of the present study was to explore the safety of apatinib plus S-1 in treating advanced solid tumors after failure of two or more lines of chemotherapy. A total of 33 patients with advanced cancer treated between April 2016 to March 2019 were retrospectively analyzed. Of these, 13 patients had non-small cell lung cancer (NSCLC), 13 patients had SCLC, 4 patients had esophageal cancer and 3 had cervical cancer. All patients were treated with apatinib 250 mg once daily combined with S-1 60 mg/m2 twice daily for 14 days, repeated every 3 weeks. Adverse reactions were observed until aggravation of adverse reactions beyond the tolerable range or disease progression, and the survival rate and clinical benefits were calculated. The results suggested that the incidence rate of adverse effects (grade 3-4) was 45.5% (15/33). The top three severe adverse effects were hypertension (15.2%), thrombocytopenia (12.1%) and proteinuria (9.1%). A total of 2 patients with lung squamous-cell carcinomas died of severe pulmonary hemorrhage. Other adverse reactions were tolerated in the cohort. A total of 10 patients achieved partial response and the objective response rate was 30.3%. Furthermore, 13 patients achieved stable disease and 10 patients had progressive disease, and accordingly, the disease control rate was 72.7%. In conclusion, apatinib plus S-1 for advanced solid tumor patients as palliative treatment have a certain efficacy and was relatively safe but should be used with caution in patients with squamous-cell lung carcinoma and the efficacy and safety requires further assessment.
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Affiliation(s)
- Siying Chen
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Jifeng Sun
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Yunguang Sun
- Department of Pathology, Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA
| | - Dan Jia
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
| | - Yongchun Song
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Jing Luo
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Hailong Lei
- Department of Radiation Oncology, The People's Hospital of Wuhai Inner Mongolia, Wuhai, Inner Mongolia 016000, P.R. China
| | - Ningbo Liu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer/Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
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17
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Abstract
Cancer therapies can lead to a broad spectrum of cardiovascular complications. Among these, cardiotoxicities remain of prime concern, but vascular toxicities have emerged as the second most common group. The range of cancer therapies with a vascular toxicity profile and the clinical spectrum of vascular toxic effects are quite broad. Historically, venous thromboembolism has received the greatest attention but, over the past decade, the arterial toxic effects, which can present as acute vasospasm, acute thrombosis and accelerated atherosclerosis, of cancer therapies have gained greater recognition. This Review focuses on these types of cancer therapy-related arterial toxicity, including their mechanisms, and provides an update on venous thromboembolism and pulmonary hypertension associated with cancer therapies. Recommendations for the screening, treatment and prevention of vascular toxic effects of cancer therapies are outlined in the context of available evidence and society guidelines and consensus statements. The shift towards greater awareness of the vascular toxic effects of cancer therapies has further unveiled the urgent needs in this area in terms of defining best clinical practices. Well-designed and well-conducted clinical studies and registries are needed to more precisely define the incidence rates, risk factors, primary and secondary modes of prevention, and best treatment modalities for vascular toxicities related to cancer therapies. These efforts should be complemented by preclinical studies to outline the pathophysiological concepts that can be translated into the clinic and to identify drugs with vascular toxicity potential even before their widespread clinical use.
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Affiliation(s)
- Joerg Herrmann
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
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18
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Murakami Y, Kenjo M, Ishikawa K, Sakayauchi T, Itasaka S, Negoro Y, Jingu K, Nishimura Y, Nagata Y, Ogawa K. Risk factors for severe gastrointestinal toxicity in patients receiving palliative radiotherapy for metastatic bone tumors: association with the use of molecular-targeted agents. JOURNAL OF RADIATION RESEARCH 2020; 61:629-634. [PMID: 32567666 PMCID: PMC7336816 DOI: 10.1093/jrr/rraa035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/18/2020] [Indexed: 06/11/2023]
Abstract
This study aimed to investigate whether the use of molecular-targeted agents could affect gastrointestinal (GI) toxicity in palliative radiotherapy (RT) for metastatic bone tumors in the abdominopelvic region. We collected data of patients who received palliative RT for bone metastases in the abdominopelvic region between 2013 and 2014 from six institutions. Data of 395 patients were collected and184 patients received molecularly targeted therapy, of whom 80 received vascular endothelial growth factor (VEGF)-targeted agents. For 556 lesions, 410 sessions of irradiation were undergone. GI toxicity of ≥G3 was observed in 3.8% of patients. The incidence rates of ≥G3 GI toxicity in patients without targeted agents use, in those using VEGF-targeted agents and in those using non-VEGF-targeted agents were 3.8, 7.5 and 1.0%, respectively. Regarding risk factors of the occurrence of ≥G3 GI toxicity, univariate analysis in all patients showed that a history of abdominopelvic surgery was a significant risk factor (P = 0.01), and the use of VEGF-targeted agents showed a trend of high incidence (P = 0.06). In patients using VEGF-targeted agents, both univariate and multivariate analysis showed that combined anticoagulant use (P = 0.03 and 0.01) and agent use between 1 week before and after RT (P = 0.046 and 0.03) were significant risk factors. In conclusion, the history of abdominopelvic surgery was associated with ≥G3 GI toxicity and the use of VEGF-targeted agents showed a trend for high incidence. When using VEGF-targeted agents, caution should be exercised in the combined use of anticoagulants and in the agent use between 1 week before and after RT.
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Affiliation(s)
- Yuji Murakami
- Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Masahiro Kenjo
- Hiroshima High-Precision Radiotherapy Cancer Center, Hiroshima, Japan
| | - Kazuki Ishikawa
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Toru Sakayauchi
- Department of Radiation Oncology, Osaki Citizen Hospital, Osaki, Japan
| | - Satoshi Itasaka
- Department of Radiation Oncology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Yoshiharu Negoro
- Department of Radiation Oncology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Keiichi Jingu
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yasumasa Nishimura
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Yasushi Nagata
- Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Kazuhiko Ogawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Wang P, Zhao H, Zhao Q, Ren F, Shi R, Liu X, Liu J, Liu H, Chen G, Chen J. Risk Factors and Clinical Significance of D-Dimer in the Development of Postoperative Venous Thrombosis in Patients with Lung Tumor. Cancer Manag Res 2020; 12:5169-5179. [PMID: 32636679 PMCID: PMC7335272 DOI: 10.2147/cmar.s256484] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The incidence of venous thromboembolism (VTE) is higher in patients with lung cancer. The aim of this study was to investigate the risk factors associated with postoperative VTE and explore the VTE predication capacity of D-dimer kinetics. PATIENTS AND METHODS Six hundred patients who had lung tumor surgery were analyzed retrospectively between January 2018 and August 2019, and venous ultrasound imaging and D-dimer examination before and after surgery were recommended to all operative patients. Of these 600 patients, 523 patients had venous thromboembolism after surgery, and 77 patients had not found. The general clinical data, postoperative prophylactic anticoagulant therapy, early systemic thromboprophylaxis, 50% increment of D-dimer, 100% increment of D-dimer, and perioperative (preoperative and days 1, 3, and 5 after surgery) D-dimer levels were collected. Logistic regression analysis was used to analyze the independent risk factors of postoperative VTE. RESULTS VTE developed in 77 (12.8%) patients. In a univariate analysis, age, surgical approach, tumor size, histology, postoperative preventive anticoagulation, postoperative limb compression therapy, postoperative hemostasis, duration of operation, early systemic thromboprophylaxis, 100% increment of D-dimer, preoperative and postoperative D-dimer level, intraoperative blood loss, and time spent in the hospital were significantly different between the thrombus group and nonthrombus group (P < 0.05). Multivariate analysis showed that age >60 years (P = 0.006) and D-dimer level on 5 days after surgery (P = 0.000) were significant independent risk factors for VTE. Postoperative D-dimer was significantly higher than the preoperative level (P < 0.001). Postoperative D-dimer level was significantly different between benign and malignant tumor groups (P < 0.05) and between the thrombus group and nonthrombus group (P < 0.001). Preventive anticoagulation and limb compression therapy starting from the first day after surgery was statistically significant between the thrombus group and the nonthrombus group (P < 0.05). CONCLUSION Continuous detection of D-dimer level after pulmonary tumor surgery combined with thrombotic-related risk factors can better evaluate the occurrence of VTE. Preventive anticoagulant therapy and limb compression therapy starting from the first day after surgery can effectively reduce the incidence of VTE.
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Affiliation(s)
- Pan Wang
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Honglin Zhao
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Qingchun Zhao
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Fan Ren
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Ruifeng Shi
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Xingyu Liu
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Jinghao Liu
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Hongyu Liu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Gang Chen
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Jun Chen
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
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Jeon HL, Byun SJ, Pratt NL, Sultana J, Park SJ, Shin JY. Cardiovascular risk in patients receiving ranibizumab for exudative age-related macular degeneration: a nationwide self-controlled case-series study. Br J Ophthalmol 2020; 105:543-548. [PMID: 32522792 DOI: 10.1136/bjophthalmol-2020-316373] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/07/2020] [Accepted: 05/11/2020] [Indexed: 11/03/2022]
Abstract
AIMS To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD). METHODS We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately. RESULTS Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI. CONCLUSIONS Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.
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Affiliation(s)
- Ha-Lim Jeon
- School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea
| | - Seong Jun Byun
- School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.,Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nicole L Pratt
- Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - Janet Sultana
- Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Sicily, Italy
| | - Sang Jun Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea
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Dai H, Liu C, Li P, Mai Z, Tan X, Chen S, Zhou Z, Tang Z, Miao J, Liu L, Fang Y. Risk of Dyslipidemia Associated with VEGF/VEGFR Inhibitors: A Meta-Analysis. Transl Oncol 2020; 13:100779. [PMID: 32375082 PMCID: PMC7205761 DOI: 10.1016/j.tranon.2020.100779] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 04/02/2020] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE This meta-analysis was performed to investigate hyperlipidemia in patients with carcinoma treated with vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors. METHODS We searched for eligible phase II and III studies using PubMed and Embase databases. We then summarized reported occurrences of hyperlipidemia in patients with different cancers. Relative risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by Revman 5 software in meta-analysis. RESULTS Eleven trials (4760 subjects) were included in this meta-analysis. Overall, VEGF/VEGFR inhibitors had similar incidence of hypertriglyceridemia (RR = 0.56, 95% CI = 0.24%-1.32%, P = .19), hypercholesterolemia (RR = 1.15, 95% CI = 0.42%-3.16%, P = .78), and LDL elevation (RR = 4.58, 95% CI = 0.80%-26.25%, P = .09) than control drugs, under high heterogeneity. Moreover, subgroup analyses found VEGF/VEGFR inhibitors had higher incidence of hypertriglyceridemia (RR = 1.86, 95% CI = 1.37%-2.52%, P < .001) and hypercholesterolemia (RR = 2.95, 95% CI = 2.02%-4.30%, P = .006) than blank control or placebo control drugs (placebo-controlled-group), although with lower incidence of hypertriglyceridemia (RR = 0.29, 95% CI = 0.12%-0.69%, P < .001) and hypercholesterolemia (RR = 0.39, 95% CI = 0.28%-0.56%, P < .001) than positive control drugs (positive-controlled-groups). CONCLUSION The use of VEGF/VEGFR inhibitors, especially the multitargeted VEGFR tyrosine kinase inhibitors (VEGFR-TKIs), was associated with higher risk of hyperlipidemia than the use of placebo, but this risk was less than that associated with mTOR or FGFR inhibitors. It indicated that clinicians need to pay close attention to the occurrence of hyperlipidemia in VEGFR-TKIs therapies.
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Affiliation(s)
- Huihui Dai
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Chang Liu
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Peijuan Li
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Zhangfeng Mai
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Xiaoming Tan
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Sijing Chen
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Ziling Zhou
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Zhiben Tang
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Jingwei Miao
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518
| | - Lizhong Liu
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518.
| | - Yi Fang
- Phase I Clinical Research Unit, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, No. B24, Yinquan road, Qingcheng district, Qingyuan city, Guangdong Province, China 511518; Department of Pharmacy, Peking University People's Hospital, Beijing, China. 100034.
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Furuya-Kanamori L, Doi SA, Onitilo A, Akhtar S. Is there truly an increase in risk of cardiovascular and hematological adverse events with vascular endothelial growth factor receptor tyrosine kinase inhibitors? Expert Opin Drug Saf 2019; 19:223-228. [PMID: 31698959 DOI: 10.1080/14740338.2020.1691167] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Objectives: Recent studies have shown an increase risk of cardiovascular and hematological adverse events associated with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). The authors hypothesize that the original studies may have produced exaggerated results because of the small baseline risks involved.Methods: A meta-analysis that included 71 trials, 8 different VEGFR-TKIs, and 11 adverse events were re-analyzed. The outcome of interest was re-defined as the complementary outcome (i.e. remaining free of an adverse event). The inverse variance heterogeneity model was used to pool the effect size.Results: VEGFR-TKIs decreased the risk of remaining free of hypertension by 7% (RR 0.93; 95%CI:0.88-0.97). Specific VEGFR-TKIs; pazopanib, regorafenib, and nintedanib were associated with a decrease risk of remaining free of an arterial thrombotic event (RR 0.96; 95%CI:0.93-0.99), thrombocytopenia (RR 0.91; 95%CI:0.89-0.93), and bleeding (RR 0.96; 95%CI:0.93-0.99) respectively. VEGFR-TKIs were not associated with the thrombotic event, myocardial infarction, stroke, venous thrombotic event, pulmonary embolism, left ventricular dysfunction, or QTc interval prolongation.Conclusion: VEGFR-TKIs are associated with a small increase in the risk of patients developing hypertension, arterial thrombotic events, thrombocytopenia, and bleeding. Previous studies overestimated the actual risk associated with VEGFR-TKIs by analyzing the outcome with the lower baseline risk.
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Affiliation(s)
- Luis Furuya-Kanamori
- Research School of Population Health, ANU College of Health and Medicine, Australian National University, Acton, Australia
| | - Suhail Ar Doi
- Department of Population Medicine, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Adedayo Onitilo
- Department of Hematology/Oncology, Marshfield Clinic, Weston, WI, USA
| | - Saghir Akhtar
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
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Lee I, Adimadhyam S, Nutescu EA, Zhou J, Asfaw AA, Sweiss K, Patel PR, Calip GS. Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study. Pharmacotherapy 2019; 39:921-928. [PMID: 31332810 PMCID: PMC7395667 DOI: 10.1002/phar.2310] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
STUDY OBJECTIVE Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S. POPULATION DESIGN Nested case-control study. DATA SOURCE Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015). PATIENTS A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case. MEASUREMENTS AND MAIN RESULTS Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75). CONCLUSION We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.
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Affiliation(s)
- Inyoung Lee
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
| | - Sruthi Adimadhyam
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
| | - Edith A. Nutescu
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
- Center for Pharmacoepidemiology & Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL
| | - Jifang Zhou
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
| | - Alemseged A. Asfaw
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
| | - Karen Sweiss
- Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
| | - Pritesh R. Patel
- Division of Hematology Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL
| | - Gregory S. Calip
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
- Center for Pharmacoepidemiology & Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL
- Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA
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Raza S, Ergun SB, Toklu Y, Cakmak HB, Ipek A, Cagil N. Evaluating the Effect of Intravitreal Ranibizumab on Retrobulbar Hemodynamics by Color Doppler Ultrasonography in Neovascular AMD. Ophthalmic Surg Lasers Imaging Retina 2019; 50:437-443. [DOI: 10.3928/23258160-20190703-05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 01/17/2019] [Indexed: 11/20/2022]
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Kobat SG, Celiker FU, Dagli AF, Kasar K. The effect on wound healing of pazopanib and bevacizumab compared with corticosteroid in experimental glaucoma filtration surgery. Int J Ophthalmol 2018; 11:1909-1915. [PMID: 30588421 DOI: 10.18240/ijo.2018.12.05] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 08/09/2018] [Indexed: 12/15/2022] Open
Abstract
AIM To compare the effects of bevacizumab and pazopanib with corticosteroids on wound healing after trabeculectomy. METHODS In the study, 35 New Zealand white rabbits were randomly divided into five groups. Apart from the first group, limbus-based trabeculectomy was performed for the eyes of rabbits. No postoperative treatment was administered for group I. Topically administered saline, prednisolone acetate (1%), bevacizumab 5 mg/mL, pazopanib 5 mg/mL for group II, III, IV and V respectively were applied for groups 6h daily for 28d. On day 28 of the experiment, eyes were enucleated and histologically and immunohistochemically analyzed. RESULTS The fibroblast counts of groups IV and V were determined to be lower than those of groups II and III (P<0.05). In the mononuclear cell (MNC) count evaluation, no statistically significant difference was determined between the treatment groups (P>0.05). The immunohistochemical staining intensity of fibroblast growth factor β (FGF-β) and vascular endothelial growth factor (VEGF) was determined to be lower in groups IV and V than in groups II and III (P<0.05). No statistically significant difference was determined between groups IV and V in respect of fibroblast count, MNC count, FGF-β and VEGF staining intensity (P>0.05). The platelet derived growth factor β (PDGF-β) intensity was lower in group V than in groups II, III and IV (P<0.05). While the PDGF-β staining intensity was significantly lower in group IV than in group II, the difference compared with group III was not statistically significant (P>0.05). CONCLUSION Bevacizumab and pazopanib might be good alternatives of corticosteroid treatment on delaying wound healing in glaucoma surgery.
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Affiliation(s)
- Sabiha Gungor Kobat
- Department of Ophthalmology, Elazig Health Sciences University, Elazig 23000, Turkey
| | - Fatma Ulku Celiker
- Department of Ophthalmology, School of Medicine, Firat University, Elazig 23119, Turkey
| | - Adile Ferda Dagli
- Department of Pathology, School of Medicine, Firat University, Elazig 23119, Turkey
| | - Kader Kasar
- Department of Ophthalmology, Ordu State Hospital, Ordu 52100, Turkey
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Xiao B, Wang W, Zhang D. Risk of bleeding associated with antiangiogenic monoclonal antibodies bevacizumab and ramucirumab: a meta-analysis of 85 randomized controlled trials. Onco Targets Ther 2018; 11:5059-5074. [PMID: 30174444 PMCID: PMC6110629 DOI: 10.2147/ott.s166151] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Aim Bevacizumab and ramucirumab are antiangiogenic monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, used in various cancers. Bleeding events have been described with these two agents. We conducted an up-to-date meta-analysis to determine the relative risk (RR) associated with the use of antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab. Methods This meta-analysis of randomized controlled trials was performed after searching PubMed, American Society for Clinical Oncology Abstracts, European Society for Medical Oncology Abstracts, and the proceedings of major conferences for relevant clinical trials. RR and 95% CIs were calculated by random-effects or fixed-effects models for all-grade and high-grade bleeding events related to the angiogenesis inhibitors. Results Eighty-five randomized controlled trials were selected for the meta-analysis, covering 46,630 patients. The results showed that antiangiogenic monoclonal antibodies significantly increased the risk of all-grade (RR: 2.38, 95% CI: 2.09–2.71, p<0.00001) and high-grade (RR: 1.71, 95% CI: 1.48–1.97, p<0.00001) bleeding compared with control arms. In the subgroup analysis, bevacizumab significantly increased the risk of all-grade (RR: 2.73, 95% CI: 2.24–3.33, p<0.00001) and high-grade bleeding (RR: 1.98, 95% CI: 1.68–2.34, p<0.00001), but ramucirumab only increased the risk of all-grade bleeding (RR: 1.94, 95% CI: 1.76–2.13, p<0.00001) and no difference was observed for the risk of high-grade bleeding (RR: 1.04, 95% CI: 0.78–1.39, p=0.79) compared with the control group. For lung cancer patients, bevacizumab significantly increased the risk of all-grade (RR: 4.72, 95% CI: 1.99–11.19, p=0.0004) and high-grade pulmonary hemorrhage (RR: 3.97, 95% CI: 1.70–9.29, p=0.001), but no significant differences in the risk of all-grade (RR: 1.09, 95% CI: 0.76–1.57, p=0.64) and high-grade (RR: 1.22, 95% CI: 0.35–4.21, p=0.75) pulmonary hemorrhage were observed for ramucirumab. The increased risk of all-grade and high-grade bleeding was also observed in colorectal cancer or non-colorectal tumors and low-dose or high-dose angiogenesis inhibitors. Conclusion Antiangiogenic monoclonal antibodies are associated with a significant increase in the risk of all-grade and high-grade bleeding. Ramucirumab may be different from bevacizumab in terms of the risk of high-grade bleeding and the risk of all-grade and high-grade pulmonary hemorrhage in lung cancer patients.
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Affiliation(s)
- Bingkun Xiao
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Weilan Wang
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China,
| | - Dezhi Zhang
- Department of Pharmacy, The 264th Hospital of PLA, Taiyuan, Shanxi, China
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Singh G, Rathi AK, Singh K, Sharma D. Venous thromboembolism in cancer patients - magnitude of problem, approach, and management. Indian J Cancer 2018; 54:308-312. [PMID: 29199711 DOI: 10.4103/ijc.ijc_101_17] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Cancer is hypercoagulable state. Patients with cancer are at high risk to develop venous thromboembolism (VTE). Relative risk of developing VTE is approximately seven times higher in patients with active cancer. The incidence of occult malignancy is 7%-12% in patients with idiopathic deep vein thrombosis (DVT). However, little research has been focused on cancer with thromboembolism. Lowmolecularweight heparin most frequently used pharmacologic agents as recommended by established guidelines. The aim was to evaluate the magnitude of problem in cancer patients and treatment option as per established guidelines. EMBASE, MEDLINE, and PubMed search of the literature were done to evaluate the association of DVT with various malignancy, magnitude of problem, approach, and various guidelines for the management of DVT. References of all publication were also searched to enrich this article for recent update. Thromboprophylaxis in cancer patient is gray zone area. This need lot of investigational work to find highrisk patients who would benefit from primary thromboprophylaxis.
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Affiliation(s)
- G Singh
- Department of Radiotherapy, VMMC and Safdarjung Hospital, New Delhi, India
| | - A K Rathi
- Department of Radiotherapy, Maulana Azad Medical College, New Delhi, India
| | - K Singh
- Department of Radiotherapy, Maulana Azad Medical College, New Delhi, India
| | - D Sharma
- Department of Radiotherapy, VMMC and Safdarjung Hospital, New Delhi, India
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Kuk A, Magnowska M, Suchy W, Swierczynska J, Zaborowski MP, Gaca M, Nowak-Markwitz E. Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab. Target Oncol 2018; 12:495-503. [PMID: 28580507 PMCID: PMC5524869 DOI: 10.1007/s11523-017-0496-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab. Objective The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events. Patients and Methods Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events. Results Only patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity. Conclusions An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.![]()
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Affiliation(s)
- Anna Kuk
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland.
| | - Magdalena Magnowska
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
| | - Wiktor Suchy
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
| | - Joanna Swierczynska
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
| | - Mikolaj Piotr Zaborowski
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
| | - Michal Gaca
- Department of Anesthesiology in Obstetrics and Gynecology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
| | - Ewa Nowak-Markwitz
- Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, ul.Polna 33, 60-535, Poznan, Poland
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Li ZY, Fan XX, Wang YJ, Yao K, Liu ZW, Pan WT, Ye YL, Yang P, Huang YC, Wu ZM, Zhou FJ. Metastatic renal cell carcinoma: the first report of unilateral fundus hemorrhage induced by sorafenib. Oncotarget 2018; 7:35181-7. [PMID: 27174916 PMCID: PMC5085219 DOI: 10.18632/oncotarget.9285] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/28/2016] [Indexed: 12/21/2022] Open
Abstract
Background Renal cell carcinoma (RCC) is the most common type of kidney tumor with increasing incidence. Tyrosine Kinase Inhibitors (TKIs) are considered important treatment in the management of metastatic RCC. Some previous studies demonstrated that sorafenib treatment is associated with a significantly increased risk of potentially life-threatening adverse events, like bleeding. But bleeding at the fundus site is the rarest type of hemorrhage. As for TKIs' risk of bleeding, how we distinguish the degree of bleeding and what optimal strategies should we take to manage bleeding, needs to be studied systematically. Results With a long-term exposure (17 months) to sorafenib, he experienced blurred vision in his right eye and was hospitalized. The patient's diagnosis was central retinal vein occlusion (CRVO) of the right eye. Unfortunately sorafenib was terminated. Materials and Methods The authors describe the first case of unilateral fundus hemorrhage induced by sorafenib. A 42-year-old man was diagnosed metastatic left RCC, with clinical stage and prognostic risk being assessed as T4N1M1 and intermediate. He received a radical left nephrectomy and retroperitoneal lymph node dissection, with taking the oral multi-targeted TKI, sorafenib (800 mg daily) from 7 months to 7 days before the surgery and 7 days after the surgery restarting again until the occurrence of fundus hemorrhage. Conclusions In this patient, long-term exposure to sorafenib possibly has increased the risk of fundus hemorrhage. This article provides us a previously undescribed morbidity associated with sorafenib, which reminds us of understanding the risk of bleeding and how this complication might be managed systematically.
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Affiliation(s)
- Zhi Yong Li
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xin Xiang Fan
- Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Yan Jun Wang
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Kai Yao
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhuo Wei Liu
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wen Tao Pan
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yun Lin Ye
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ping Yang
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yi Chuan Huang
- Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Zhi Ming Wu
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Fang Jian Zhou
- State Key Laboratory of Oncology in Southern China, Guangzhou, China.,Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Kim JH, Kim JE, Hong YS, Kim SY, Kim KP, Choi KE, Shin JH, Kim TW. Increased incidence of chemoport-related thrombosis in patients with colorectal cancer receiving bevacizumab: A single-institutional experience. Chin J Cancer Res 2018; 30:460-467. [PMID: 30210226 PMCID: PMC6129570 DOI: 10.21147/j.issn.1000-9604.2018.04.09] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective Chemoport-related thrombosis (CRT) is a serious complication that causes morbidities and interrupts administration of intravenous cancer therapy. We investigated the incidence and risk of CRT in colorectal cancer (CRC) patients treated with bevacizumab (BEV). Methods We retrospectively reviewed 1,534 CRC patients who received chemotherapy with or without BEV using a chemoport between 2014 and 2016. Results The participants had a median age of 58 (18−85) years, and 60.3% were male. All participants were stratified into three groups: adjuvant chemotherapy (AC) (n=670), palliative chemotherapy (PC) without BEV (n=356), and PC with BEV (n=508). The median follow-up was 20.19 (interquartile range, 14.07−27.19) months. CRT occurred in 3.8% of all patients; incidence of symptomatic and asymptomatic CRT was 2.9% and 0.9%, respectively. CRT occurred more in patients with BEV (5.7%) than in patients without BEV (2.9%, P=0.008). The cumulative incidence of CRT in patients administered PC with BEV was significantly higher than that in those administered AC (P=0.011) and there was a trend toward increased CRT in patients administered PC with BEV compared with those administered PC without BEV (P=0.044). Multivariate analysis found that BEV treatment was the only variable that was significantly associated with CRT (hazard ratio, 2.06; 95% confidence interval, 1.24−3.43; P=0.006). Conclusions BEV treatment was significantly associated with increased incidence of CRT in CRC patients.
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Affiliation(s)
- Jwa Hoon Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Jeong Eun Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Yong Sang Hong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Sun Young Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Ki Eun Choi
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Ji Hoon Shin
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
| | - Tae Won Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea
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31
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Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J, Beckman JA, Harrison DG, Moslehi J. Mechanisms of VEGF (Vascular Endothelial Growth Factor) Inhibitor-Associated Hypertension and Vascular Disease. Hypertension 2017; 71:e1-e8. [PMID: 29279311 DOI: 10.1161/hypertensionaha.117.10271] [Citation(s) in RCA: 195] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Arvind K Pandey
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Eric K Singhi
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Juan Pablo Arroyo
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Talat Alp Ikizler
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Edward R Gould
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Jonathan Brown
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Joshua A Beckman
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - David G Harrison
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Javid Moslehi
- From the Division of Cardiovascular Medicine (A.K.P., E.K.S., J.B., J.A.B., J.M.), Division of Nephrology (J.P.A., T.A.I., E.R.G.), Vanderbilt Center for Kidney Disease (T.A.I.), Division of Clinical Pharmacology (D.G.H.) and Cardio-Oncology Program (J.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
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32
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Nishino M, Hatabu H, Sholl LM, Ramaiya NH. Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care. Radiographics 2017; 37:1371-1387. [PMID: 28898185 DOI: 10.1148/rg.2017170015] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Recent advances in understanding the molecular mechanisms of cancer have opened a new era of precision medicine for cancer treatment. Precision cancer therapies target specific molecules that are responsible for cancer development and progression, and they achieve marked treatment benefits in specific cohorts of patients. However, these therapies are also associated with a variety of complications that are often unique to specific groups of anticancer agents. The rapidly increasing use of immune checkpoint inhibitors in the treatment of various advanced malignancies has brought new challenges in diagnosing and monitoring a unique set of toxic effects termed immune-related adverse events. Familiarity with cutting-edge cancer treatment approaches and awareness of the emerging complications from novel therapies are essential for radiologists, who play a key role in the care of patients with cancer. This article provides a comprehensive review of the thoracic complications of precision cancer therapies, describes their imaging features and clinical characteristics, and discusses the role of radiologists in the diagnosis and monitoring of these entities. The authors also address the molecular mechanisms of anticancer agents that relate to thoracic complications and emphasize emerging challenges in novel cancer therapies. This article is designed to serve as a practical reference guide for day-to-day practice for radiologists in the era of precision cancer medicine. ©RSNA, 2017.
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Affiliation(s)
- Mizuki Nishino
- From the Departments of Radiology (M.N., H.H., N.H.R.) and Pathology (L.M.S.), Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215
| | - Hiroto Hatabu
- From the Departments of Radiology (M.N., H.H., N.H.R.) and Pathology (L.M.S.), Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215
| | - Lynette M Sholl
- From the Departments of Radiology (M.N., H.H., N.H.R.) and Pathology (L.M.S.), Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215
| | - Nikhil H Ramaiya
- From the Departments of Radiology (M.N., H.H., N.H.R.) and Pathology (L.M.S.), Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215
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Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol 2017; 70:2536-2551. [PMID: 29145954 PMCID: PMC5825187 DOI: 10.1016/j.jacc.2017.09.1096] [Citation(s) in RCA: 260] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 09/24/2017] [Accepted: 09/26/2017] [Indexed: 12/27/2022]
Abstract
Modern cancer therapy has successfully cured many cancers and converted a terminal illness into a chronic disease. Because cancer patients often have coexisting heart diseases, expert advice from cardiologists will improve clinical outcome. In addition, cancer therapy can also cause myocardial damage, induce endothelial dysfunction, and alter cardiac conduction. Thus, it is important for practicing cardiologists to be knowledgeable about the diagnosis, prevention, and management of the cardiovascular complications of cancer therapy. In this first part of a 2-part review, we will review cancer therapy-induced cardiomyopathy and ischemia. This review is based on a MEDLINE search of published data, published clinical guidelines, and best practices in major cancer centers. With the number of cancer survivors expanding quickly, the time has come for cardiologists to work closely with cancer specialists to prevent and treat cancer therapy-induced cardiovascular complications.
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Affiliation(s)
- Hui-Ming Chang
- Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, Missouri
| | - Rohit Moudgil
- Department of Cardiology, University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Tiziano Scarabelli
- Division of Cardiology, Virginia Common Wealth University, Richmond, Virginia
| | - Tochukwu M Okwuosa
- Division of Cardiology, Rush University Medical Center, Chicago, Illinois
| | - Edward T H Yeh
- Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, Missouri.
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34
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Liu B, Ding F, Zhang D, Wei GH. Risk of venous and arterial thromboembolic events associated with VEGFR-TKIs: a meta-analysis. Cancer Chemother Pharmacol 2017; 80:487-495. [PMID: 28695268 DOI: 10.1007/s00280-017-3386-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 07/05/2017] [Indexed: 10/19/2022]
Abstract
The reported incidence of arterial and venous thromboembolic events varies markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta-analysis to determine the incidence and the relative risk (RR) of venous thromboembolism events (VTEs) and arterial thromboembolic events (ATEs) associated with these agents. Databases (PubMed, Web of Science) were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RRs and 95% confidence intervals (CIs) using either random-effects or fixed-effects models according to the heterogeneity of the included studies. A total of 24,855 patients from 48 studies were included. The overall incidence of all-grade and high-grade VTEs associated with VEGFR-TKIs was 3.6% (95% CI 2.3-5.2%) and 1.6% (95% CI 1.0-2.4%), respectively. The use of VEGFR-TKIs did not significantly increase the risk of developing all-grade (RR 0.91; 95% CI 0.68-1.22; P = 0.558) and high-grade (RR 1.05; 95% CI 0.84-1.31; P = 0.769) VTEs. The overall incidence of all-grade and high-grade ATEs associated with VEGFR-TKIs was 2.7% (95% CI 1.7-3.6%) and 0.6% (95% CI 0.2-1.2%), respectively. The use of VEGFR-TKIs significantly increase the risk of developing all-grade (RR 3.09; 95% CI 1.41-6.76; P = 0.033) ATEs, and a tendency to increase the risk of high-grade (RR 1.49; 95% CI 0.99-2.24; P = 0.101) ATEs was also detected. Patients with cancer that receive VEGFR-TKIs are at high risk of developing ATEs. Physicians should be aware of these adverse effects and should monitor cancer patients receiving VEGFR-TKIs.
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Affiliation(s)
- Bo Liu
- Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China
| | - Fengxia Ding
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2 RD, Yuzhong District, Chongqing, 400014, China. .,Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China.
| | - Deying Zhang
- Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China
| | - Guang-Hui Wei
- Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
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35
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Biliary and pancreatic complications of molecular targeted therapies in cancer imaging. Abdom Radiol (NY) 2017; 42:1721-1733. [PMID: 28160038 DOI: 10.1007/s00261-017-1050-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The purpose of this review is to familiarize radiologists with the different imaging manifestations of biliary and pancreatic toxicity of molecular targeted therapies. The advent of molecular targeted therapies for cancer treatment has prompted radiologists to be familiar with these new molecules, their patterns of response, and their class-specific toxicities. While liver and bowel toxicities have been extensively reported in literature, less is known about the pathogenesis and imaging of toxicity involving the pancreatobiliary system. Biliary and pancreatic toxicity of molecular targeted therapies present with variable manifestations and varying degrees of severity, from asymptomatic liver function tests elevation to acute pancreatitis or cholecystitis. Management of these conditions depends on the clinical scenario and the severity of the findings. In this article, we will (1) present the various classes of molecular targeted therapies most commonly associated with biliary and pancreatic toxicity; (2) illustrate imaging findings of drug-associated biliary and pancreatic injuries and their possible differential diagnosis; and (3) provide a guide for management of these conditions.
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36
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Anti-angiogenetic agents against tumor types and cardiovascular risk. Hellenic J Cardiol 2017; 58:220-222. [DOI: 10.1016/j.hjc.2017.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 06/15/2017] [Indexed: 11/22/2022] Open
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Tian R, Yan H, Zhang F, Sun P, Zheng X, Zhu Y, Wang Q, He J. Incidence and relative risk of hemorrhagic events associated with ramucirumab in cancer patients: a systematic review and meta-analysis. Oncotarget 2016; 7:66182-66191. [PMID: 27507055 PMCID: PMC5323225 DOI: 10.18632/oncotarget.11097] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 07/10/2016] [Indexed: 12/04/2022] Open
Abstract
The purpose of this study was to investigate the overall incidence and relative risk (RR) of hemorrhagic events in cancer patients treated with ramucirumab. 298 potentially relevant citations on ramucirumab from Pubmed, Web of Science and the Cochrane Database, as well as abstracts presented at conferences (all up to March 2016) were identified through our initial search. Only phase II and III prospective clinical trials of ramucirumab among cancer patients with toxicity records on hemorrhagic events were selected for final analysis. Data was extracted from the original studies by two independent reviewers. The overall incidence, RR, and 95% confidence intervals (CI) were calculated using fixed or random effects models according to the heterogeneity of the enrolled studies. The statistical analysis was performed by STATA version 11.0 (Stata Corporation, College Station, TX). 4963 patients with a variety of solid tumors from eleven eligible studies were selected into our analysis. The results demonstrated that the overall incidences of all-grade and high-grade hemorrhagic events in cancer patients were 27.6% (95% CI, 18.7-36.5%) and 2.3% (95% CI, 1.3-3.2%), respectively. The RR of hemorrhagic events of ramucirumab compared to control was significantly increased for low-grade (RR, 2.06; 95% CI, 1.85-2.29, p < 0.001), but not for high-grade (RR, 1.19, 95% CI, 0.80-1.76, p=0.39) hemorrhagic events. Hemorrhagic events associated with ramucirumab are modest and manageable while patients could continue to receive ramucizumab treatment to achieve their maximum clinical benefits.
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Affiliation(s)
- Rui Tian
- Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China
| | - Hong Yan
- Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China
| | - Fei Zhang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
- State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Peng Sun
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
- State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Xucai Zheng
- Department of Head, Neck and Breast Surgery, Anhui Cancer Hospital, Hefei, Anhui, China
| | - Yi Zhu
- Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei, Anhui, China
| | - Qing Wang
- Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei, Anhui, China
| | - Jie He
- Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China
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Systemic safety of intravitreal anti-vascular endothelial growth factor agents in age-related macular degeneration. Curr Opin Ophthalmol 2016; 27:224-43. [PMID: 26871657 DOI: 10.1097/icu.0000000000000257] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
PURPOSE OF REVIEW The purpose of review is to summarize the literature addressing nonocular adverse events in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. RECENT FINDINGS The incidence of overall nonocular serious adverse events varied from 0 to 39.3% and nonocular adverse events ranged from 0 to 86.9%. Few studies have reported a significant association between use of intravitreal anti-VEGF agents and overall incidence of adverse events, stroke, myocardial infarction, nonocular hemorrhage and death, with overall greater concern in patients treated with bevacizumab. Additionally, history of stroke or other arterial thromboembolic event may be a risk factor for future stroke in patients treated with intravitreal anti-VEGF agents. Theories explaining the mechanisms of increased risk of nonocular adverse events secondary to anti-VEGF agent use surround the necessity of VEGF for the normal functioning of the endothelium and the damage incurred with use of anti-VEGF agents. SUMMARY Current data are insufficient to definitively conclude that intravitreal anti-VEGF agents are safe, although there is a trend toward an overall favorable systemic safety profile. Caution should be exerted in patients with a history of cardiovascular disease, as these patients may be at greater risk for nonocular serious adverse events.
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Sundararajan S, Kumar A, Poongkunran M, Kannan A, Vogelzang NJ. Cardiovascular adverse effects of targeted antiangiogenic drugs: mechanisms and management. Future Oncol 2016; 12:1067-80. [DOI: 10.2217/fon.16.4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Anticancer treatment has evolved enormously over the last decade. Drugs targeting receptor tyrosine kinases, VEGFR and EGFR have changed the treatment landscape of certain cancers and have shifted the theme of anticancer therapy toward personalized care. However, these newer agents also come with unique side-effect profiles not seen with conventional chemotherapy including serious cardiovascular adverse effects. Hence, meticulous understanding of the adverse effects is crucial in maximizing clinical benefits and minimizing detrimental effects of these newer drugs. We have reviewed the cardiovascular adverse effects of anti-VEGF therapy in this article.
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Affiliation(s)
- Srinath Sundararajan
- Division of Hematology & Oncology, Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Abhijeet Kumar
- Division of Hematology & Oncology, Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Mugilan Poongkunran
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Arun Kannan
- Division of Cardiology, Department of Medicine, University of Arizona, Tucson, AZ, USA
| | - Nicholas J Vogelzang
- University of Nevada School of Medicine & US Oncology/Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
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Moudgil R, Yeh ETH. Mechanisms of Cardiotoxicity of Cancer Chemotherapeutic Agents: Cardiomyopathy and Beyond. Can J Cardiol 2016; 32:863-870.e5. [PMID: 27117975 DOI: 10.1016/j.cjca.2016.01.027] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 01/26/2016] [Accepted: 01/27/2016] [Indexed: 12/14/2022] Open
Abstract
Tremendous strides have been made in the treatment of various oncological diseases such that patients are surviving longer and are having better quality of life. However, the success has been tainted by the iatrogenic cardiac toxicities. This is especially concerning in the younger population who are facing cardiac disease such as heart failure in their 30s and 40s as the consequence of the anthracycline's side effects (used for childhood leukemia and lymphoma). This resulted in the awareness of cardiotoxic effects of anticancer drugs and emergence of a new discipline: oncocardiology. Since then, numerous anticancer drugs have been correlated to cardiomyopathy. Additionally, other cardiovascular effects have been identified, which includes but is not limited to myocardial infarction, thrombosis, hypertension, arrhythmias, and pulmonary hypertension. In this review we examine some of the anticancer agents that mitigate cardiotoxicity and present current knowledge of molecular mechanism(s). The aim of the review is to ignite awareness of emerging cardiotoxic effects as new generations of anticancer agents are being tested in clinical trials and introduced as part of the therapeutic armamentarium to our oncological patients.
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Affiliation(s)
- Rohit Moudgil
- Department of Cardiology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
| | - Edward T H Yeh
- Department of Cardiology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.
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41
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Liu S, Kurzrock R. Understanding Toxicities of Targeted Agents: Implications for Anti-tumor Activity and Management. Semin Oncol 2015; 42:863-75. [DOI: 10.1053/j.seminoncol.2015.09.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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42
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Abdel-Rahman O, ElHalawani H. Risk of hematological toxicities in patients with solid tumors treated with ramucirumab: a meta-analysis. Future Oncol 2015; 11:2949-61. [PMID: 26422782 DOI: 10.2217/fon.15.178] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND We performed a meta-analysis of the risk of hematological adverse events associated with ramucirumab. METHODS Eligible studies included randomized Phase II and III trials of patients with solid tumors on ramucirumab, describing events of anemia, leucopenia, neutropenia, febrile neutropenia and thrombocytopenia. RESULTS A total of 11 clinical trials were considered eligible for the meta-analysis. The relative risks of all-grade anemia, leucopenia, neutropenia, febrile neutropenia and thrombocytopenia were 0.88 (95% CI: 0.80-0.96; p = 0.007), 1.13 (95% CI: 0.85-1.49; p = 0.41), 1.25 (95% CI: 1.08-1.44; p = 0.002), 1.63 (95% CI: 1.30-2.06; p < 0.0001), 1.91 (95% CI: 1.52-2.42; p < 0.00001), respectively. CONCLUSION Our meta-analysis has demonstrated an increased risk of febrile neutropenia, all-grade and high-grade neutropenia and thrombocytopenia with ramucirumab-based treatment compared with control.
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Affiliation(s)
- Omar Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham ElHalawani
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Chang AA, Hong T, Ewe SY, Bahrami B, Broadhead GK. The role of aflibercept in the management of diabetic macular edema. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:4389-96. [PMID: 26273198 PMCID: PMC4532215 DOI: 10.2147/dddt.s62778] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept.
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Affiliation(s)
- Andrew A Chang
- Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia ; Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia ; Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Thomas Hong
- Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia ; Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia
| | - Shaun Y Ewe
- Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia ; Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia
| | - Bobak Bahrami
- Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia ; Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia
| | - Geoffrey K Broadhead
- Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia ; Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia ; Save Sight Institute, University of Sydney, Sydney, NSW, Australia
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Economopoulou P, Kotsakis A, Kapiris I, Kentepozidis N. Cancer therapy and cardiovascular risk: focus on bevacizumab. Cancer Manag Res 2015; 7:133-43. [PMID: 26082660 PMCID: PMC4461138 DOI: 10.2147/cmar.s77400] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Recognition and management of treatment-related cardiovascular toxicity, defined as either an acute cardiac event or a chronic condition, has been tightly integrated into routine cancer care and has become an important component in treatment selection. Several chemotherapeutic agents, such as anthracyclines, are traditionally characterized as cardiotoxic, but cardiovascular adverse events are also associated with commonly used molecular targeted therapies. In the past decade, bevacizumab, a monoclonal humanized antibody against vascular endothelial growth factor, has been introduced in the treatment of a variety of metastatic malignancies. Despite its efficacy, bevacizumab has been associated with significant risk of cardiovascular complications, such as hypertension, cardiac ischemia, and congestive heart failure. This review will focus on the cardiovascular toxicity of bevacizumab, providing the latest evidence on the incidence, clinical spectrum, risk factors, and responsible mechanisms.
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Affiliation(s)
- Panagiota Economopoulou
- Medical Oncology Unit, 2nd Department of Internal Medicine, Attikon University Hospital, Haidari, Athens, Greece
| | - Athanasios Kotsakis
- Department of Medical Oncology, University Hospital of Heraklion, Crete, Greece
| | - Ioannis Kapiris
- 251 Airforce General Hospital, Department of Medical Oncology, Athens, Greece
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Effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema. Eur J Ophthalmol 2015; 25:539-45. [PMID: 25907286 DOI: 10.5301/ejo.5000617] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2015] [Indexed: 11/20/2022]
Abstract
PURPOSE To determine the effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema. METHODS Peak systolic velocity, end-diastolic velocity, resistance, and pulsatility indices of central retinal artery (CRA), nasal posterior ciliary artery (NPCA), temporal posterior ciliary artery (TPCA), and ophthalmic artery (OA) were assessed by color Doppler ultrasonography in injected and uninjected eyes of 37 patients at baseline and at day 1 and day 7 after the injection. RESULTS At day 1 after the injection, peak systolic and end diastolic velocities of the CRA and NPCA in the injected eyes and peak systolic velocity of NPCA in the uninjected eyes decreased significantly (p<0.05, p = 0.025, respectively). Peak systolic and end diastolic velocities were not significantly different in the injected and uninjected eyes at day 7 after the injection (p>0.05). In the injected eyes, there was no significant change in resistance and pulsatility indices (p>0.05), but a decrease in resistance index of NPCA and resistance and pulsatility indices of TPCA occurred in uninjected eyes at day 7 after the injection (p = 0.016, p = 0.023, and p = 0.025, respectively). CONCLUSIONS Intravitreal bevacizumab affects retrobulbar blood flow in injected and uninjected eyes of patients with diabetic macular edema.
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Jee D, Zako M, La TY. Serum D-dimer levels to evaluate the risk for arterial thromboembolism after intravitreal injection of bevacizumab and ranibizumab. J Ocul Pharmacol Ther 2014; 31:32-6. [PMID: 25229129 DOI: 10.1089/jop.2013.0234] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
Abstract
PURPOSE There are concerns about arterial thromboembolic event after intravitreal injection of bevacizumab or ranibizumab. Motivated by the fact that D-dimer was a sensitive biomarker for thromboembolism, we evaluated serum D-dimer levels in patients with age-related macular degeneration (AMD) after intravitreal injection of bevacizumab and ranibizumab. METHODS In this prospective, nonrandomized, uncontrolled study, 122 patients (122 eyes) with AMD were enrolled. Sixty-two eyes received intravitreal injections of bevacizumab and 60 eyes received intravitreal injections of ranibizumab monthly for 3 months. Serum D-dimer levels were measured in patients before intravitreal injection and 1 day, 1 week, 1 month, and 3 months thereafter. RESULTS Serum D-dimer levels were not significantly altered following injection of either bevacizumab or ranibizumab. Subgroup analysis for patients at risk for thromboembolic events revealed that serum D-dimer levels showed no significant change after injection of ranibizumab. However, D-dimer levels significantly increased at 1 day (P=0.041) and 1 week (P=0.022) after injection of bevacizumab. CONCLUSIONS Serum D-dimer levels were not changed after injection with either bevacizumab or ranibizumab. In subgroup analysis, bevacizumab injection in patients at risk of thromboembolism increased serum D-dimer levels.
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Affiliation(s)
- Donghyun Jee
- 1 Department of Ophthalmology and Visual Science, St. Vincent Hospital , Suwon, Republic of Korea
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Peng L, Bu Z, Zhou Y, Ye X, Liu J, Zhao Q. Hemorrhagic events in cancer patients treated with aflibercept: a meta-analysis. Tumour Biol 2014; 35:9419-27. [DOI: 10.1007/s13277-014-2189-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 06/03/2014] [Indexed: 12/27/2022] Open
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Liu S, Kurzrock R. Toxicity of targeted therapy: Implications for response and impact of genetic polymorphisms. Cancer Treat Rev 2014; 40:883-91. [PMID: 24867380 DOI: 10.1016/j.ctrv.2014.05.003] [Citation(s) in RCA: 122] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Revised: 05/06/2014] [Accepted: 05/08/2014] [Indexed: 12/11/2022]
Abstract
Targeted therapies have unique toxicity profiles. Common adverse events include rash, diarrhea, hypertension, hypothyroidism, proteinuria, depigmentation, and hepatotoxicity. Some of these toxicities are caused by on-target, mechanism-associated effects, which can be stratified as to whether or not the targets are relevant to response. Other toxicities are off-target and may be caused by the class of agent, e.g. antibody vs small molecule tyrosine kinase inhibitor, or by immune reactions or toxic metabolites. Both on- and off-target toxicities may be due to higher drug concentrations or altered end-organ sensitivity, which in turn can be a consequence of genetic polymorphisms controlling metabolism or tissue responsiveness. On-target toxicities are important to identify as some correlate with response and, hence, amelioration of these side effects is preferable to dose reduction or stopping drug. Toxicities secondary to relevant target impact may be recognized when distinct types of agents, such as antibodies and small molecule kinase inhibitors, with the same target have a similar side effect. For example, both bevacizumab and vascular endothelial growth factor receptor (VEGFR) kinase inhibitors cause hypertension; both epidermal growth factor receptor (EGFR) antibodies and kinase inhibitors cause rash; and these toxicities correlate with response. Herein we review common targeted agent-related toxicities, relevant genetic polymorphisms, and implications for response and patient management.
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Affiliation(s)
- Sariah Liu
- Division of Hematology and Oncology and Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, United States.
| | - Razelle Kurzrock
- Division of Hematology and Oncology and Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, United States
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Ikeda S, Sekine A, Kato T, Yoshida M, Ogata R, Baba T, Nagahama K, Okudela K, Ogura T. Diffuse alveolar hemorrhage as a fatal adverse effect of bevacizumab: an autopsy case. Jpn J Clin Oncol 2014; 44:497-500. [PMID: 24683198 DOI: 10.1093/jjco/hyu023] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
A 71-year-old female with Stage IIIB primary adenocarcinoma was administered a three-drug combination therapy consisting of docetaxel, cisplatin and bevacizumab as a first-line treatment based on the Phase II clinical trial. On the 32nd day after the fourth course of chemotherapy, the patient developed bloody sputum. She was found dead at home on the 34th day. Autopsy revealed a diffuse alveolar hemorrhage without diffuse alveolar damage. Endothelial cells of the small arteries and capillaries were swollen and desquamated, indicating that alveolar capillaries were injured. The similar pathological changes in blood vessels were also observed in the kidney and the digestive tract. Because diffuse alveolar hemorrhage caused by cisplatin and docetaxel has never been reported apart from interstitial pneumonitis, bevacizumab is the most suspicious drug for diffuse alveolar hemorrhage in our case. Chest physicians and oncologists should be aware that although it is very rare, diffuse alveolar hemorrhage can develop during any course of chemotherapy with bevacizumab.
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Affiliation(s)
- Satoshi Ikeda
- *Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Tomioka-Higashi 6-16-1, Kanazawa-ku, Yokohama, Japan.
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Soffietti R, Trevisan E, Rudà R. Neurologic complications of chemotherapy and other newer and experimental approaches. HANDBOOK OF CLINICAL NEUROLOGY 2014; 121:1199-218. [PMID: 24365412 DOI: 10.1016/b978-0-7020-4088-7.00080-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Neurologic complications of conventional cytototxic agents as well as those from monoclonal antibodies and targeted therapies are increasingly observed in patients with cancer. The major categories are represented by alkylating agents (platinum compounds, ifosfamide, procarbazine, thiotepa), mitotic spindle inhibitors (vinca alkaloids, taxanes, etoposide, teniposide), proteasome inhibitors (bortezomib), antibiotics, antimetabolites, thalidomide, lenalidomide, topoisomerase inhibitors, interferon-α, hormones, bevacizumab, trastuzumab, and small tyrosine kinase inhibitors. Peripheral neuropathy is a common adverse effect of a number of chemotherapeutic drugs and often represents a critical factor limiting an adequate dose-intensity of chemotherapy. Regarding the central nervous system (CNS), it is vulnerable to many forms of toxicity from chemotherapeutic agents, including encephalopathy syndromes and confusional states, seizures, headache, cerebrovascular complications, visual loss, cerebellar syndromes, and myelopathy. For a given drug, the occurrence of CNS toxicity depends on several factors, including the total dose, route of administration, presence of structural brain lesions, exposure to prior or concurrent irradiation, and interactions with other drugs. However, many of the neurotoxic reactions are rare and idiosyncratic, and remain unpredictable. Several forms of neuroprotection and rehabilitation are being investigated. Last, the so-called "chemobrain" is an emerging issue, as it is a model of a subtle of and long-lasting damage to neuronal structures from some antineoplastic agents.
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Affiliation(s)
- Riccardo Soffietti
- Division of Neuro-Oncology, Department of Neuroscience, University and San Giovanni Battista Hospital, Turin, Italy.
| | - Elisa Trevisan
- Division of Neuro-Oncology, Department of Neuroscience, University and San Giovanni Battista Hospital, Turin, Italy
| | - Roberta Rudà
- Division of Neuro-Oncology, Department of Neuroscience, University and San Giovanni Battista Hospital, Turin, Italy
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