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1
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Luo J, Du Q, Liu J. Detrimental impact of gastric acid suppressants on vascular endothelial growth factor receptor tyrosine kinase inhibitors efficacy: evidence from a systematic review and meta-analysis. Expert Rev Clin Pharmacol 2025:1-16. [PMID: 40243001 DOI: 10.1080/17512433.2025.2492062] [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: 12/06/2024] [Revised: 03/15/2025] [Accepted: 04/08/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND This meta-analysis evaluated the prevalence of gastric acid suppressants (GASs) in patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and explored drug-drug interactions (DDIs). METHODS PubMed, Embase, and Cochrane Library were searched upto 20 October 2024. Studies comparing VEGFR-TKIs monotherapy versus VEGFR-TKIs with GASs, reporting pharmacodynamic (PD), pharmacokinetic (PK), or adverse events (AEs), were analyzed using random-effects models. Subgroups included cancer types and VEGFR-TKI types. RESULTS 24 studies comprising 6,406 patients were included. The prevalence of GASs use in VEGFR-TKIs users was 40% (95% CI 31-50%). GASs significantly impaired survival, increasing mortality risk by 29% (OS HR 1.29,95% CI 1.14-1.45) and progression risk by 31% (PFS HR 1.31, 95% CI 1.06-1.61). PK analyses revealed clinically meaningful exposure reductions (AUC0-24GMR 0.78, 90% CI 0.65-0.94; Cmax GMR 0.80, 90% CI 0.70-0.91). AE incidence (except vomiting) did not differ between groups. CONCLUSION GASs may reduce the efficacy of most types of VEGFR-TKIs by decreasing their bioavailability, thereby having a detrimental effect on patient survival outcomes. It is recommended to give priority to H2 receptor antagonists (H2RAs) and monitor blood drug concentrations to optimize efficacy. PROTOCOL REGISTRATION www.crd.york.ac.uk/prospero identifier CRD42024597729.
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Affiliation(s)
- Jiefeng Luo
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qiong Du
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiyong Liu
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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2
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Hino U, Tamura R, Toda M. Optimal Delivery of Pain Management in Schwannomatosis: A Literature Review. Ther Clin Risk Manag 2025; 21:61-68. [PMID: 39839825 PMCID: PMC11748755 DOI: 10.2147/tcrm.s362794] [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: 08/29/2024] [Accepted: 01/04/2025] [Indexed: 01/23/2025] Open
Abstract
Non-NF2 schwannomatosis is a rare syndrome characterized by multiple benign schwannomas that primarily affect nerve sheaths, with chronic, treatment-resistant pain as the most common symptom. No protocol has been established for pain management, and pharmacotherapies, including molecular target therapies, are being evaluated. Neuromodulation therapies such as scrambler therapy and surgical options are also employed; however, surgery may lead to persistent or recurrent pain caused by nerve damage or tumor recurrence. The lack of accurate animal models hampers understanding of pain mechanisms and tumor development, necessitating further basic research and clinical trials to improve treatment strategies.
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Affiliation(s)
- Utaro Hino
- Department of Neurosurgery, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan
| | - Ryota Tamura
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Masahiro Toda
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
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3
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Xu M, Li S. Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment. Cancer Lett 2023; 574:216397. [PMID: 37730105 DOI: 10.1016/j.canlet.2023.216397] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/30/2023] [Accepted: 09/11/2023] [Indexed: 09/22/2023]
Abstract
Melanoma, the most aggressive form of cutaneous malignancy arising from melanocytes, is frequently characterized by metastasis. Despite considerable progress in melanoma therapies, patients with advanced-stage disease often have a poor prognosis due to the limited efficacy, off-target effects, and toxicity associated with conventional drugs. Nanotechnology has emerged as a promising approach to address these challenges with nanoparticles capable of delivering therapeutic agents specifically to the tumor microenvironment (TME). However, the clinical approval of nanomedicines for melanoma treatment remains limited, necessitating further research to develop nanoparticles with improved biocompatibility and precise targeting capabilities. This comprehensive review provides an overview of the current research on nano-drug delivery systems for melanoma treatment, focusing on liposomes, polymeric nanoparticles, and inorganic nanoparticles. It discusses the potential of these nanoparticles for targeted drug delivery, as well as their ability to enhance the efficacy of conventional drugs while minimizing toxicity. Furthermore, this review emphasizes the significance of interdisciplinary collaboration between researchers from various fields to advance the development of nanomedicines. Overall, this review serves as a valuable resource for researchers and clinicians interested in the potential of nano-drug delivery systems for melanoma treatment and offers insights into future directions for research in this field.
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Affiliation(s)
- Mengdan Xu
- Department of Hematology and Breast Cancer, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China
| | - Shenglong Li
- Second Ward of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China; The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, China.
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4
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Novak I, Bass LM. Gastrointestinal Bleeding in Children: Current Management, Controversies, and Advances. Gastrointest Endosc Clin N Am 2023; 33:401-421. [PMID: 36948753 DOI: 10.1016/j.giec.2022.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2023]
Abstract
Upper gastrointestinal bleeding (UGIB) in children has many causes, with its prevalence varying by age. Often presenting as hematemesis or melena, the initial treatment is stabilization of the patient, including protection of the airway, fluid resuscitation, and a transfusion hemoglobin threshold of 7 g/L. Endoscopy should be performed with the goal of using combinations of therapies to treat a bleeding lesion, generally involving epinephrine injection along with either cautery, hemoclips, or hemospray. This review discusses the diagnosis and treatment of variceal and non-variceal gastrointestinal bleeding in children with a focus on current advances in the treatment of severe UGIB.
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Affiliation(s)
- Inna Novak
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY 10467, USA.
| | - Lee M Bass
- Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E Chicago Avenue, Chicago, IL 60611, USA
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5
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Li XQ, Zhu KW, Lai J, Wu J, Guo XF. Esophageal Ulcer After Intravitreal Ranibizumab Injection in a Patient With Age-Related Macular Degeneration. Gastroenterology Res 2023; 16:118-124. [PMID: 37187551 PMCID: PMC10181341 DOI: 10.14740/gr1603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 03/16/2023] [Indexed: 05/17/2023] Open
Abstract
Ranibizumab is a monoclonal antibody fragment targeted against vascular endothelial growth factor (VEGF) A isoform (VEGF-A). This study aimed to report a case of esophageal ulcer that developed soon after intravitreal ranibizumab injection in a patient with age-related macular degeneration (AMD). A 53-year-old male patient diagnosed with AMD received ranibizumab through intravitreal injection in the left eye. Mild dysphagia occurred 3 days after receiving intravitreal ranibizumab injection for the second time. The dysphagia exacerbated remarkably and was accompanied by hemoptysis 1 day after receiving ranibizumab for the third time. Severe dysphagia accompanied by intense retrosternal pain and pant emerged after injecting ranibizumab for the fourth time. An esophageal ulcer was observed through ultrasound gastroscopy, covered with fibrinous tissue, and surrounded by flushing and congestive mucosae. The patient received proton pump inhibitor (PPI) therapy combined with traditional Chinese medicine (TCM) after discontinuation of ranibizumab. The dysphagia and retrosternal pain were gradually relieved after treatment. Afterwards, the esophageal ulcer has not relapsed since permanent discontinuation of ranibizumab. To our best knowledge, this was the first case of esophageal ulcer related to intravitreal ranibizumab injection. Our study indicated that VEGF-A played a potential role in the development of esophageal ulceration.
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Affiliation(s)
- Xin Qing Li
- Department of Pharmacy, Ganzhou People’s hospital (The Affiliated Ganzhou Hospital of Nanchang University), Ganzhou 341000, Jiangxi Province, China
- These authors have contributed equally to this article
- Corresponding Author: Xin Qing Li, Department of Pharmacy, Ganzhou People’s hospital (The Affiliated Ganzhou Hospital of Nanchang University), Ganzhou 341000, Jiangxi Province, China.
| | - Ke Wei Zhu
- Office of Pharmacovigilance, Guangzhou Baiyunshan Pharmaceutical Holding Co., Ltd. Baiyunshan Pharmaceutical General Factory, Guangzhou 510515, Guangdong Province, China
- These authors have contributed equally to this article
| | - Jun Lai
- Department of Pharmacy, Ganzhou People’s hospital (The Affiliated Ganzhou Hospital of Nanchang University), Ganzhou 341000, Jiangxi Province, China
| | - Jian Wu
- Department of Pharmacy, Ganzhou People’s hospital (The Affiliated Ganzhou Hospital of Nanchang University), Ganzhou 341000, Jiangxi Province, China
| | - Xiao Fang Guo
- Department of Gastroenterology, Ganzhou People’s hospital (The Affiliated Ganzhou Hospital of Nanchang University), Ganzhou 341000, Jiangxi Province, China
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6
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The possibility of angiogenesis inhibition in cutaneous melanoma by bevacizumab-loaded lipid-chitosan nanoparticles. Drug Deliv Transl Res 2023; 13:568-579. [PMID: 36058987 DOI: 10.1007/s13346-022-01215-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2022] [Indexed: 12/30/2022]
Abstract
Cutaneous malignant melanoma is fastest-growing cancer in white populations with a large majority of dermal cancer death. The activity of vascular endothelial growth factors (VEGFs) results in the signaling of a variety of downstream intracellular pathways that ultimately leads to cell activation, proliferation, migration, and angiogenesis. VEGF inhibitors such as bevacizumab are widely used in chemotherapy with systemic administration, which in many cases is associated with a variety of side effects. Here, we designed and synthesized a lipid-polymer nanoparticle for local administration of bevacizumab. Drug release, dermal absorption, and the effects of synthesized nanoparticles containing bevacizumab on cell proliferation and in vitro and in vivo angiogenesis were investigated. Encapsulating bevacizumab in the synthesized nanoparticles resulted in a significant increase in its dermal absorption compared to free bevacizumab. Also, the suppressor effects of bevacizumab encapsulated in the synthesized nanoparticle on cell proliferation and angiogenesis were significantly more than those of free bevacizumab. Our findings indicate the remarkable effects of lipid-polymer nanoparticles in dermal absorption and in maintaining bevacizumab bioactivity, suggesting therapeutic benefits of local bevacizumab administration for angiogenesis-related disorders such as cutaneous melanoma. Chitosan nanoparticles containing bevacizumab antibody were synthesized by ion exchange method, and finally, these nanoparticles were coated with lipid (Lip-Chi-Bev NPs). In this study, the effect of synthesized nanoparticles on dermal absorption of bevacizumab was evaluated and its potential in inhibiting angiogenesis was evaluated by in vitro and in vivo models.
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7
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Zhang P, Mao R, Zhang C, Qiu Y, Chen M. Gastrointestinal injury induced by immunomodulators: A review article. Therap Adv Gastroenterol 2023; 16:17562848231158549. [PMID: 37113189 PMCID: PMC10126616 DOI: 10.1177/17562848231158549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 02/02/2023] [Indexed: 04/29/2023] Open
Abstract
An increasing number of immunomodulators, either anti-inflammatory or immunity-enhancing, have brought about a revolutionary effect in the management of a variety of autoimmune disorders and malignancies. However, their ability to cause gastrointestinal (GI) injury and induce GI symptoms has been increasingly and unexpectedly recognized. GI injury associated with immunomodulators may demonstrate various histologic and endoscopic patterns. Optimal diagnosis and treatment require a multidisciplinary approach. This review aims to provide an overview of the literature on its pathogenesis, the clinical, endoscopic, and histologic features, and suggested approaches to manage these newly recognized immunomodulator-induced GI adverse effects (AEs). We also reviewed current biomarkers predictive of GI toxicity and potential risk factors to identify susceptible patients. In addition, these immune-mediated AEs were compared with inflammatory bowel disease, a well-documented form of inflammation-driven GI injury. We hope this review will raise awareness and vigilance among clinicians of these entities to increase early diagnosis and rapid referral to specialist care.
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Affiliation(s)
- Pingxin Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Ren Mao
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | - Chuhan Zhang
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
| | | | - Minhu Chen
- Department of Gastroenterology, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province,
China
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8
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Tracheoesophageal Fistula and Esophageal Perforation in a Patient with Advanced Gastroesophageal Junction Tumor Post Ramucirumab Treatment. A case report and literature review. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2022. [DOI: 10.1016/j.cpccr.2022.100214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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9
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Erol C, Sendur MAN, Yalçin B. An unusual infection with long-term bevacizumab treatment for advanced nonsmall-cell lung cancer: Actinomycosis. J Cancer Res Ther 2022; 18:1809-1810. [PMID: 36412450 DOI: 10.4103/jcrt.jcrt_2083_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Bevacizumab is an angiogenesis inhibitor with Food and Drug Administration approval for multiple tumor types (including colon, nonsquamous nonsmall-cell lung cancer, kidney and glioblastoma multiforme, cervix, and ovarian cancer). Here, we present a patient with actinomycosis who was on treatment with bevacizumab maintenance therapy following chemotherapy combined with bevacizumab. A 60-year-old male patient with lung adenocarcinoma was treated four cycles of carboplatin, paclitaxel with bevacizumab. And then, bevacizumab maintenance therapy was continued. After 38 months of bevacizumab maintenance, computed tomography showed a newly developed cavitary lesion in the upper lobe of the right lung. Bronchoscopy was performed and the pathology report of the biopsy was reported as actinomycosis. Bevacizumab treatment was discontinued and the patient was treated with amoxicillin-clavulanate. To our knowledge, our case is the first case of actinomycosis infection due to the possible bevacizumab treatment.
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Affiliation(s)
- Cihan Erol
- Department of Medical Oncology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Mehmet Ali Nahit Sendur
- Department of Medical Oncology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Bülent Yalçin
- Department of Medical Oncology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey
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10
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Azam M, Hudgi A, Uy PP, Makhija J, Yap JEL. Safety of endoscopy in patients undergoing treatments with antiangiogenic agents: A 5-year retrospective review. World J Gastrointest Endosc 2022; 14:416-423. [PMID: 36051996 PMCID: PMC9329849 DOI: 10.4253/wjge.v14.i7.416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/08/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Antiangiogenic agents (AAs) are increasingly used to treat malignant tumors and have been associated with gastrointestinal (GI) bleeding and perforation. Elective surgeries and endoscopy are recommended to be delayed for 31 d until after AAs treatment. Data regarding the safety of endoscopy while on antiangiogenic agents is extremely limited. No guidelines are in place to address the concern about withholding these anti-angiogenic drugs.
AIM To evaluate the risks of endoscopy in patients on antiangiogenic agents from 2015 to 2020 at our institution.
METHODS This is a single centered retrospective study approved by the institutional review board statement of the institution. Patients that underwent endoscopy within 28 d of antiangiogenic agents’ treatment were included in the study. Primary outcome of interest was death, and secondary outcomes included perforation and GI bleeding. Data were analyzed utilizing descriptive statistics. Fifty-nine patients were included in the final analysis and a total of eighty-five procedures were performed that were characterized as low risk and high risk.
RESULTS Among the 59 patients a total of 85 endoscopic procedures were performed with 24 (28.2%) categorized as high-risk and 61 (71.8%) procedures as low-risk. Of the total number of patients, (50%) were on bevacizumab and the rest were on imatinib (11.7%), lenvatinib (6.7%) and, ramucirumab (5%). The average duration between administration of AAs and the performance of endoscopic procedures was 9.9 d. No procedure-related adverse events were noted among our study population. We did observe two deaths with one patient, on lenvatinib for metastatic hepatocellular carcinoma, who had persistent bleeding despite esophageal variceal banding and died 4 d later from hemorrhagic shock. Another patient was diagnosed with acute myeloid leukemia died 24 d after an esophagogastroduodenoscopy with biopsy after transition to comfort care.
CONCLUSION As per this single center retrospective study, the rate of endoscopic procedure-related adverse events and death within 28 d of AA administration appears to be low.
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Affiliation(s)
- Mohammad Azam
- Department of Internal Medicine, Medical College of Georgia/Augusta University, Augusta, GA 30912, United States
| | - Amit Hudgi
- Department of Internal Medicine, Medical College of Georgia/Augusta University, Augusta, GA 30912, United States
| | - Pearl Princess Uy
- Division of Gastroenterology, Medical College of Georgia/Augusta University, Augusta, GA 30912, United States
| | - Jinal Makhija
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, United States
| | - John Erikson L Yap
- Division of Gastroenterology, Medical College of Georgia/Augusta University, Augusta, GA 30912, United States
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11
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Brown AD, Traynor MD, Potter DD, Ishitani MB, Moir CR, Galardy PJ, Klinkner DB. Evolution of pediatric gastrointestinal ulcer disease: Is acute surgical intervention relevant? J Pediatr Surg 2021; 56:1870-1875. [PMID: 33678404 DOI: 10.1016/j.jpedsurg.2021.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND There is a lack of contemporary data about pediatric gastrointestinal ulcer disease. We hypothesized that ulcers found in immunosuppressed children were more likely to require surgical intervention. METHODS All children <21 years (n = 129) diagnosed with ulcers at a quaternary hospital from 1990 to 2019 were retrospectively reviewed. Clinical findings and pertinent information were collected. RESULTS Of 129 cases, 19 (14.7%) were immunosuppressed. Eight were post-transplant; four were diagnosed with post-transplant lymphoproliferative disease (PTLD). Eight were associated with cancer. Three were both. Three of 19 immunosuppressed and 28/110 immunocompetent patients were taking acid suppression therapy. Nine immunosuppressed patients required surgical intervention, including all PTLD cases, compared to 14 immunocompetent (47.3% vs 16.4%, p < 0.01). Five patients had duodenal perforation, two had multiple small bowel perforations, and two had uncontrolled bleeding. Of 9/19 immunosuppressed patients, surgical complications included bleeding (n = 7), sepsis (n = 2), ostomy reoperation/readmissions (n = 2), and death within 30 days (n = 2). Two/eighteen immunocompetent patients had bleeding complications. CONCLUSION Surgical treatment for ulcers remains relevant for pediatric patients. Immunosuppressed patients have more complications, longer hospital stays, and are more likely to need surgical intervention. Efforts should be made for ulcer prophylaxis with a low threshold to investigate epigastric pain in these complex patients. LEVEL OF EVIDENCE Prognosis Study Level III Evidence.
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Affiliation(s)
- Alyssa D Brown
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA
| | - Michael D Traynor
- Department of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
| | - D Dean Potter
- Department of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA; Division of Pediatric Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
| | - Michael B Ishitani
- Department of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA; Division of Pediatric Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
| | - Christopher R Moir
- Department of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA; Division of Pediatric Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
| | - Paul J Galardy
- Division of Pediatric Hematology and Oncology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
| | - Denise B Klinkner
- Department of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA; Division of Pediatric Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
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Suoh M, Hagihara A, Yamamura M, Maruyama H, Taira K, Enomoto M, Tamori A, Fujiwara Y, Kawada N. Obstructive Jaundice Due to Duodenal Ulcer Induced by Lenvatinib Therapy for Hepatocellular Carcinoma. Intern Med 2021; 60:545-552. [PMID: 33028766 PMCID: PMC7946507 DOI: 10.2169/internalmedicine.5097-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 08/07/2020] [Indexed: 12/19/2022] Open
Abstract
An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.
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Affiliation(s)
- Maito Suoh
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan
| | - Masafumi Yamamura
- Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Hirotsugu Maruyama
- Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Koichi Taira
- Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Japan
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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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Intestinal Perforation due to Neutropenic Enterocolitis in a Patient Treated with Bevacizumab for Ovarian Cancer. Case Rep Oncol Med 2020; 2020:7231358. [PMID: 32612862 PMCID: PMC7317333 DOI: 10.1155/2020/7231358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 05/28/2020] [Accepted: 06/02/2020] [Indexed: 01/03/2023] Open
Abstract
Intestinal perforation is a rare adverse event of antineoplastic therapy. However, once it occurs, it is potentially fatal. This report describes a case of intestinal perforation caused by bevacizumab in a patient with ovarian cancer who concurrently developed neutropenic enterocolitis. A 66-year-old woman diagnosed with metastatic ovarian cancer received combination chemotherapy with carboplatin, gemcitabine, and bevacizumab. On day 14, she developed grade 4 pancytopenia and febrile neutropenia, which resulted in neutropenic enterocolitis and intestinal perforation. Emergency surgery was performed, and an intestinal perforation found in the ascending colon was closed. Postoperatively, she developed an intra-abdominal abscess requiring peritoneal drainage. She was discharged from the hospital on recovery.
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Korkmaz L, Coşkun HŞ, Dane F, Karabulut B, Karaağaç M, Çabuk D, Karabulut S, Aykan NF, Doruk H, Avcı N, Turhal NS, Artaç M. Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study. Surg Oncol 2018; 27:485-489. [PMID: 30217306 DOI: 10.1016/j.suronc.2018.05.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 02/05/2023]
Abstract
PURPOSE We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC). METHODS We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens. RESULTS The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients. CONCLUSION Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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Affiliation(s)
- Levent Korkmaz
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Hasan Şenol Coşkun
- Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Bülent Karabulut
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Mustafa Karaağaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Devrim Çabuk
- Department of Medical Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Nuri Faruk Aykan
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Hatice Doruk
- Department of Medical Oncology, Acıbadem Bursa Hospital, Bursa, Turkey
| | - Nilüfer Avcı
- Department of Medical Oncology, Ali Osman Sönmez Oncology Hospital, Bursa, Turkey
| | | | - Mehmet Artaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey.
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So HM, Eom HJ, Lee D, Kim S, Kang KS, Lee IK, Baek KH, Park JY, Kim KH. Bioactivity evaluations of betulin identified from the bark of Betula platyphylla var. japonica for cancer therapy. Arch Pharm Res 2018; 41:815-822. [DOI: 10.1007/s12272-018-1064-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Accepted: 08/01/2018] [Indexed: 01/25/2023]
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Abstract
The antivascular endothelial growth factor antibody, bevacizumab, is effective against several malignancies in adults but unproven in pediatric oncology. In early phase pediatric studies toxicities were similar to those in adults. Bowel perforation in adults is a rare but serious toxicity, but has not been hitherto reported in children. A 5-year-old boy with chemoresistant neuroblastoma treated with bevacizumab plus radioimmunotherapy developed acute abdominal pain. Computed tomography scan showed free abdominal air and pneumatosis coli. Emergency laparotomy and bowel diversion were performed leading to complete recovery and timely continuation of antineuroblastoma therapy. Early recognition and rapid intervention can prevent a catastrophic outcome in bevacizumab-related bowel perforation.
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Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer. Invest New Drugs 2018. [PMID: 29536229 DOI: 10.1007/s10637-018-0581-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37-51.63, p = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37-54.50, p = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98-42.49, p = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01-21.04, p = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.
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Current insight into pathophysiology of gastroduodenal ulcers: Why do only some ulcers perforate? J Trauma Acute Care Surg 2018; 80:1045-8. [PMID: 26998777 DOI: 10.1097/ta.0000000000001035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Park SG, Chung CH, Park CY. Colon Perforation during Sorafenib Therapy for Advanced Hepatocelluar Carcinoma. A Case Report. TUMORI JOURNAL 2018; 97:794-9. [DOI: 10.1177/030089161109700618] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile. Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.
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Affiliation(s)
- Sang-Gon Park
- Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju, Korea
| | - Choon-Hae Chung
- Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju, Korea
| | - Chi-Young Park
- Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju, Korea
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Kachaamy T, Gupta D, Edwin P, Vashi P. Safety of endoscopy in cancer patients on antiangiogenic agents: A retrospective multicenter outcomes study. PLoS One 2017; 12:e0176899. [PMID: 28472195 PMCID: PMC5417598 DOI: 10.1371/journal.pone.0176899] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 03/11/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS The use of antiangiogenic agents (AAs) in cancer treatment has increased because they offer survival benefit in combination with cytotoxic chemotherapy. Given their potential to cause gastrointestinal (GI) perforation and bleeding, it is currently recommended that AAs be held for 28 days before and after surgery. However, there are no specific guidelines which address their use around endoscopic procedures because data regarding the safety of endoscopy in cancer patients while on AAs is scarce despite the fact that these patients often require endoscopy. This study investigated the safety of endoscopy in cancer patients receiving AAs. METHODS This is a retrospective multicenter study of a consecutive case series of 445 cancer patients undergoing endoscopy within 31 days of administration of AAs at 5 specialized cancer centers between April 2008 and August 2014. Endoscopies were classified into two different categories based on the risk of GI bleeding and perforation: low and high. The primary outcome measures were procedure-related adverse events (AEs) and death within 30 days of endoscopy. The severity of AEs was classified according to the common terminology criteria for adverse events (CTCAE) version 4.0. The incidence of AEs and mortality was calculated using the total number of patients as the denominator. RESULTS 445 cancer patients with a mean age of 54 years underwent a total of 545 endoscopies. Median time duration from AAs to endoscopy was 11 days. Of 545 endoscopic procedures, 398 (73%) were low-risk and 147 (27%) were high-risk. There were 3 procedure-related AEs: esophageal perforation (grade 3) two days after an EGD, pancreatitis (grade 5) a day after failed ERCP, and bleeding from the gastrostomy site (grade 1) two days after an EGD. Of 445 patients, 29 (6.5%) died within 30 days of the procedure with no deaths deemed procedure-related. The most common causes of death were terminal cancer (n = 10), hepatic decompensation (n = 5) and sepsis (n = 4). CONCLUSION In this retrospective study, the rate of endoscopy-related AEs in patients on AAs appears to be low when performed in specialized cancer centers. However, future prospective studies are needed to confirm this finding.
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Affiliation(s)
- Toufic Kachaamy
- Cancer Treatment Centers of America, 5900 Broken Sound Parkway, Boca Raton, Florida, United States of America
| | - Digant Gupta
- Cancer Treatment Centers of America, 5900 Broken Sound Parkway, Boca Raton, Florida, United States of America
| | - Persis Edwin
- Cancer Treatment Centers of America, 5900 Broken Sound Parkway, Boca Raton, Florida, United States of America
| | - Pankaj Vashi
- Cancer Treatment Centers of America, 5900 Broken Sound Parkway, Boca Raton, Florida, United States of America
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Scarpignato C, Gatta L, Zullo A, Blandizzi C. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med 2016; 14:179. [PMID: 27825371 PMCID: PMC5101793 DOI: 10.1186/s12916-016-0718-z] [Citation(s) in RCA: 274] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 10/14/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .
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Affiliation(s)
- Carmelo Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy.
| | - Luigi Gatta
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy
- Gastroenterology & Endoscopy Unit, Versilia Hospital, Azienda USL Toscana Nord Ovest, Lido di Camaiore, Italy
| | - Angelo Zullo
- Division of Gastroenterology & Digestive Endoscopy, Nuovo Regina Elena Hospital, Rome, Italy
| | - Corrado Blandizzi
- Division of Pharmacology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
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Wang Z, Zhang J, Zhang L, Liu P, Xie Y, Zhou Q. Risk of gastrointestinal perforation in cancer patients receiving ramucirumab: a meta-analysis of randomized controlled trials. J Chemother 2016; 28:328-34. [PMID: 26099278 DOI: 10.1179/1973947815y.0000000053] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE Although existing evidence from clinical trials has demonstrated manifestation of gastrointestinal perforation with the use of ramucirumab, overall risks have yet to be reported. Therefore, we performed a meta-analysis of published randomized controlled trials (RCTs) to get a better understanding of the overall incidence and risk of gastrointestinal perforation associated with ramucirumab. METHODS The PubMed and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant studies published up to 01 May 2015. Eligible studies included randomized trials of ramucirumab either alone or in combination with another agent compared with the control arm without ramucirumab and that reported gastrointestinal perforation event. Overall incidence, relative risk (RR) and 95% confidence intervals (CI) were computed using fixed- or random-effects models depending on the heterogeneity of the included studies. RESULTS A total of 4579 patients with a variety of solid malignancies from six RCTs were included in our meta-analysis. The incidence of gastrointestinal perforation related to ramucirumab was 1.5% (95% CI 1.1-2.1%) with a mortality of 29.8% (95% CI 14.9-50.7%). The RR of gastrointestinal perforation associated with ramucirumab was 2.56 (95% CI 1.29-5.09; P = 0.007). CONCLUSIONS Treatment with the ramucirumab is associated with a significant increase in risk of gastrointestinal perforation in cancer patients.
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Affiliation(s)
- Zexing Wang
- a Department of Oncology , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
| | - Jun Zhang
- a Department of Oncology , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
| | - Liang Zhang
- b Department of Urology and Institute of Prostatic Diseases , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
| | - Pengying Liu
- a Department of Oncology , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
| | - Yamin Xie
- a Department of Oncology , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
| | - Qin Zhou
- a Department of Oncology , Wuhu No. 2 People's Hospital Affiliated to Wannan Medical College , Anhui Province , China
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Abdel-Rahman O, ElHalawani H. Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with ramucirumab: a systematic review and meta-analysis. Expert Opin Drug Saf 2015; 14:1495-506. [PMID: 26313327 DOI: 10.1517/14740338.2015.1074677] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab. PATIENTS AND METHODS Eligible studies included randomized Phase II and III trials of patients with solid tumors on ramucirumab: describing events of stomatitis, diarrhea, GI perforation and GI hemorrhage. RESULTS Our search strategy yielded 167 potentially relevant citations from Pubmed/Medline, CENTRAL Cochrane registry, European society of medical oncology meeting abstracts and American Society of Clinical Oncology meeting library. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The RR of all-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 1.62 (95% CI 1.31 - 2.00; p < 0.00001), 1.15 (95% CI 1.07 - 1.24; p < 0.0001), 3.29 (95% CI 1.54 - 7.04; p = 0.002) and 1.92 (95% CI 1.03 - 3.57; p = 0.04), respectively. The RR of high-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 2.72 (95% CI 1.76 - 4.19; p < 0.00001), 1.28 (95% CI 0.96 - 1.71; p = 0.09), 3.37 (95% CI 1.51 - 7.54; p = 0.03) and 1.26 (95% CI 0.79 - 2.01; p = 0.34), respectively. CONCLUSIONS Our meta-analysis has demonstrated that ramucirumab-based combination treatment is associated with an increased risk of high-grade stomatitis and GI perforation compared to control treatment.
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Affiliation(s)
- Omar Abdel-Rahman
- a Ain Shams University, Clinical Oncology Department, Faculty of Medicine , Lotfy Elsayed Street, Cairo 11665, Egypt +20 33 028 656 ;
| | - Hesham ElHalawani
- a Ain Shams University, Clinical Oncology Department, Faculty of Medicine , Lotfy Elsayed Street, Cairo 11665, Egypt +20 33 028 656 ;
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Bruketa T, Majerovic M, Augustin G. Rectal cancer and Fournier's gangrene - current knowledge and therapeutic options. World J Gastroenterol 2015; 21:9002-9020. [PMID: 26290629 PMCID: PMC4533034 DOI: 10.3748/wjg.v21.i30.9002] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Revised: 05/08/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
Fournier's gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects.
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Shukla PA, Ahuja J, Kurli V, Patel RI, Kozuch PS. Gastric Perforation Following Prophylactic Embolization of Right Gastric and Gastroduodenal Arteries Prior to Selective Internal Radiation Therapy. Cardiovasc Intervent Radiol 2015; 38:1645-8. [PMID: 26071106 DOI: 10.1007/s00270-015-1139-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 05/10/2015] [Indexed: 11/24/2022]
Abstract
Prophylactic gastroduodenal artery (GDA) and right gastric artery (RGA) embolization for prevention of gastric ulceration in patients with hepatic metastases from colorectal cancer undergoing Selective Internal Radiation Therapy (SIRT) are relatively safe. Herein, we present a case of gastric perforation following prophylactic embolization of the GDA and RGA for SIRT in a 43-year-old male with sigmoid colon adenocarcinoma and multiple hepatic metastases.
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Affiliation(s)
- Pratik A Shukla
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Medical Center, First Avenue at Sixteenth Street, New York, 10003, USA.
| | - Jitesh Ahuja
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Medical Center, First Avenue at Sixteenth Street, New York, 10003, USA
| | - Vineel Kurli
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Medical Center, First Avenue at Sixteenth Street, New York, 10003, USA
| | - Rajesh I Patel
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Medical Center, First Avenue at Sixteenth Street, New York, 10003, USA.
| | - Peter S Kozuch
- Division of Medical Oncology, Department of Medicine, Mount Sinai Beth Israel Medical Center, First Avenue at Sixteenth Street, New York, 10010, USA
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Abstract
Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and mortality as compared with other malignancies. Standard treatment for GBM results in survival of 12.9 months (95% CI: 12.3-13.7 months) with a median progression-free survival of 7.2 months (95% CI: 6.4-8.2 months) in a modern GBM cohort. These aggressive tumors recur and treatment for recurrent GBM continues to have very poor outcomes. Prior to the use of bevacizumab, monoclonal antibody to VEGF, 6-month progression-free survival in clinical trials for recurrent GBM ranged from 9 to 15%. Trials utilizing bevacizumab and its subsequent US FDA approval have given more hope to recurrent GBM and this concise review discusses bevacizumab in recurrent GBM. This review focuses on time-to-event outcomes (overall survival, progression-free survival and 6-month progression-free survival) in clinical trials utilizing bevacizumab for the treatment of recurrent GBM. For this review, we have chosen to focus primarily on Phase II clinical trials that have been published and available in the literature (PubMed). While we focused primarily on time-to-event variables, toxicity and safety of bevacizumab is very important and this agent can be associated with serious life-threatening toxicities. We have included a general section of toxicities but for a more lengthy review please see the excellent study by Odia and colleagues.
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Affiliation(s)
- Ashley Ghiaseddin
- The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, PO Box 3624, Durham, NC 27710, USA
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Qi WX, Shen F, Qing Z, Xiao-Mao G. Risk of gastrointestinal perforation in cancer patients treated with aflibercept: a systematic review and meta-analysis. Tumour Biol 2014; 35:10715-22. [PMID: 25070487 DOI: 10.1007/s13277-014-2369-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 07/15/2014] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) perforation is a serious adverse event associated with aflibercept, a novel vascular endothelial growth factor (VEGF)-targeted agent currently approved as second-line treatment for previously treated metastatic colorectal cancer, but the incidence and risk of GI perforation associated with aflibercept has not been well determined. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing GI perforation associated with aflibercept. Databases from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meeting up to January, 2014 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on GI perforation. Statistical analyses were conducted to calculate the summary incidence, odds ratio, and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. A total of 4,101 patients with a variety of solid tumors from eight clinical trials were included in our analysis. The incidence of GI perforation associated with aflibercept was 1.9% (95%CI, 1.0-3.8%), with a mortality of 10.8% (95%CI, 4.1-25.5%). In addition, patients treated with aflibercept had a significantly increased risk of developing all-grade (OR 3.76; 95%CI, 1.94-7.25; p < 0.001) and high-grade GI (OR 4.14; 95%CI; 2.12-8.06; p < 0.001) perforation compared with patients treated with control medication. No evidence of publication bias was observed. The use of aflibercept is associated with a significantly increased risk of GI perforation compared to controls.
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Affiliation(s)
- Wei-Xiang Qi
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China
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Abstract
Tumor-bowel fistula is an under reported complication of abdomino-pelvic malignancies which may occur spontaneously due to tumor growth or can be associated with cancer treatment. Chemotherapy and radiotherapy are commonly responsible for tumor-bowel fistulas. Molecular targeted therapies are a new class of drugs that can cause tumor fistulization due to their antiangiogenic properties. Clinically, the fistula can be asymptomatic or can result in devastating complications. Imaging helps in the prompt detection of these fistulas and the complications associated with them. Management of tumor-bowel fistula is individualized but often involves discontinuation of the associated treatment. Radiologists should promptly alert the oncology team about the presence of tumor-bowel fistula and any risk factors for its occurrence like pneumatosis or large metastatic deposits close to bowel loops.
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Burger RA, Brady MF, Bookman MA, Monk BJ, Walker JL, Homesley HD, Fowler J, Greer BE, Boente M, Fleming GF, Lim PC, Rubin SC, Katsumata N, Liang SX. Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study. J Clin Oncol 2014; 32:1210-7. [PMID: 24637999 PMCID: PMC3986384 DOI: 10.1200/jco.2013.53.6524] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. PATIENTS AND METHODS Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. RESULTS Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). CONCLUSION History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.
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Affiliation(s)
- Robert A. Burger
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Mark F. Brady
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Michael A. Bookman
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Bradley J. Monk
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Joan L. Walker
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Howard D. Homesley
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Jeffrey Fowler
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Benjamin E. Greer
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Matthew Boente
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Gini F. Fleming
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Peter C. Lim
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Stephen C. Rubin
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Noriyuki Katsumata
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
| | - Sharon X. Liang
- Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center–GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY
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Babacan T, Turkbeyler IH, Dag MS, Dilli I, Balakan O, Altundag K. Cetuximab-induced esophageal ulcer: the first report in literature. Libyan J Med 2014; 9:23723. [PMID: 24560381 PMCID: PMC3935468 DOI: 10.3402/ljm.v9.23723] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Taner Babacan
- Department of Oncology, School of Medicine, Hacettepe University, Ankara, Turkey
| | | | - Muhammet Sait Dag
- Department of Gastroenterology, School of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ismail Dilli
- Department of Internal Medicine, School of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ozan Balakan
- Department of Internal Medicine, School of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Kadri Altundag
- Department of Oncology, School of Medicine, Gaziantep University, Gaziantep, Turkey
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Tirumani SH, Shinagare AB, Jagannathan JP, Krajewski KM, Ramaiya NH. Multidetector-row CT of tumour-bowel fistula: Experience at a tertiary cancer centre. Clin Radiol 2013; 69:e100-7. [PMID: 24290835 DOI: 10.1016/j.crad.2013.09.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 09/21/2013] [Accepted: 09/25/2013] [Indexed: 10/26/2022]
Abstract
AIM To study the clinical and multidetector computed tomography (MDCT) features of tumour-bowel fistula (TBF). MATERIALS AND METHODS Fifty-one patients (27 women; mean age 57.4 years, range 30-77years) with TBF presenting to our institution between January 2005 and February 2012 were identified retrospectively from the radiology database. MDCT images before, at, and subsequent to diagnosis of TBF were reviewed by three radiologists in consensus; clinical presentation, management, and outcome were documented from electronic medical records. RESULTS Of 51 patients, small bowel (n = 22) was the most common site with gastrointestinal stromal tumour (GIST) being the most common sarcoma subtype (n = 10). TBF was treatment-associated (TTBF) in 40 patients [78%; 22 of whom had received molecular targeted therapy (MTT)], and spontaneous (STBF) in 11 patients (22%). Thirty-one patients (61%) were symptomatic at the time of TBF detection. TTBF was more often asymptomatic (19/40 versus 1/11; Fisher's exact test p = 0.03). In the TTBF group, 16 had a partial response, seven had stable disease, and 17 had progressive disease. Treatment was discontinued or changed to an alternative regimen in 27/40 patients, and 13/40 patients continued with the same regimen. TBF persisted in 27/33 patients (82%) who underwent CT follow-up. Thirty-one of the 51 patients were deceased at the time of analysis. Time from diagnosis of TBF to death was shorter with STBF (1.8 months) than with TTBF (6.4 months). CONCLUSION TBF is often associated with MTT and can be seen with treatment response or progression. TTBF is more frequently asymptomatic. TBF is usually managed conservatively by discontinuing treatment, but often persists on CT follow-up.
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Affiliation(s)
- S H Tirumani
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - A B Shinagare
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - J P Jagannathan
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - K M Krajewski
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - N H Ramaiya
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Qi WX, Sun YJ, Tang LN, Shen Z, Yao Y. Risk of gastrointestinal perforation in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis. Crit Rev Oncol Hematol 2013; 89:394-403. [PMID: 24182420 DOI: 10.1016/j.critrevonc.2013.10.002] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 08/19/2013] [Accepted: 10/01/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The use of vascular-endothelial growth factor (VEGF) antibody bevacizumab is associated with an increased risk of gastrointestinal (GI) perforation, but the incidence and risk of GI perforation associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has not been well described. We conduct a systematic review and meta-analysis of published trials to evaluate the overall incidence and risk of GI perforation associated with VEGFR-TKIs. METHODS Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to March 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on GI perforation. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS A total of 5352 patients with a variety of solid tumors from 20 clinical trials were included in our analysis. The incidence of GI perforation was 1.3% (95%CI: 0.8-2.0%) among patients receiving VEGFR-TKIs, with a mortality of 28.6% (15.0-47.6%). Patients treated with VEGFR-TKIs did not significantly increase the risk of GI perforation compared with patients treated with control medication, with an OR of 2.99 (95%CI: 0.85-10.53, p=0.089). Sub-group analysis showed that the incidence of GI perforation did not significantly vary with tumor types, VEGFR-TKIs and treatments regimens. No evidence of publication bias was observed. CONCLUSIONS The use of VEGFR-TKIs dose not significantly increase the risk of GI perforation in comparison with the controls. Further studies are recommended to investigate this association and the risk differences among different tumor types, VEGFR-TKIs or treatment regimens.
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Affiliation(s)
- Wei-Xiang Qi
- Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China
| | - Yuan-Jue Sun
- Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China
| | - Li-Na Tang
- Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China
| | - Zan Shen
- Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China
| | - Yang Yao
- Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China.
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Cao Y. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab 2013; 18:478-89. [PMID: 24035587 DOI: 10.1016/j.cmet.2013.08.008] [Citation(s) in RCA: 243] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
White and brown adipose tissues are hypervascularized and the adipose vasculature displays phenotypic and functional plasticity to coordinate with metabolic demands of adipocytes. Blood vessels not only supply nutrients and oxygen to nourish adipocytes, they also serve as a cellular reservoir to provide adipose precursor and stem cells that control adipose tissue mass and function. Multiple signaling molecules modulate the complex interplay between the vascular system and the adipocytes. Understanding fundamental mechanisms by which angiogenesis and vasculatures modulate adipocyte functions may provide new therapeutic options for treatment of obesity and metabolic disorders by targeting the adipose vasculature.
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Affiliation(s)
- Yihai Cao
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden; Department of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
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Barney BM, Markovic SN, Laack NN, Miller RC, Sarkaria JN, Macdonald OK, Bauer HJ, Olivier KR. Increased Bowel Toxicity in Patients Treated With a Vascular Endothelial Growth Factor Inhibitor (VEGFI) After Stereotactic Body Radiation Therapy (SBRT). Int J Radiat Oncol Biol Phys 2013; 87:73-80. [DOI: 10.1016/j.ijrobp.2013.05.012] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2013] [Revised: 05/03/2013] [Accepted: 05/05/2013] [Indexed: 12/18/2022]
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Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci U S A 2013; 110:12018-23. [PMID: 23818623 DOI: 10.1073/pnas.1301331110] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti-VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1-specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF-specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF-specific drugs.
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Fuloria J. Safety profiles of current antiangiogenic therapies for metastatic colorectal cancer. Onco Targets Ther 2012; 5:133-42. [PMID: 22930641 PMCID: PMC3425342 DOI: 10.2147/ott.s31412] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The biological agents approved for the treatment of patients with metastatic colorectal cancer - bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor A, along with cetuximab and panitumumab, two monoclonal antibodies that target the epidermal growth factor receptor - are associated with a number of adverse events that range in severity from relatively mild to potentially life threatening. Hypertension, thromboembolic events, proteinuria, bleeding, and gastrointestinal perforation have all been associated with bevacizumab, while dermatologic toxicities are common with cetuximab and panitumumab. Hypersensitivity reactions and hypomagnesemia are also a concern with cetuximab and panitumumab. The frequency of these adverse events in randomized clinical trials is reviewed, and recommendations for managing these events in patients undergoing treatment for metastatic colorectal cancer are provided.
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Borofsky SE, Levine MS, Rubesin SE, Tanyi JL, Chu CS, Lev-Toaff AS. Bevacizumab-induced perforation of the gastrointestinal tract: clinical and radiographic findings in 11 patients. ACTA ACUST UNITED AC 2012; 38:265-72. [DOI: 10.1007/s00261-012-9913-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Liu P. Campylobacteremia in stage IV gliosarcoma with bevacizumab treatment. J Community Hosp Intern Med Perspect 2012; 2:17217. [PMID: 23882353 PMCID: PMC3714086 DOI: 10.3402/jchimp.v2i1.17217] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2012] [Revised: 02/29/2012] [Accepted: 03/06/2012] [Indexed: 11/17/2022] Open
Abstract
Primary campylobacter enteritis with secondary bacteremia was diagnosed in an immunocompromised patient with stage IV gliosarcoma. She developed mild diarrhea followed by systemic symptoms with transient generalized weakness and fever. She was treated with azithromycin and had a full recovery and without relapse through 2 months of follow-up. Her diagnosis was confirmed by a positive stool culture for Campylobacter sp. and blood culture for Campylobacter jejuni/coli.
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Affiliation(s)
- Ping Liu
- Sun Yat-Sen University of Medical Sciences, Guangzhou, Guangdong, China
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Walraven M, Witteveen PO, Lolkema MPJ, van Hillegersberg R, Voest EE, Verheul HMW. Antiangiogenic tyrosine kinase inhibition related gastrointestinal perforations: a case report and literature review. Angiogenesis 2011; 14:135-41. [PMID: 21188500 PMCID: PMC3102838 DOI: 10.1007/s10456-010-9197-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Accepted: 12/14/2010] [Indexed: 12/11/2022]
Abstract
Anti-VEGF (vascular endothelial growth factor) therapy with the monoclonal antibody bevacizumab can cause gastrointestinal (GI) perforations. In recent years it became apparent that GI perforations also occur during treatment with antiangiogenic tyrosine kinase inhibitors (TKIs). It is of clinical importance to consider (vague) abdominal complaints during antiangiogenic treatment as a sign of a GI perforation. To illustrate this serious complication, we report four cases of antiangiogenic treatment related GI perforations. In three cases this was due to antiangiogenic TKI treatment. Reported risk factors of GI perforations due to bevacizumab include the presence of a primary tumor in situ and recent history of endoscopy or abdominal radiotherapy. Pathology assessments of surgical removal of the perforated intestinal part reveal that perforations are predominantly seen at the tumor or anastomotic site, in case of carcinomatosis or diverticulitis or when GI obstruction or an intra-abdominal abscess is present. Whether the same risk factors may be involved in antiangiogenic TKI related GI perforations is unknown. The underlying mechanisms responsible for GI perforation during antiangiogenic treatment is unknown, but disturbance of host cell homeostasis of immune cells as well as platelet-endothelial cell interactions may play an important role. In conclusion, while clinical awareness that antiangiogenic treatment can cause GI perforations is critical for current medical practice, it is also very important to get more insight in its underlying mechanisms so that this life-threatening complication may be prevented in the near future.
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Affiliation(s)
- Maudy Walraven
- Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Martijn P. J. Lolkema
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - R. van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Emile E. Voest
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - H. M. W. Verheul
- Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Paiva CE, Maia YCDP, Paiva BSR, Lerco MM. Painful cervical esophageal erosion in a patient with advanced colorectal cancer treated with bevacizumab. Invest New Drugs 2010; 28:882-883. [PMID: 19727559 DOI: 10.1007/s10637-009-9312-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2009] [Accepted: 08/20/2009] [Indexed: 12/01/2022]
Affiliation(s)
- Carlos Eduardo Paiva
- Oncological and Hemato-oncological Center, São Paulo State University, Botucatu, SP, Brazil.
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Yang SH, Lin JK, Chen WS, Lin TC, Yang SH, Jiang JK, Chang SC, Lan YT, Chao TC, Yen CC, Tzeng CH, Teng HW. Pneumothorax after bevacizumab-containing chemotherapy: a case report. Jpn J Clin Oncol 2010; 41:269-71. [PMID: 21030401 DOI: 10.1093/jjco/hyq195] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Bevacizumab added to 5-fluorouracil-based chemotherapy can improve outcomes in patients with metastatic colorectal cancer. Bevacizumab had several notable adverse effects including bowel perforation but pneumothorax had never been reported in the available English literature. We reported a 45-year-old male with lung metastases from colorectal cancer who had spontaneous pneumothorax after the second cycle of bevacizumab-containing chemotherapy. His pneumothorax resolved after tube thoracostomy with a small caliber catheter. The mechanism of pneumothorax developed after bevacizumab therapy was not clear as bowel perforation but tumor necrosis with ruptured parietal pleura might be the cause. In patients who had chest discomfort after bevacizumab-containing therapy, pneumothorax should never be overlooked as one of the differential diagnoses.
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Affiliation(s)
- Sheng-Hsiang Yang
- Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan
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Senadhi V, Jani N, Erlich R. Metastatic Renal Cell Cancer and a Gastric Mass: An Unusual Finding. Case Rep Gastroenterol 2010; 4:421-428. [PMID: 21060712 PMCID: PMC2975011 DOI: 10.1159/000320871] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Renal cell cancer (RCC) accounts for approximately 3% of all adult malignancies. RCC has a metastasis rate of approximately 25%, which is most commonly to the lungs (>50%). On the contrary, RCC metastasis to the gastrointestinal tract (excluding the liver) is very uncommon and ranges from 0.2 to 0.7%. Thus, a gastric cancer in a patient with known metastatic RCC would most likely be secondary to metastasis. We present the first reported case of a metastatic RCC coexisting with a new-onset primary gastric cancer and a review of management using guidelines from metastatic RCC to the stomach. An 82-year-old African American male with papillary RCC status post left nephrectomy with recurrence of liver metastasis presented with failure to thrive shortly after his third cycle of chemotherapy despite stable disease by imaging studies. He had received 7 chemotherapy cycles of Gemzar, Nexavar, and Avastin prior to admission. He subsequently had a drop in his hemoglobin and was found to have hemoccult positive stool in the setting of recent Avastin. Endoscopic evaluation showed a 3 cm ulcerated mass in the cardia which was biopsied. The biopsy showed invasive and poorly differentiated gastric adenocarcinoma unrelated to his RCC. The patient subsequently underwent partial gastrectomy with loop gastrojejunostomy for resection of his stage 1 primary gastric adenocarcioma. The surgery also facilitated future chemotherapy (Avastin), which could not be given prior to surgery due to its side effect of bleeding. The patient did not receive adjuvant chemoradiation for his gastric cancer due to his comorbidities at the time and was doing well at a one month follow-up. Metastatic RCC and primary gastric cancer can coexist, especially when there is an overlap of risk factors such as smoking or nitrosamines. The management of a gastric cancer in the setting of metastatic RCC is similar to the management of solitary primary gastric carcinoma. Treatment of the primary gastric cancer can facilitate future chemotherapy such as Avastin, which has been recently approved for the treatment of metastatic RCC.
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Affiliation(s)
- Viplove Senadhi
- Johns Hopkins University/Sinai Hospital Program in Internal Medicine, Department of Internal Medicine, Sinai Hospital, Baltimore, Md., USA
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45
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Tol J, Punt CJA. Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin Ther 2010; 32:437-53. [PMID: 20399983 DOI: 10.1016/j.clinthera.2010.03.012] [Citation(s) in RCA: 135] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2010] [Indexed: 12/23/2022]
Abstract
BACKGROUND Two groups of agents targeting either the vascular endothelial growth factor (VEGF) receptor or the epidermal growth factor receptor (EGFR) have been added to the therapeutic arsenal against metastatic colorectal cancer (mCRC). Currently available agents in these groups are the anti-VEGF antibody bevacizumab and the anti-EGFR antibodies cetuximab and panitumumab. OBJECTIVES This article reviews the results of prospective randomized clinical trials of anti-VEGF and anti-EGFR antibodies in mCRC, either as monotherapy, combined with chemotherapy, or combined with each other. Also reviewed are retrospective subset analyses of the effect of a KRAS mutation on the response to anti-EGFR antibodies. METHODS MEDLINE (2004-2009) was searched for randomized Phase II-III clinical trials of monoclonal antibodies in mCRC published in English. The search terms were colorectal neoplasms, bevacizumab, cetuximab, panitumumab, and KRAS mutation, alone or in combination. Information on the effect of KRAS mutation status on the response to anti-EGFR antibodies was drawn from retrospective subset analyses within the selected trials. RESULTS The literature search identified 5 trials of bevacizumab in mCRC. Of these trials, 3 found a significant benefit on the primary end point (progression-free survival [PFS] or overall survival [OS]) when bevacizumab was added to chemotherapy, either as first-line (2 trials) or second-line (1 trial) treatment. The literature search identified 5 trials of cetuximab and 1 trial of panitumumab in mCRC. Of these trials, 4 found a significant benefit on the primary end point (response rate, PFS, or OS) with cetuximab or panitumumab as monotherapy or added to chemotherapy, either as first-line (1 trial) or later-line (3 trials) treatment. In all trials, the benefit of anti-EGFR therapy was limited to patients who had KRAS wild-type tumors. Of 3 identified trials of combined anti-EGFR and anti-VEGF therapy, 2 found that the combination of an anti-EGFR antibody and the anti-VEGF antibody bevacizumab had a significant negative effect on the primary end point (PFS) compared with no added anti-EGFR antibody. CONCLUSIONS In the studies reviewed, the anti-VEGF antibody bevacizumab added to chemotherapy and the anti-EGFR antibodies cetuximab and panitumumab as monotherapy or added to chemotherapy were associated with consistent efficacy in the treatment of mCRC, although the absolute benefit differed among trials. The efficacy of anti-EGFR antibodies was limited to patients with KRAS wild-type tumors. Given the lack of benefit when anti-VEGF and anti-EGFR antibodies were combined, such regimens should not be used in clinical practice.
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Affiliation(s)
- Jolien Tol
- Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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Current perspective: Bevacizumab in colorectal cancer – A time for reappraisal? Eur J Cancer 2009; 45:2452-61. [DOI: 10.1016/j.ejca.2009.06.028] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Accepted: 06/26/2009] [Indexed: 01/03/2023]
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Hapani S, Chu D, Wu S. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 2009; 10:559-68. [PMID: 19482548 DOI: 10.1016/s1470-2045(09)70112-3] [Citation(s) in RCA: 307] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastrointestinal perforation is a serious adverse event associated with bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF) widely used in current cancer treatment. The association is highlighted by a black-box warning issued by the US Food and Drug Administration, recommending that bevacizumab be permanently discontinued in patients with gastrointestinal perforation. However, no significant association has yet been established between bevacizumab and gastrointestinal perforation in randomised controlled trials. We did a systematic review and meta-analysis of published randomised controlled trials to assess the overall risk of gastrointestinal perforation associated with bevacizumab treatment. METHODS We searched PubMed and Web of Science for articles published between January, 1966, and July, 2008. Additionally, abstracts presented at American Society of Clinical Oncology conferences held between January, 2000, and July, 2008, were searched to identify relevant clinical trials. Eligible studies included prospective randomised controlled trials in which bevacizumab was compared with controls in combination with standard anti-neoplastic therapy. Summary incidence rates, relative risks, and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. FINDINGS 12,294 patients with a variety of solid tumours from 17 randomised controlled trials were included in our analysis. The incidence of gastrointestinal perforation was 0.9% (95% CI 0.7-1.2) among patients receiving bevacizumab, with a mortality of 21.7% (11.5-37.0). Patients treated with bevacizumab had a significantly increased risk of gastrointestinal perforation compared with patients treated with control medication, with a relative risk of 2.14 (95% CI 1.19-3.85; p=0.011). Risk varied with bevacizumab dose and tumour type. Relative risks for patients receiving bevacizumab at 5 and 2.5 mg/kg per week were 2.67 (95% CI 1.14-6.26) and 1.61 (0.76-3.38), respectively. Higher risks were observed in patients with colorectal carcinoma (relative risk 3.10, 95% CI 1.26-7.63) and renal cell cancer (relative risk 5.67, 0.66-48.42). INTERPRETATION The addition of bevacizumab to cancer therapy significantly increased the risk of gastrointestinal perforation compared with controls. The risk may vary with bevacizumab dose and tumour type. Further studies are recommended to investigate the use of bevacizumab in selected patients who have recovered from gastrointestinal perforation. FUNDING Stony Brook University Research Foundation.
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Affiliation(s)
- Sanjaykumar Hapani
- Division of Hematology and Medical Oncology, Department of Medicine, Stony Brook University Medical Center, Stony Brook, NY 11794-9447, USA
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49
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Esophageal ulcer in a patient who received bevacizumab. Invest New Drugs 2009; 28:98-101. [DOI: 10.1007/s10637-009-9246-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2009] [Accepted: 03/19/2009] [Indexed: 01/16/2023]
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