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Yang W, Yang JX, Guan JY, Bao WY, Zhang M. Value of Myocardial Strain in Monitoring Fluorouracil-Based Chemotherapy-Related Cardiac Dysfunction in Gastrointestinal Cancer Patients. CHINESE MEDICAL SCIENCES JOURNAL = CHUNG-KUO I HSUEH K'O HSUEH TSA CHIH 2024; 39:273-281. [PMID: 39789930 DOI: 10.24920/004387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
OBJECTIVES To investigate the predictive value of myocardial strain for cardiotoxicity associated with fluorouracil-based chemotherapies in gastrointestinal cancer patients. METHODS Patients with diagnosis of gastrointestinal cancers, who were hospitalized for chemotherapy involving antimetabolic drugs, were eligible in this prospective study. Echocardiography was performed before and after each chemotherapy cycle during hospitalization until the completion of chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) was identified if there was a decrease in left ventricular ejection fraction (LVEF) by at least 5% to an absolute value of < 53% from the baseline, accompanied by symptoms or signs of heart failure; or a decrease in LVEF of at least 10% to an absolute value of < 53% from the baseline, without symptoms or signs of heart failure. Subclinical cardiac impairment is defined as a decrease in the left ventricular global longitudinal strain (GLS) of at least 15% from baseline.Clinical data and myocardial strain variables were collected. Changes of echocardiographic indexes after chemotherapy at each cycle were observed and compared to those of pre-chemotherapy. Cox regression analysis was used to determine the associated indexes to CTRCD, and receiver operating characteristic (ROC) curves were plotted for evaluation of their predicting efficacy. RESULTS Fifty-one patients completed 4 cycles of chemotherapy and were enrolled in the study analysis. LVEF, GLS, GLS epicardium (GLS-epi), and GLS endocardium (GLS-endo) were decreased after the 4 cycles of chemotherapy. Throughout the chemotherapy period, 6 patients (11.8%) progressed to CTRCD. The Cox regression analysis revealed that the change in left atrial ejection fraction (LAEF) and LAS during the reservoir (LASr) phase after the first cycle of chemotherapy (C1v-LAEF and C1v-LASr, respectively) were significantly associated with the development of CTRCD [C1v-LAEF (HR=1.040; 95%CI: 1.000-1.082; P=0.047); C1v-LASr (HR=1.024; 95%CI: 1.000-1.048; P=0.048)]. The sensitivity and specificity were 50.0% and 93.3%, respectively, for C1v-LAEF predicting CTRCD when C1v-LAEF > 19.68% was used as the cut-off value, and were 66.7% and 75.6%, respectively, for C1v-LASr predicting CTRCD when C1v-LASr > 14.73% was used as the cut-off value. The areas under the ROC curve (AUC) for C1v-LAEF and C1v-LASr predicting CTRCD were 0.694 and 0.707, respectively. CONCLUSIONS GLS changes among patients with subclinical impairment of cardiac function who were treated with fluorouracil-based chemotherapies, and C1v-LAEF and C1v-LASr of the left atrium are early predictors of cardiac function deterioration.
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Affiliation(s)
- Wei Yang
- State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jian-Xia Yang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jing-Yuan Guan
- State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Wu-Yun Bao
- State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Mei Zhang
- State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China.
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Hugelshofer S, Giacomuzzi-Moore B, Auberson D, Tzimas G, Kamani CH, Masi A, Monney P, Arangalage D, Poku NK. Multi-Modality Imaging to Detect Ischemic and Valvular Heart Disease in Adult Cancer Patients. Echocardiography 2024; 41:e70030. [PMID: 39539138 DOI: 10.1111/echo.70030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 10/21/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024] Open
Abstract
Thanks to impressive advances in the field of oncology over the last 30 years, there has been a significant rise in cancer survivors. Nowadays, cardiovascular disease is one of the leading causes of death in this patient population. Coronary artery disease (CAD) is a major problem due to shared risk factors, an aging population and in many cases induced and/or accelerated atherosclerosis by antitumoral treatment during and even decades after the end of cancer therapy. Furthermore, the presence of CAD or valvular heart disease (VHD) at the time point of cancer diagnosis largely increases the risk of any cancer therapy-related cardiovascular toxicity (CTR-CVT). It is therefore of utmost importance to detect CAD and VHD before, during, and after certain types of chemotherapy, target therapies, and radiotherapy. Multimodality cardiovascular imaging plays a central role in this vulnerable population where individual risk stratification and multidisciplinary decision-making are critical.
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Affiliation(s)
- Sarah Hugelshofer
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | | | - Denise Auberson
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Georgios Tzimas
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Christel H Kamani
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
- Department of Nuclear Medicine, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Ambra Masi
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Pierre Monney
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Dimitri Arangalage
- Cardiology Unit, Cardio-Vascular Department, University Hospital of Canton Vaud (CHUV), Lausanne, Switzerland
| | - Nana K Poku
- Cardiology Unit, Medical Department, University Hospital of Canton Geneva (HUG), Geneva, Switzerland
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Leiva O, Zarif TE, Alvarez-Cardona J. Gastrointestinal Cancer Therapy and Cardiotoxicity. Curr Treat Options Oncol 2024; 25:1203-1209. [PMID: 39102169 DOI: 10.1007/s11864-024-01236-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 08/06/2024]
Abstract
OPINION STATEMENT Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.
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Affiliation(s)
- Orly Leiva
- Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, U.S.A
| | - Talal El Zarif
- Department of Medicine, Yale New Haven Health, New Haven, CT, U.S.A
| | - Jose Alvarez-Cardona
- Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, U.S.A..
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Rajaeinejad M, Parhizkar-Roudsari P, Khoshfetrat M, Kazemi-Galougahi MH, Mosaed R, Arjmand R, Mohsenizadeh SA, Arjmand B. Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment. Cardiovasc Toxicol 2024; 24:184-198. [PMID: 38324115 DOI: 10.1007/s12012-024-09834-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 01/20/2024] [Indexed: 02/08/2024]
Abstract
Advancements in cancer treatments have improved survival rates but have also led to increased cardiotoxicities, which can cause adverse cardiovascular events or worsen pre-existing conditions. Herein, cardiotoxicity is a severe adverse effect of 5-fluorouracil (5-FU) therapy in cancer patients, with reported incidence rates ranging from 1 to 20%. Some studies have also suggested subclinical effects and there are reports which have documented instances of cardiac arrest or sudden death during 5-FU treatment, highlighting the importance of timely management of cardiovascular symptoms. However, despite being treated with conventional medical approaches for this cardiotoxicity, a subset of patients has demonstrated suboptimal or insufficient responses. The frequent use of 5-FU in chemotherapy and its association with significant morbidity and mortality indicates the need for a greater understanding of 5-FU-associated cardiotoxicity. It is essential to reduce the adverse effects of anti-tumor medications while preserving their efficacy, which can be achieved through drugs that mitigate toxicity associated with these drugs. Underpinning cardiotoxicity associated with 5-FU therapy also has the potential to offer valuable guidance in pinpointing pharmacological approaches that can be employed to prevent or ameliorate these effects. The present study provides an overview of management strategies for cardiac events induced by fluoropyrimidine-based cancer treatments. The review encompasses the underlying molecular and cellular mechanisms of cardiotoxicity, associated risk factors, and diagnostic methods. Additionally, we provide information on several available treatments and drug choices for angina resulting from 5-FU exposure, including nicorandil, ranolazine, trimetazidine, ivabradine, and sacubitril-valsartan, which have demonstrated potential in mitigating or protecting against chemotherapy-induced adverse cardiac effects.
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Affiliation(s)
- Mohsen Rajaeinejad
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Peyvand Parhizkar-Roudsari
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
- Iranian Cancer Control Center, Tehran, Iran
| | - Mehran Khoshfetrat
- Department of Cardiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | | | - Reza Mosaed
- Infection Diseases Research Center, AJA University of Medical Sciences, Tehran, Iran
- Student Research Committee, AJA University of Medical Sciences, Tehran, Iran
| | - Rasta Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Babak Arjmand
- Department of Internal Medicine, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
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Pushparaji B, Donisan T, Balanescu DV, Park JK, Monlezun DJ, Ali A, Inanc IH, Caballero J, Cilingiroglu M, Marmagkiolis K, Iliescu C. Coronary Revascularization in Patients With Cancer. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2023; 25:143-158. [PMID: 37143711 PMCID: PMC10119009 DOI: 10.1007/s11936-023-00982-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/21/2023] [Indexed: 05/06/2023]
Abstract
Purpose of review The treatment of coronary artery disease (CAD) in cancer patients is an evolving landscape. Recent data emphasizes the importance of aggressive management of cardiovascular risk factors and diseases in improving cardiovascular health in this unique group of patients regardless of cancer type or stage. Recent findings Novel cancer therapeutics such as immune therapies and proteasome inhibitors have been associated with CAD. Recent stent technologies may safely allow for shorter duration (< 6 months) of dual antiplatelet therapy post-percutaneous coronary interventions. Intracoronary imaging may be useful in the decision making process in terms of stent positioning and healing. Summary Large registry studies have partially filled a gap left by the lack of randomized controlled trials in the treatment of CAD in cancer patients. Cardio-oncology is gaining traction as a major sub-specialty in the cardiology field given the release of the first European Society of Cardiology - Cardio-oncology guidelines in 2022.
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Affiliation(s)
- Bala Pushparaji
- Department of Internal Medicine, Maimonides Medical Center, Brooklyn, NY USA
| | - Teodora Donisan
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN USA
| | | | - Jong Kun Park
- Deparment of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX USA
| | - Dominique J. Monlezun
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Abdelrahman Ali
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Ibrahim Halil Inanc
- Department of Cardiology, Kirikkale Research and Training Hospital, Kirikkale, Turkey
| | - Jaime Caballero
- Interventional Cardiology, Department of Internal Medicine, University of South Florida, Tampa, FL USA
| | - Mehmet Cilingiroglu
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | | | - Cezar Iliescu
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
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Lu Y, Pan W, Deng S, Dou Q, Wang X, An Q, Wang X, Ji H, Hei Y, Chen Y, Yang J, Zhang HM. Redefining the Incidence and Profile of Fluoropyrimidine-Associated Cardiotoxicity in Cancer Patients: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel) 2023; 16:ph16040510. [PMID: 37111268 PMCID: PMC10146083 DOI: 10.3390/ph16040510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/14/2023] [Accepted: 03/21/2023] [Indexed: 04/01/2023] Open
Abstract
Aim: The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. Methods: A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). Results: A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ2 = 10.15, p < 0.01; χ2 = 10.77, p < 0.01). The continuous 5-FU infusion for 3–5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. Conclusions: Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.
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Affiliation(s)
- Yajie Lu
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
- The State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Air Force Medical University, Xi’an 710032, China
- Correspondence: (Y.L.); (H.-M.Z.)
| | - Wei Pan
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Shizhou Deng
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Qiongyi Dou
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Xiangxu Wang
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Qiang An
- The Department of Biomedical Engineering, Air Force Medical University, Xi’an 710032, China
| | - Xiaowen Wang
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Hongchen Ji
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Yue Hei
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Yan Chen
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Jingyue Yang
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Hong-Mei Zhang
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
- Correspondence: (Y.L.); (H.-M.Z.)
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Lombardi P, Aimar G, Peraldo-Neia C, Bonzano A, Depetris I, Fenocchio E, Filippi R, Quarà V, Milanesio M, Cavalloni G, Gammaitoni L, Basiricò M, Cagnazzo C, Ostano P, Chiorino G, Aglietta M, Leone F. Fluoropyrimidine‑induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT). Oncol Rep 2022; 49:31. [PMID: 36562382 PMCID: PMC9827273 DOI: 10.3892/or.2022.8468] [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: 07/21/2022] [Accepted: 11/22/2022] [Indexed: 12/24/2022] Open
Abstract
Fluoropyrimidines (FP) are the backbone chemotherapy in colorectal cancer (CRC) treatment; however, their use is associated with cardiotoxicity, which is underreported. In the present study, it was aimed to prospectively determine the incidence rates and related risk factors of FP‑induced cardiotoxicity (FIC) in CRC patients and at identifying predictive biomarkers. A total of 129 consecutive previously untreated CRC patients underwent active cardiological monitoring, including 5‑items simplified questionnaire on symptoms, electrocardiogram (ECG) and plasma sample collection during FP chemotherapy. FIC was defined as the presence of ECG alterations and/or the arising of at least one symptom of chest pain, dyspnoea, palpitations or syncope. The primary objective was the evaluation of FIC incidence. Secondary objectives were the correlation of FIC with well‑known cardiological risk factors and the identification of circulating biomarkers (serum levels of troponin I, pro hormone BNP; miRNA analysis) as predictors of FIC. A total of 20 out of 129 (15.5%) patients experienced FIC. The most common symptoms were dyspnoea (60%) and chest pain (40%), while only 15% of patients presented ECG alterations, including one acute myocardial infarction. Retreatment with FP was attempted in 90% of patients with a favourable outcome. Despite 48% of patients having cardiological comorbidities, an increased FIC was not observed in this subgroup. Only the subgroup of females with the habit of alcohol consumption showed an increased risk of FIC. None of the circulating biomarkers evaluated demonstrated a clinical utility as FIC predictors. FIC can be an unexpected, life‑threatening adverse event that can limit the subsequent treatment choices in patients with CRC. In this prospective study, well‑known cardiological comorbidities were not related to higher FIC risk and circulating biomarkers predictive of toxicity could not be found. With careful monitoring, mainly based on symptoms, almost all patients completed the FP treatment.
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Affiliation(s)
- Pasquale Lombardi
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Phase 1 Unit, Agostino Gemelli Foundation University Hospital IRCCS, I-00168 Roma, Italy
| | - Giacomo Aimar
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Department of Oncology, S. Croce and Carle Hospital, I-12100 Cuneo, Italy
| | | | | | - Ilaria Depetris
- Division of Medical Oncology 1, AOU City of Health and Science of Turin, I-12126 Turin, Italy
| | - Elisabetta Fenocchio
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | - Roberto Filippi
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Division of Medical Oncology 1, AOU City of Health and Science of Turin, I-12126 Turin, Italy
| | - Virginia Quarà
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | | | - Giuliana Cavalloni
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | | | - Marco Basiricò
- Department of Public Health and Pediatric Sciences, AOU City of Health and Science of Turin, Regina Margherita Hospital, I-10126 Torino, Italy
| | - Celeste Cagnazzo
- Department of Public Health and Pediatric Sciences, AOU City of Health and Science of Turin, Regina Margherita Hospital, I-10126 Torino, Italy
| | - Paola Ostano
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, I-13900 Biella, Italy
| | - Giovanna Chiorino
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, I-13900 Biella, Italy
| | - Massimo Aglietta
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | - Francesco Leone
- Department of Medical Oncology, Infermi Hospital of Biella, Ponderano, I-13875 Biella, Italy,Correspondence to: Dr Francesco Leone, Department of Medical Oncology, Infermi Hospital of Biella, 2 Via dei Ponderanesi, Ponderano, I-13875 Biella, Italy, E-mail:
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Lu Y, Deng S, Dou Q, Pan W, Liu Q, Ji H, Wang X, Zhang HM. Treatment-Related Coronary Disorders of Fluoropyrimidine Administration: A Systematic Review and Meta-Analysis. Front Pharmacol 2022; 13:885699. [PMID: 35645806 PMCID: PMC9140752 DOI: 10.3389/fphar.2022.885699] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/07/2022] [Indexed: 12/02/2022] Open
Abstract
Background: Coronary disorders are recognized as the most common manifestation of fluoropyrimidine-related cardiotoxicity in clinical practice. However, there are limited and conflicting data on the incidence and profiles of fluoropyrimidine-related coronary disorders. In this meta-analysis, we aimed to systematically assess the incidence of all-grade and grade 3 or higher fluoropyrimidine-related coronary disorders, and further explore the factors that influence its occurrence. Methods: Studies reporting the fluoropyrimidine-related coronary disorders were retrieved from a systematic search of English literature in the PubMed, Web of Science, Medline, and Cochrane database from 1 Jan 2001, to 1 Jan 2022. The NIH assessment tool was used to evaluate the quality of each study. The data of basic study characteristics, treatment details, and results of coronary toxicities were extracted. According to the results of the heterogeneity test (I2 and p-value statistic), a random-effect model or fixed-effect model was selected for the pooled analysis of the incidence of adverse coronary events. Subgroup analysis was conducted to further explore the risks influencing the occurrence of fluoropyrimidine-related coronary disorders. The stability and publication bias of our results were evaluated by sensitivity analysis and Egger test, respectively. Results: A total of 63 studies were finally included in our pooled analysis, involving 25,577 patients. The pooled cumulative incidence of all-grade and grade 3 or higher coronary disorders was 2.75% (95% CI 1.89%–3.76%) and 1.00% (95% CI 0.62%–1.47%), respectively. The coronary disorders were most reported as myocardial ischemia (1.28%, 95% CI 0.42%–2.49%) and angina/chest pain (1.1%, 95% CI 0.54%–1.81%). Subgroup analysis revealed that studies in the female-only population seemed to have a lower incidence of fluoropyrimidine-related coronary disorders. The occurrence of adverse coronary events varied among different tumor types. Patients with esophageal cancer have the highest coronary toxicity (6.32%), while those with breast cancer have a relatively lower incidence (0.5%). Coronary disorders induced by 5-FU monotherapy are more frequent than that induced by capecitabine (3.31% vs. 1.21%, p < 0.01). Fluoropyrimidine combination therapy, whether combined with other chemotherapy drugs, targeted therapy drugs, or radiotherapy, significantly increased the incidence of coronary complications (p < 0.01). Conclusion: This meta-analysis has defined the incidence of fluoropyrimidine-related coronary disorders and depicted its epidemiological profiles for the first time, which may provide a reference for clinical practice in cancer management.
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Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022; 145:e895-e1032. [PMID: 35363499 DOI: 10.1161/cir.0000000000001063] [Citation(s) in RCA: 1074] [Impact Index Per Article: 358.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
AIM The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.
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Affiliation(s)
| | | | | | | | | | | | - Anita Deswal
- ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison
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10
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Shobayo F, Bajwa M, Koutroumpakis E, Hassan SA, Palaskas NL, Iliescu C, Abe JI, Mouhayar E, Karimzad K, Thompson KA, Deswal A, Yusuf S. Acute coronary syndrome in patients with cancer. Expert Rev Cardiovasc Ther 2022; 20:275-290. [PMID: 35412407 DOI: 10.1080/14779072.2022.2063840] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Improvement in cancer survival has led to an increased focus on cardiovascular disease as the other major determinant of survivorship. As a result, there has been an increasing interest in managing cardiovascular disease during and post cancer treatment. AREAS COVERED This article reviews the current literature on the pathogenesis, risk factors, presentation, treatment and clinical outcomes of acute coronary syndrome (ACS) in patients with cancer. EXPERT OPINION There is growing evidence that both medical therapy and invasive management of ACS improve outcomes in patients with cancer. Appropriate patient selection, risk stratification and tailored therapy represents the cornerstone of management in these patients.
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Affiliation(s)
- Fisayomi Shobayo
- Division of Cardiovascular Medicine, University of Texas Health Science Center, Houston, Texas, USA
| | - Muhammad Bajwa
- Division of Cardiovascular Medicine, University of Texas Health Science Center, Houston, Texas, USA
| | | | - Saamir A Hassan
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nicolas L Palaskas
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Cezar Iliescu
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jun-Ichi Abe
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Elie Mouhayar
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Kaveh Karimzad
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Kara A Thompson
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Anita Deswal
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Syed Yusuf
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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11
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Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol 2022; 79:e263-e421. [PMID: 35379503 DOI: 10.1016/j.jacc.2021.12.012] [Citation(s) in RCA: 1238] [Impact Index Per Article: 412.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. METHODS A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. STRUCTURE Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.
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12
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Anaka M, Abdel-Rahman O. Managing 5FU Cardiotoxicity in Colorectal Cancer Treatment. Cancer Manag Res 2022; 14:273-285. [PMID: 35115827 PMCID: PMC8799936 DOI: 10.2147/cmar.s273544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 01/11/2022] [Indexed: 11/28/2022] Open
Abstract
Fluorouracil (5FU) is the backbone chemotherapy agent in the treatment of colorectal cancer (CRC). Cardiotoxicity represents an uncommon but serious side effect of treatment with 5FU. Here, we review the current literature on 5FU-cardiotoxicity in the setting of CRC specifically, with a focus on data from the modern era of combination chemotherapy. Despite decades of study, there is little consensus on risk factors and biomarkers for 5FU-cardiotoxicity, nor how patients with CRC should be managed following a cardiotoxicity event. Given the elevated risk of recurrent cardiotoxicity on rechallenge, the use of alternative regimens that do not contain 5FU is a critical aspect of management. Data on the cardiotoxicity risk and efficacy of non-5FU regimens in CRC are therefore reviewed in detail.
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Affiliation(s)
- Matthew Anaka
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
- Correspondence: Omar Abdel-Rahman, Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada, Tel +1 780-432-8290, Fax +1 780-432-8888, Email
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13
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Viswanathan T, Lang CC, Petty RD, Baxter MA. Cardiotoxicity and Chemotherapy-The Role of Precision Medicine. Diseases 2021; 9:90. [PMID: 34940028 PMCID: PMC8699963 DOI: 10.3390/diseases9040090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/25/2021] [Accepted: 11/28/2021] [Indexed: 11/16/2022] Open
Abstract
Cancer and cardiovascular disease are the leading causes of death in the United Kingdom. Many systemic anticancer treatments are associated with short- and long-term cardiotoxicity. With improving cancer survival and an ageing population, identifying those patients at the greatest risk of cardiotoxicity from their cancer treatment is becoming a research priority and has led to a new subspecialty: cardio-oncology. In this concise review article, we discuss cardiotoxicity and systemic anticancer therapy, with a focus on chemotherapy. We also discuss the challenge of identifying those at risk and the role of precision medicine as we strive for a personalised approach to this clinical scenario.
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Affiliation(s)
- Thyla Viswanathan
- Dundee School of Medicine, Ninewells Hospital, University of Dundee, Dundee DD2 1SY, UK;
| | - Chim C. Lang
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee DD2 1SY, UK; (C.C.L.); (R.D.P.)
- UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia
| | - Russell D. Petty
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee DD2 1SY, UK; (C.C.L.); (R.D.P.)
- Tayside Cancer Centre, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD2 1SY, UK
| | - Mark A. Baxter
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee DD2 1SY, UK; (C.C.L.); (R.D.P.)
- Tayside Cancer Centre, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD2 1SY, UK
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14
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Gul I, Yunus U, Ajmal M, Bhatti MH, Chaudhry GES. Development of biodegradable thin films for efficient, specific and controlled delivery of capecitabine. Biomed Mater 2021; 16. [PMID: 34375958 DOI: 10.1088/1748-605x/ac1c61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/10/2021] [Indexed: 11/11/2022]
Abstract
Cancer is the leading cause of death worldwide. Capecitabine (CP) shows severe side effects because of early metabolism in stomach that affects the normal cells and organs, particularly liver and stomach. In this scope, we report the biocompatible, nontoxic polymeric thin films loaded with anti-cancer drug, CP for target specific, sublingual delivery of CP. Chitosan (CS) and polyvinyl alcohol (PVA) were used as biodegradable polymers alongwith glutaraldehyde (GLA) cross linker. CP-loaded thin films (TFCP1-TFCP5) were fabricated by solvent casting method. The results of Fourier transform infrared spectroscopy confirmed the presence of CP and polymers (CS and PVA) with GLA which binds through hydrogen bonding, and compatibility of drug with different excipients. Thermogravemetric analysis showed that the thin films are highly stable while differential scanning calorimeter thermograms confirmed the complete miscibility/entrapment of CP within PVA/CS thin film matrix. X-ray diffraction patterns revealed the molecular ineractions between CP and polymer matrix. High degree of swelling index of thin films at pH 7.4 was observed in comparison to pH 5.5. CP release studies in acetate (pH 5.5) and phosphate buffer (pH 7.4) showed that the thin films swell and result in drug diffusion faster in phosphate buffer through diffusion governed by Higuchi's model. Cytotoxicity results displayed that CPTFs killed MCF-7 and T47D (human breast adenocarcinoma) cells more effectively as compared to CP alone. The results of adhesion assay also showed that the PVA and CS both are safe and biocompatible. TFCP1 and TFCP3 thin films efficiently induced the apoptosis as compared to CP alone. The improved ability of TFCP1 and TFCP3 to induce cytotoxicity in MCF-7 cells reflects the potential of these thin films for targeted drug delivery. The CPTFs were stable for 4 months at 4 °C/60% ± 2%RH and 25 °C/70% ± 2%RH. In conclusion, the thin film formulations showed target specific controlled and burst release properties and thus could prove to be effective for human breast cancer treatment.
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Affiliation(s)
- Irum Gul
- Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
| | - Uzma Yunus
- Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
| | - Muhammad Ajmal
- Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
| | | | - Gul-E-Saba Chaudhry
- Institute of Marine Biotechnology, University Malaysia Terengganu, 21030 Kuala, Terengganu, Malaysia
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15
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García-Alfonso P, Muñoz Martín AJ, Ortega Morán L, Soto Alsar J, Torres Pérez-Solero G, Blanco Codesido M, Calvo Ferrandiz PA, Grasso Cicala S. Oral drugs in the treatment of metastatic colorectal cancer. Ther Adv Med Oncol 2021; 13:17588359211009001. [PMID: 33995592 PMCID: PMC8111515 DOI: 10.1177/17588359211009001] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/17/2021] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common forms of cancer, with an estimated 1.36 million new cases and almost 700,000 deaths annually. Approximately 21% of patients with CRC have metastatic disease at diagnosis. The objective of this article is to review the literature on the efficacy and safety of oral drugs available for the treatment of metastatic colorectal cancer (mCRC). Several such drugs have been developed, and fluoropyrimidines are the backbone of chemotherapy in this indication. They exert their antitumour activity by disrupting the synthesis and function of DNA and RNA. Oral fluoropyrimidines include prodrugs capecitabine, tegafur, eniluracil/5-fluorouracil, tegafur/uracil, tegafur/gimeracil/oteracil and trifluridine/tipiracil (FTD/TPI). Oral drugs offer several advantages over injectable formulations, including convenience, flexibility, avoidance of injection-related adverse events (AEs) and, in some circumstances, lower costs. However, oral drugs may not be suitable for patients with gastrointestinal obstruction or malabsorption, they may result in reduced treatment adherence and should not be co-administered with drugs that interfere with absorption or hepatic metabolism. Oral fluoropyrimidines such as capecitabine, as monotherapy or in combination with oxaliplatin, irinotecan or bevacizumab, are as effective as intravenous 5-fluorouracil (5-FU) in first-line treatment of mCRC. Other oral fluoropyrimidines, such as FTD/TPI, are effective in patients with mCRC who are refractory, intolerant or ineligible for 5-FU. In addition, oral fluoropyrimidines are used in adjuvant treatment of mCRC. Regorafenib is an oral multikinase inhibitor used in patients in whom several previous lines of therapy have failed. Frequent AEs associated with oral drugs used in the treatment of CRC include hand-foot syndrome and gastrointestinal and haematological toxicities.
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Affiliation(s)
- Pilar García-Alfonso
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, Madrid, 28009, Spain
| | | | - Laura Ortega Morán
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Javier Soto Alsar
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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16
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McAndrew EN, Jassal DS, Goldenberg BA, Kim CA. Capecitabine-mediated heart failure in colorectal cancer: a case series. Eur Heart J Case Rep 2021; 5:ytab079. [PMID: 33709051 PMCID: PMC7936921 DOI: 10.1093/ehjcr/ytab079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/28/2020] [Accepted: 02/04/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Capecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is commonly used in the treatment of colorectal cancer. Adverse cardiac side effects are reported in 1-18% of patients receiving Capecitabine. The most commonly proposed mechanism of cardiotoxicity in the setting of Capecitabine use is vasospasm of the coronary arteries. However, cardiotoxicity can also present as an acute coronary syndrome, arrhythmia, hypertension, and/or sudden cardiac death. Profound non-vasospastic cardiotoxicity is rare. CASE SUMMARY We describe two cases of acute heart failure leading to cardiogenic shock in patients shortly after exposure to Capecitabine. Both patients did not demonstrate the characteristic transient ST elevation seen in patients with coronary artery vasospasms secondary to Capecitabine. Both patients required admission to the Acute Cardiac Care Unit requiring vasopressor and inotropic support. Thorough diagnostic investigations including echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography did not identify infarction, myocarditis, or any infiltrative process to explain their symptoms. Both patients had complete resolution of cardiac function, with no long-term sequalae. DISCUSSION In patients receiving Capecitabine, reversible heart failure leading to cardiogenic shock should be considered as a potential cardiotoxic side effect.
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Affiliation(s)
- Erin N McAndrew
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Davinder S Jassal
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Radiology, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Benjamin A Goldenberg
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Medical Oncology and Haematology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 409 Tache Ave, Winnipeg, Manitoba R2H 2A6, Canada
| | - Christina A Kim
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Medical Oncology and Haematology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 409 Tache Ave, Winnipeg, Manitoba R2H 2A6, Canada
- Research Institute in Oncology and Hematology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
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17
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Lisby AN, Flickinger JC, Bashir B, Weindorfer M, Shelukar S, Crutcher M, Snook AE, Waldman SA. GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2021; 6:117-129. [PMID: 34027103 DOI: 10.1080/23808993.2021.1876518] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction Colorectal cancer (CRC) is one of the most-deadly malignancies worldwide. Current therapeutic regimens for CRC patients are relatively generic, based primarily on disease type and stage, with little variation. As the field of molecular oncology advances, so too must therapeutic management of CRC. Understanding molecular heterogeneity has led to a new-found promotion for precision therapy in CRC; underlining the diversity of molecularly targeted therapies based on individual tumor characteristics. Areas covered We review current approaches for the treatment of CRC and discuss the potential of precision therapy in advanced CRC. We highlight the utility of the intestinal protein guanylyl cyclase C (GUCY2C), as a multi-purpose biomarker and unique therapeutic target in CRC. Here, we summarize current GUCY2C-targeted approaches for treatment of CRC. Expert opinion The GUCY2C biomarker has multi-faceted utility in medicine. Developmental investment of GUCY2C as a diagnostic and therapeutic biomarker offers a variety of options taking the molecular characteristics of cancer into account. From GUCY2C-targeted therapies, namely cancer vaccines, CAR-T cells, and monoclonal antibodies, to GUCY2C agonists for chemoprevention in those who are at high risk for developing colorectal cancer, the utility of this protein provides many avenues for exploration with significance in the field of precision medicine.
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Affiliation(s)
- Amanda N Lisby
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - John C Flickinger
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Babar Bashir
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Megan Weindorfer
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Sanjna Shelukar
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Madison Crutcher
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Adam E Snook
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Scott A Waldman
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, United States
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18
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Matthews AA, Peacock Hinton S, Stanway S, Lyon AR, Smeeth L, Bhaskaran K, Lund JL. Risk of Cardiovascular Diseases Among Older Breast Cancer Survivors in the United States: A Matched Cohort Study. J Natl Compr Canc Netw 2021; 19:275-284. [PMID: 33401236 DOI: 10.6004/jnccn.2020.7629] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 07/24/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND It has been suggested that cardiovascular risks are increased in breast cancer survivors, but few studies have quantified the risks of a range of specific clinically important cardiovascular outcomes in detail. PATIENTS AND METHODS Women aged >65 years with incident breast cancer from 2004 to 2013 in the SEER-Medicare linked database were matched with 5 cancer-free female counterparts (5:1 ratio). Prevalence of specific cardiovascular outcomes at baseline was measured, then Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of individual cardiovascular outcomes during follow-up. Modification of the effect was investigated by time since diagnosis, race/ethnicity, prior cardiovascular disease (CVD), and age. RESULTS In all, 91,473 women with breast cancer and 454,197 without breast cancer were included. Women with breast cancer had lower baseline prevalence of all CVDs. Compared with cancer-free controls, breast cancer survivors had substantially increased risks of deep vein thrombosis (adjusted HR, 1.67; 95% CI, 1.62-1.73; 386,484 person-years of follow-up) and pericarditis (HR, 1.43; 95% CI, 1.38-1.49; 390,776 person-years of follow-up); evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease (adjusted HRs ranging from 1.05-1.09, lower CI limits all ≥1); and evidence of lower risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke (adjusted HRs ranging from 0.89-0.98, upper CI limits all ≤1). Increased risks of arrhythmia, heart failure, pericarditis, and deep vein thrombosis persisted >5 years after cancer diagnosis. CONCLUSIONS Women with a history of breast cancer were at increased risk of several CVDs, persisting into survivorship. Monitoring and managing cardiovascular risk throughout the long-term follow-up of women diagnosed with breast cancer should be a priority.
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Affiliation(s)
- Anthony A Matthews
- 1Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.,2Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,3Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and
| | - Sharon Peacock Hinton
- 2Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | | | - Alexander R Lyon
- 5National Heart and Lung Institute, Imperial College London, and.,6Royal Brompton Hospital, London, United Kingdom
| | - Liam Smeeth
- 1Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Krishnan Bhaskaran
- 1Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Jennifer L Lund
- 2Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Piroth MD, Krug D, Sedlmayer F, Duma MN, Baumann R, Budach W, Dunst J, Feyer P, Fietkau R, Haase W, Harms W, Hehr T, Souchon R, Strnad V, Sauer R. Post-neoadjuvant treatment with capecitabine and trastuzumab emtansine in breast cancer patients-sequentially, or better simultaneously? Strahlenther Onkol 2021; 197:1-7. [PMID: 32737515 PMCID: PMC7801351 DOI: 10.1007/s00066-020-01667-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 07/01/2020] [Indexed: 10/27/2022]
Abstract
PURPOSE Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen. METHODS A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness. RESULTS Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T‑DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed. CONCLUSION Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T‑DM1 can safely be administered concurrently with radiotherapy.
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Affiliation(s)
- Marc D. Piroth
- Dpt. of Radiation Oncology, Wuppertal University Hospital (Helios), Witten/Herdecke University, Heusnerstraße 40, 42283 Wuppertal, Germany
| | - David Krug
- University Hospital Schleswig-Holstein, Kiel, Germany
| | - Felix Sedlmayer
- Paracelsus Medical University Hospital Salzburg, Salzburg, Austria
| | | | | | - Wilfried Budach
- Heinrich-Heine-University Hospital Düsseldorf, Düsseldorf, Germany
| | - Jürgen Dunst
- University Hospital Schleswig-Holstein, Kiel, Germany
| | - Petra Feyer
- Vivantes Hospital Neukoelln, Berlin, Germany
| | | | - Wulf Haase
- formerly St.-Vincentius-Hospital Karlsruhe, Karlsruhe, Germany
| | | | - Thomas Hehr
- Marienhospital Stuttgart, Stuttgart, Germany
| | | | | | - Rolf Sauer
- University Hospital Erlangen, Erlangen, Germany
| | - Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)
- Dpt. of Radiation Oncology, Wuppertal University Hospital (Helios), Witten/Herdecke University, Heusnerstraße 40, 42283 Wuppertal, Germany
- University Hospital Schleswig-Holstein, Kiel, Germany
- Paracelsus Medical University Hospital Salzburg, Salzburg, Austria
- Friedrich-Schiller-University Hospital Jena, Jena, Germany
- St. Marien-Krankenhaus Siegen, Siegen, Germany
- Heinrich-Heine-University Hospital Düsseldorf, Düsseldorf, Germany
- Vivantes Hospital Neukoelln, Berlin, Germany
- University Hospital Erlangen, Erlangen, Germany
- formerly St.-Vincentius-Hospital Karlsruhe, Karlsruhe, Germany
- St. Claraspital Basel, Basel, Switzerland
- Marienhospital Stuttgart, Stuttgart, Germany
- formerly University Hospital, Tübingen, Germany
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20
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Ruddy KJ, Patel SR, Higgins AS, Armenian SH, Herrmann J. Cardiovascular Health during and after Cancer Therapy. Cancers (Basel) 2020; 12:E3737. [PMID: 33322622 PMCID: PMC7763346 DOI: 10.3390/cancers12123737] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 01/22/2023] Open
Abstract
Certain cancer treatments have been linked to specific cardiovascular toxicities, including (but not limited to) cardiomyopathy, atrial fibrillation, arterial hypertension, and myocarditis. Radiation, anthracyclines, human epidermal growth factor receptor 2 (Her2)-directed therapies, fluoropyrimidines, platinums, tyrosine kinase inhibitors and proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen-presenting (CAR)-T cell therapy can all cause cardiovascular side effects. Management of cardiovascular dysfunction that occurs during cancer therapy often requires temporary or permanent cessation of the risk-potentiating anti-neoplastic drug as well as optimization of medical management from a cardiovascular standpoint. Stem cell or bone marrow transplant recipients face unique cardiovascular challenges, as do patients at extremes of age.
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Affiliation(s)
| | - Shruti R. Patel
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | | | - Saro H. Armenian
- Department of Population Sciences, City of Hope, Duarte, CA 91010, USA;
| | - Joerg Herrmann
- Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN 55905, USA;
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21
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Dent SF, Kikuchi R, Kondapalli L, Ismail-Khan R, Brezden-Masley C, Barac A, Fradley M. Optimizing Cardiovascular Health in Patients With Cancer: A Practical Review of Risk Assessment, Monitoring, and Prevention of Cancer Treatment-Related Cardiovascular Toxicity. Am Soc Clin Oncol Educ Book 2020; 40:1-15. [PMID: 32213102 DOI: 10.1200/edbk_286019] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment-related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment-related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.
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Affiliation(s)
- Susan F Dent
- Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC
| | - Robin Kikuchi
- Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC
| | - Lavanya Kondapalli
- University of Colorado Health Cancer, University of Colorado, Aurora, CO
| | | | | | - Ana Barac
- MedStar Heart and Vascular Institute, Georgetown University, Washington, DC
| | - Michael Fradley
- Moffitt Cancer Center, University of South Florida, Tampa, FL
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22
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Saif MW. Alternative Treatment Options in Patients with Colorectal Cancer Who Encounter Fluoropyrimidine-Induced Cardiotoxicity. Onco Targets Ther 2020; 13:10197-10206. [PMID: 33116601 PMCID: PMC7553662 DOI: 10.2147/ott.s264156] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 09/07/2020] [Indexed: 12/03/2022] Open
Abstract
5-Fluorouracil (5-FU) remains to be the backbone of chemotherapy regimens approved for treatment of colorectal cancer and other gastrointestinal cancers and breast cancer. The incidence of cardiotoxicity associated with 5-FU ranges from 1.5-18%. Previous studies also concluded that rechallenging a patient with previous 5-FU cardiotoxicity with either lower dose or another mode of administration could result in repeat of cardiac complication in up to 45% of patients. Nearly 13% of patients died upon re-exposure to 5-FU. Clinical manifestations of cardiac complications of fluoropyrimidines including angina, myocardial infarction, arrhythmias, hypotension, Tako-Tsubo syndrome, heart failure, cardiogenic shock, pericarditis, and even sudden death have been reported. Cardiotoxicity is unpredictable and no alternative chemotherapeutics have been defined so far. The author describes here treatment options for patients with metastatic colorectal cancer who have encountered fluoropyrimidine-induced cardiotoxicity, including switching to a different fluoropyrimidine, switching to a different schedule of intravenous 5-FU, or switching to a non-fluoropyrimidine-containing chemotherapy regimen if one exists. Switching to a non-fluoropyrimidine-containing chemotherapy regimen is usually the most feasible choice for patients with metastatic disease as data on adjuvant setting is usually a fluoropyrimidine or its combination with oxaliplatin at present.
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Affiliation(s)
- Muhammad Wasif Saif
- NorthwellHealth Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra, Feinstein Institute for Medical Research, Lake Success, New York, NY, USA
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23
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Trapani D, Zagami P, Nicolò E, Pravettoni G, Curigliano G. Management of Cardiac Toxicity Induced by Chemotherapy. J Clin Med 2020; 9:E2885. [PMID: 32906611 PMCID: PMC7565686 DOI: 10.3390/jcm9092885] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/03/2020] [Accepted: 09/04/2020] [Indexed: 01/11/2023] Open
Abstract
Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.
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Affiliation(s)
- Dario Trapani
- European Institute of Oncology, IRCCS, 20141 Milan, Italy; (D.T.); (P.Z.); (E.N.); (G.P.)
| | - Paola Zagami
- European Institute of Oncology, IRCCS, 20141 Milan, Italy; (D.T.); (P.Z.); (E.N.); (G.P.)
- Department of Oncology and Hematology (DIPO), University of Milan, 20122 Milan, Italy
| | - Eleonora Nicolò
- European Institute of Oncology, IRCCS, 20141 Milan, Italy; (D.T.); (P.Z.); (E.N.); (G.P.)
- Department of Oncology and Hematology (DIPO), University of Milan, 20122 Milan, Italy
| | - Gabriella Pravettoni
- European Institute of Oncology, IRCCS, 20141 Milan, Italy; (D.T.); (P.Z.); (E.N.); (G.P.)
- Department of Oncology and Hematology (DIPO), University of Milan, 20122 Milan, Italy
| | - Giuseppe Curigliano
- European Institute of Oncology, IRCCS, 20141 Milan, Italy; (D.T.); (P.Z.); (E.N.); (G.P.)
- Department of Oncology and Hematology (DIPO), University of Milan, 20122 Milan, Italy
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24
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Batra A, Rigo R, Sheka D, Cheung WY. Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer. World J Gastrointest Oncol 2020; 12:604-618. [PMID: 32699576 PMCID: PMC7340998 DOI: 10.4251/wjgo.v12.i6.604] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/08/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Colon cancer represents one of the most common cancers diagnosed in older adults worldwide. The standard of care in resected stage II and stage III colon cancer continues to evolve. While there is unequivocal evidence to suggest both disease free and overall survival benefits with the use of combination chemotherapy in patients with stage III colon cancer, data regarding its use in patients with stage II colon cancer are less clear. Further, although colon cancer is a disease that affects older adults, there is considerable debate on the value of adjuvant chemotherapy in the aging population. In particular, many older patients are undertreated when compared to their younger counterparts. In this review, we will describe the clinical trials that contributed to the current adjuvant chemotherapy approach in colon cancer, discuss representation of older adults in trials and the specific challenges associated with the management of this sub-population, and highlight the role of comprehensive geriatric assessments. We will also review how real-world evidence complements the data gaps from clinical trials of early stage colon cancer.
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Affiliation(s)
- Atul Batra
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Rodrigo Rigo
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Dropen Sheka
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Winson Y Cheung
- Department of Oncology, University of Calgary, Calgary, Alberta T2N 4N2, Canada
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25
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Dyhl-Polk A, Vaage-Nilsen M, Schou M, Vistisen KK, Lund CM, Kümler T, Appel JM, Nielsen DL. Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer. Acta Oncol 2020; 59:475-483. [PMID: 31931649 DOI: 10.1080/0284186x.2019.1711164] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.
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Affiliation(s)
- Anne Dyhl-Polk
- Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Merete Vaage-Nilsen
- Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | - Morten Schou
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | | | - Cecilia Margareta Lund
- Department of Medicine, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | - Thomas Kümler
- Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | - Jon Michael Appel
- Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | - Dorte Lisbet Nielsen
- Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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26
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Abstract
OPINION STATEMENT Fluoropyrimidine (FP) is used to treat a wide range of cancers; however, it is associated with drug-induced vascular toxicity, as well as angina pectoris and coronary spasm. FP has been administered for many years, although the incidence, mechanisms, and appropriate methods for managing its associated cardiovascular toxicities have not been clarified, and the management of these complications has not been standardized. This lack of evidence is not limited to FP. Many trials of anticancer agents have been conducted, excluding patients with heart diseases. Hence, there is a paucity of epidemiological data on cardiovascular adverse events caused by anticancer agents. There have been remarkable improvements in cancer treatment in recent years, with consequent improvements in prognosis. In this context, new cardiovascular toxicities related to new drugs have emerged. We are now compelled to respond to cardiovascular adverse events despite the lack of evidence regarding optimal management. The result has been establishment and rapid maturation of the new academic field of cardio-oncology. Despite the relative lack of evidence, we must review small pieces of evidence that have accumulated to date and make the utmost efforts to provide patients with effective evidence-based medical care. Simultaneously, we urgently need randomized clinical trials to build strong evidence.
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Affiliation(s)
- Taro Shiga
- Department of Onco-Cardiology/Cardiovascular Medicine, The Cancer Institute Hospital Of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Makoto Hiraide
- Department of Pharmacy, The Cancer Institute Hospital Of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
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27
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Tocchetti CG, Cadeddu C, Di Lisi D, Femminò S, Madonna R, Mele D, Monte I, Novo G, Penna C, Pepe A, Spallarossa P, Varricchi G, Zito C, Pagliaro P, Mercuro G. From Molecular Mechanisms to Clinical Management of Antineoplastic Drug-Induced Cardiovascular Toxicity: A Translational Overview. Antioxid Redox Signal 2019; 30:2110-2153. [PMID: 28398124 PMCID: PMC6529857 DOI: 10.1089/ars.2016.6930] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity. Future Directions: Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system.
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Affiliation(s)
| | - Christian Cadeddu
- 2 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Daniela Di Lisi
- 3 Biomedical Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - Saveria Femminò
- 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Rosalinda Madonna
- 5 Center of Aging Sciences and Translational Medicine - CESI-MeT, "G. d'Annunzio" University, Chieti, Italy.,6 Department of Internal Medicine, The Texas Heart Institute and Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Houston, Texas
| | - Donato Mele
- 7 Cardiology Unit, Emergency Department, University Hospital of Ferrara, Ferrara, Italy
| | - Ines Monte
- 8 Department of General Surgery and Medical-Surgery Specialities, University of Catania, Catania, Italy
| | - Giuseppina Novo
- 3 Biomedical Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - Claudia Penna
- 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Alessia Pepe
- 9 U.O.C. Magnetic Resonance Imaging, Fondazione Toscana G. Monasterio C.N.R., Pisa, Italy
| | - Paolo Spallarossa
- 10 Clinic of Cardiovascular Diseases, IRCCS San Martino IST, Genova, Italy
| | - Gilda Varricchi
- 1 Department of Translational Medical Sciences, Federico II University, Naples, Italy.,11 Center for Basic and Clinical Immunology Research (CISI) - Federico II University, Naples, Italy
| | - Concetta Zito
- 12 Division of Cardiology, Clinical and Experimental Department of Medicine and Pharmacology, Policlinico "G. Martino" University of Messina, Messina, Italy
| | - Pasquale Pagliaro
- 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Giuseppe Mercuro
- 2 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
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Incidence of and risk factors for cardiotoxicity after fluorouracil-based chemotherapy in locally advanced or metastatic gastric cancer patients. Cancer Chemother Pharmacol 2019; 84:599-607. [DOI: 10.1007/s00280-019-03888-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 06/06/2019] [Indexed: 12/28/2022]
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29
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Chong JH, Ghosh AK. Coronary Artery Vasospasm Induced by 5-fluorouracil: Proposed Mechanisms, Existing Management Options and Future Directions. ACTA ACUST UNITED AC 2019; 14:89-94. [PMID: 31178935 PMCID: PMC6545978 DOI: 10.15420/icr.2019.12] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 04/17/2019] [Indexed: 12/13/2022]
Abstract
Cardiovascular disease and cancer are leading contributors to the global disease burden. As a result of cancer therapy-related cardiotoxicities, cardiovascular disease results in significant morbidity and mortality in cancer survivors and patients with active cancer. There is an unmet need for management of cardio-oncology conditions, which is predicted to reach epidemic proportions, and better understanding of their pathophysiology and treatment is urgently required. The proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) are vascular endothelial damage followed by thrombus formation, ischaemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischaemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischaemic symptoms. However, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed. While pre-existing coronary artery disease may increase the ischaemic potential of 5-FU, cardiovascular risk factors do not appear to completely predict the development of cardiac complications. Pharmacogenomic studies and genetic profiling may help predict the occurrence and streamline the treatment of 5-FU-induced coronary artery vasospasm. Echocardiographic measures such as the Tei index may help detect subclinical 5-FU cardiotoxicity. Further research is required to explore the cardioprotective effect of agents such as coenzyme complex, GLP-1 analogues and degradation inhibitors on 5-FU-induced coronary artery vasospasm.
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Affiliation(s)
- Jun Hua Chong
- Cardio-Oncology Service, Barts Heart Centre, St Bartholomew's Hospital London, UK
| | - Arjun K Ghosh
- Cardio-Oncology Service, Barts Heart Centre, St Bartholomew's Hospital London, UK.,Cardio-Oncology Service, University College London Hospital, Hatter Cardiovascular Institute London, UK
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30
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Chakrabarti S, Sara J, Lobo R, Eiring R, Finnes H, Mitchell J, Hartgers M, Okano A, Halfdanarson T, Grothey A. Bolus 5-fluorouracil (5-FU) In Combination With Oxaliplatin Is Safe and Well Tolerated in Patients Who Experienced Coronary Vasospasm With Infusional 5-FU or Capecitabine. Clin Colorectal Cancer 2019; 18:52-57. [PMID: 30396850 DOI: 10.1016/j.clcc.2018.09.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 09/14/2018] [Accepted: 09/17/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Coronary vasospasm associated with fluoropyrimidine (FP)-based chemotherapy is a potentially serious complication and reported to occur more often with infusional 5-fluorouracil (5-FU) or capecitabine than with bolus 5-FU. Given the additional benefit of oxaliplatin over FP alone in the management of colorectal cancer, retaining oxaliplatin in the treatment regimen is desirable, but the safety of combining bolus 5-FU with oxaliplatin in patients with FP-induced vasospasm is not well established. We performed a retrospective review to explore the safety of substituting FLOX (bolus 5-FU, oxaliplatin, leucovorin) for FOLFOX (infusional 5-FU, oxaliplatin, leucovorin) and CAPOX (capecitabine, oxaliplatin) in patients who had FP-induced coronary vasospasm. PATIENTS AND METHODS The pharmacy database of Mayo Clinic was queried to identify patients who developed coronary vasospasm associated with FOLFOX or CAPOX between January 2011 and January 2018 and were subsequently treated with FLOX. Detailed information was obtained on these patients by retrospective electronic chart review. RESULTS A total of 10 patients (median age, 56.5 years; range, 36-77 years) were identified, 9 with FOLFOX and 1 with CAPOX. Among the patients treated with FOLFOX, 8 patients had chest pain as the presenting complaint that had started within 48 hours of beginning of the 5-FU infusion. In 9 of 10 patients, coronary vasospasm occurred with the first cycle of therapy. All patients made full recovery after discontinuation of infusional 5-FU or capecitabine. All patients subsequently received FLOX with 7 median bolus 5-FU doses (range, 2-22 doses) and 7 median oxaliplatin doses (range, 2-12 doses) at 7 days to 18 months after the event, with 7 patients treated within 4 weeks of the event. FLOX did not cause any cardiovascular adverse events in any of the 10 patients. CONCLUSION Bolus 5-FU in combination with oxaliplatin is safe in patients who have experienced coronary vasospasm with infusional 5-FU or capecitabine.
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Affiliation(s)
| | - Jaskanwal Sara
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | - Ronstan Lobo
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | - Rachel Eiring
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | - Heidi Finnes
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | | | - Mindy Hartgers
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | - Akiko Okano
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
| | | | - Axel Grothey
- Department of Medical Oncology, Mayo Clinic, Rochester, MN
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31
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Abdel-Rahman O. 5-Fluorouracil-related Cardiotoxicity; Findings From Five Randomized Studies of 5-Fluorouracil-based Regimens in Metastatic Colorectal Cancer. Clin Colorectal Cancer 2019; 18:58-63. [DOI: 10.1016/j.clcc.2018.10.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 10/16/2018] [Accepted: 10/25/2018] [Indexed: 10/27/2022]
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Peng T, Ouyang Y, Tong K. Rechallenge capecitabine after fluoropyrimidine-induced cardiotoxicity in rectal cancer: A case report. Medicine (Baltimore) 2019; 98:e14057. [PMID: 30633206 PMCID: PMC6336628 DOI: 10.1097/md.0000000000014057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
RATIONALE Fluoropyrimidine-induced cardiotoxicity is a rare but potentially serious toxicity. The most common symptom is anginal chest pain. PATIENT CONCERNS A 35-year-old woman was diagnosed with rectal cancer with metastasis to the liver. DIAGNOSIS A computed tomography scan showed a 9.3 × 4.5-cm predominantly hypodense lesion within the left lobe of the liver and thickening of the rectum. Liver biopsy showed moderately differentiated adenocarcinoma with necrosis involving the liver parenchyma, and immunohistochemistry for mismatch repair proteins indicated that the tumor was positive for MutL Homolog 1, MutS Homolog 2, MutS Homolog 6, and Protein Homolog 2. Rectal biopsy indicated moderately differentiated adenocarcinoma. INTERVENTIONS She received chemotherapy of fluorouracil 1600 mg/m, leucovorin 500 mg/m, and irinotecan 100 mg/m every week. During the second cycle of chemotherapy, she developed severe anginal chest pain. We replaced fluorouracil with capecitabine 1500 mg (3 pills) a day every 2 weeks, with 1 week off, with irinotecan 100 mg/m on day 1 and bevacizumab 5 mg/kg at 200 ml/h for 30 min every 2 weeks. She was treated with chemotherapy for approximately 6 months. OUTCOMES The liver lesion showed a significant response to chemotherapy, so she underwent resection of the liver tumor and rectum. After the surgery, she received radiation therapy to the rectal area, and 3 months of chemotherapy were administered prior to colostomy reversal. LESSONS Although the mechanism of fluoropyrimidine-induced cardiotoxicity is still uncertain, our case provides clinical evidence that cardiotoxicity could be a dose-related complication. Reducing the dose of fluoropyrimidine should be considered as a strategy after fluoropyrimidine-induced cardiotoxicity. However, this must be discussed with a multidisciplinary team including oncologists and cardiologists. Close monitoring of serial biomarkers and echocardiography are necessary for early diagnosis of cardiotoxicity.
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Silva JMD, Lima BDS, Araújo TLD, Lima FET, Cunha GHD. Cardiovascular adverse events associated with oral antineoplastic therapy. Rev Bras Enferm 2018; 71:2561-2569. [PMID: 30304190 DOI: 10.1590/0034-7167-2017-0450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 10/18/2017] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE To identify in the literature the cardiovascular adverse events resulting from oral antineoplastic therapy. METHOD Integrative review of the literature through the SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE) databases. The antineoplastic, cardiotoxicity, cardiovascular system and adverse reaction descriptors were used in Portuguese, English and Spanish. We selected 23 articles published between 1985 and 2015. RESULTS Twenty studies were related to cardiac events and eleven to peripheral vascular events. The most frequent adverse cardiac events were reduced left ventricular ejection fraction, myocardial infarction, changes in the electrocardiogram, heart failure and angina, whereas peripheral vascular events were hypertension and thromboembolism. CONCLUSION Oral antineoplastic therapy is associated with different adverse events, including cardiac and peripheral vascular events.
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Affiliation(s)
- Jacqueline Mota da Silva
- Universidade Federal do Ceará, Faculty of Pharmacy, Dentistry and Nursing, Department of Nursing. Fortaleza, Ceará, Brazil
| | - Beatriz da Silva Lima
- Universidade Federal do Ceará, Faculty of Pharmacy, Dentistry and Nursing, Department of Nursing. Fortaleza, Ceará, Brazil
| | - Thelma Leite de Araújo
- Universidade Federal do Ceará, Faculty of Pharmacy, Dentistry and Nursing, Department of Nursing. Fortaleza, Ceará, Brazil
| | | | - Gilmara Holanda da Cunha
- Universidade Federal do Ceará, Faculty of Pharmacy, Dentistry and Nursing, Department of Nursing. Fortaleza, Ceará, Brazil
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Vaflard P, Ederhy S, Torregrosa C, André T, Cohen R, Lopez-Trabada D. [Fluoropyrimidines cardiac toxicity: 5-fluorouracil, capecitabine, compound S-1 and trifluridine/tipiracil]. Bull Cancer 2018; 105:707-719. [PMID: 29960638 DOI: 10.1016/j.bulcan.2018.05.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 05/03/2018] [Accepted: 05/06/2018] [Indexed: 10/28/2022]
Abstract
The incidence of cardiac toxicity of 5-flurorouracil (5-FU) IV and capecitabine varies from 1.2 to 18%. The physiopathology of this toxicity is still under study, various hypotheses are mentioned. In the absence of identified prophylactic treatment, reintroduction of this cytotoxic is at risk. A discussion between oncologists and cardiologists is essential to estimate the balance between benefit and risk and the careful reintroduction of treatment. An alternative compound might be raltitrexed which is currently the treatment recommended in case of intolerance to fluoropyrimidines. The compound S-1 does not have any cardiac toxicity. Of a total of 2910 patients in phase II or III studies, no grade III or IV cardiovascular events were reported. However, the treatment is not reimbursed in France and therefore not available. The trifluridine/tipiracil, for which approval from French authorities was obtained in November 2016 for patients with metastatic colorectal cancer in progress despite standard treatment lines, does not appear to have cardiac toxicity according to studies published to date. The pivotal phase III study (RECOURSE), that led to this marketing authorization, was performed in 800 patients with metastatic colorectal cancer refractory and only one patient (less than 1% of patients) treated with trifluridine/tipiracil presented an episode of cardiac ischemia. Thus, trifluridine/tipiracil, which is well tolerated, could be an alternative to raltitrexed for patients with cardiovascular history contraindicating or discouraging the use of fluoropyrimidines.
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Affiliation(s)
- Pauline Vaflard
- AP-HP, hôpital Saint-Antoine, département d'oncologie médicale, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Stéphane Ederhy
- AP-HP, hôpital Saint-Antoine, service de cardiologie, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Cécile Torregrosa
- UMPC Paris 06, Sorbonne université, 4, place Jussieu, 75005 Paris, France
| | - Thierry André
- AP-HP, hôpital Saint-Antoine, département d'oncologie médicale, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; AP-HP, hôpital Saint-Antoine, service de cardiologie, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; UMPC Paris 06, Sorbonne université, 4, place Jussieu, 75005 Paris, France
| | - Romain Cohen
- AP-HP, hôpital Saint-Antoine, département d'oncologie médicale, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; AP-HP, hôpital Saint-Antoine, service de cardiologie, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; UMPC Paris 06, Sorbonne université, 4, place Jussieu, 75005 Paris, France
| | - Daniel Lopez-Trabada
- AP-HP, hôpital Saint-Antoine, département d'oncologie médicale, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.
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Babiker HM, McBride A, Newton M, Boehmer LM, Drucker AG, Gowan M, Cassagnol M, Camenisch TD, Anwer F, Hollands JM. Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system. Crit Rev Oncol Hematol 2018; 126:186-200. [DOI: 10.1016/j.critrevonc.2018.03.014] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 02/01/2018] [Accepted: 03/21/2018] [Indexed: 11/16/2022] Open
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Peng J, Dong C, Wang C, Li W, Yu H, Zhang M, Zhao Q, Zhu B, Zhang J, Li W, Wang F, Wu Q, Zhou W, Yuan Y, Qiu M, Chen G. Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study. Cancer Commun (Lond) 2018; 38:22. [PMID: 29764506 PMCID: PMC5953402 DOI: 10.1186/s40880-018-0292-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 12/27/2017] [Indexed: 02/05/2023] Open
Abstract
Background 5-Fluorouracil (5-FU) and capecitabine-associated cardiotoxicity ranging from asymptomatic electrocardiography (ECG) abnormalities to severe myocardial infarction has been reported in a number of studies, but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date. In the present study, we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU- and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China. Methods Among the 527 patients who completed the study, 196 received 5-FU-based chemotherapy and 331 received capecitabine-based chemotherapy as either first-line or adjuvant therapy. Adverse events were reported during the treatment and up to 28 days of follow-up. Outcome measures included ECG, myocardial enzymes, cardiac troponin, brain natriuretic peptide and echocardiography. Univariate analysis and logistic regression were performed for subgroup analysis and identification of significant independent variables that are associated with cardiotoxicity of both agents. Results In total, 161 of 527 patients (30.6%) experienced cardiotoxicity. The incidence rate of cardiotoxicity was 33.8% (112/331) in the capecitabine group, which was significantly higher than the rate of 25% (49/196) in the 5-FU group (P = 0.0042). 110/527 patients (20.9%) suffered arrhythmia, 105/527 (19.9%) developed ischemic changes, while only 20/527 patients (3.8%) presented heart failure and 6/527 patients (1.1%) had myocardial infarction. Pre-existing cardiac disease, hypertension, capecitabine-based chemotherapy and duration of treatment were identified as significant risk factors associated with cardiotoxicity. The odds ratio were 15.7 (prior history of cardiac disease versus no history), 1.86 (capecitabine versus 5-FU), 1.06 (5–8 versus 1–4 chemotherapy cycles) and 1.58 (hypertension versus no hypertension), respectively. Conclusions Cardiotoxicity induced by fluoropyrimidines in the Chinese population may be underestimated in clinical practice. Close monitoring of patients is recommended, especially for those patients at high risk for cardiotoxicity. Possible risk factors are duration of treatment, capecitabine-based chemotherapy, pre-existing cardiac diseases and hypertension. Trial registration This study was initiated on January 22, 2014 and has been retrospectively registered with the registration number ChiCTR1800015434
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Affiliation(s)
- Jianjun Peng
- Center of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China
| | - Chao Dong
- Department of the Second Medical Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, 650118, Yunnan, P. R. China
| | - Chang Wang
- Department of Oncology, The First Hospital of Jilin University, Changchun, 130021, Jilin, P. R. China
| | - Weihua Li
- Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350014, Fujian, P. R. China
| | - Hao Yu
- Department of Biological Statistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, P. R. China
| | - Min Zhang
- Department of Cardiology, Shanghai Jiaotong University, Shanghai, 200030, P. R. China
| | - Qun Zhao
- The Third Surgery Department, the Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province, Shijiazhuang, 050011, Hebei, P. R. China
| | - Bo Zhu
- Institute of Cancer, Xinqiao Hospital of Third Military Medical University, Chongqing, 400037, P. R. China
| | - Jun Zhang
- Oncology Department, Shanghai Ruijin Hospital, Shanghai, 200025, P. R. China
| | - Wenliang Li
- Oncology Department, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, P. R. China
| | - Fenghua Wang
- Department of Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China
| | - Qiong Wu
- Medical Oncology, The first Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, P. R. China
| | - Wenhao Zhou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Donfeng Rd, East, Guangzhou, 510060, Guangdong, P. R. China
| | - Ying Yuan
- Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, P. R. China
| | - Meng Qiu
- Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan, P. R. China.
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Donfeng Rd, East, Guangzhou, 510060, Guangdong, P. R. China.
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Abstract
PURPOSE OF REVIEW The goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity. RECENT FINDINGS Most of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended. There is no recommendation regarding testing in adults. There is clear evidence pointing to the role of pharmacogenetics and pharmacogenomics in cardiotoxicity susceptibility to chemotherapeutic agents. Larger scale studies are needed to further identify susceptibility markers and to develop pharmacogenomics-based risk profiling to improve quality of life and life expectancy in cancer survivors.
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Affiliation(s)
- Vivian Y Chang
- Department of Pediatrics, Division of Hematology/Oncology, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
| | - Jessica J Wang
- Department of Medicine, Division of Cardiology, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
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Tuzovic M, Herrmann J, Iliescu C, Marmagkiolis K, Ziaeian B, Yang EH. Arterial Thrombosis in Patients with Cancer. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2018; 20:40. [PMID: 29627870 PMCID: PMC7658957 DOI: 10.1007/s11936-018-0635-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Cancer is a common cause of morbidity and mortality in the USA. While the association between venous thrombosis and malignancy is well established, arterial thrombosis has more recently been recognized as a serious complication of cancer and certain chemotherapeutic agents. This review aims to summarize the most recent literature regarding the incidence and risk factors for cancer-related arterial thrombosis, understand the pathophysiologic mechanisms of thrombosis, and highlight the specific diagnostic and treatment considerations relevant to cancer patients. RECENT FINDINGS Based on a recent study looking at the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of arterial thromboembolic events (ATEs) in patients with cancer at 6 months is 4.7%; the presence of an ATE is predictive of worse outcomes. Certain drugs such as platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors, and taxanes have been associated with high rates of ATEs. Increased platelet reactivity appears crucial to development of arterial thrombosis in cancer patients. Cancer patients have an increased risk of arterial thrombosis that is likely due to both a cancer-associated procoagulant state as well as the adverse effects of certain chemotherapeutic agents. Treatment of arterial thromboembolism in cancer patients typically requires a multidisciplinary approach in part due to high rates of thrombocytopenia and stent thrombosis in the setting of percutaneous interventions. More studies are needed to investigate optimal prophylaxis, surveillance strategies, and treatments of cancer-related arterial thromboembolic disease.
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Affiliation(s)
- Mirela Tuzovic
- UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, 100 Medical Plaza, Suite 630, Los Angeles, CA, 90095, USA
| | - Joerg Herrmann
- Division of Cardiovascular Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Cezar Iliescu
- Division of Cardiology, Department of Medicine, MD Anderson Cancer Center, University of Texas at Houston, Houston, TX, USA
| | | | - Boback Ziaeian
- UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, 100 Medical Plaza, Suite 630, Los Angeles, CA, 90095, USA
| | - Eric H Yang
- UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, 100 Medical Plaza, Suite 630, Los Angeles, CA, 90095, USA.
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Varricchi G, Ameri P, Cadeddu C, Ghigo A, Madonna R, Marone G, Mercurio V, Monte I, Novo G, Parrella P, Pirozzi F, Pecoraro A, Spallarossa P, Zito C, Mercuro G, Pagliaro P, Tocchetti CG. Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective. Front Physiol 2018; 9:167. [PMID: 29563880 PMCID: PMC5846016 DOI: 10.3389/fphys.2018.00167] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 02/20/2018] [Indexed: 12/28/2022] Open
Abstract
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis. Mitochondria are central targets for antineoplastic drug-induced CTX. Understanding the mechanisms of CTX is fundamental for effective cardioprotection, without compromising the efficacy of anticancer treatments. Type 1 CTX is associated with irreversible cardiac cell injury and is typically caused by anthracyclines and conventional chemotherapeutic agents. Type 2 CTX, associated with reversible myocardial dysfunction, is generally caused by biologicals and targeted drugs. Although oxidative/nitrosative reactions play a central role in CTX caused by different antineoplastic drugs, additional mechanisms involving directly and indirectly cardiomyocytes and inflammatory cells play a role in cardiovascular toxicities. Identification of cardiologic risk factors and an integrated approach using molecular, imaging, and clinical data may allow the selection of patients at risk of developing chemotherapy-related CTX. Although the last decade has witnessed intense research related to the molecular and biochemical mechanisms of CTX of antineoplastic drugs, experimental and clinical studies are urgently needed to balance safety and efficacy of novel cancer therapies.
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Affiliation(s)
- Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy
| | - Pietro Ameri
- Clinic of Cardiovascular Diseases, IRCCS San Martino IST, Genova, Italy
| | - Christian Cadeddu
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Alessandra Ghigo
- Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy
| | - Rosalinda Madonna
- Institute of Cardiology, Center of Excellence on Aging, Università degli Studi “G. d'Annunzio” Chieti – Pescara, Chieti, Italy
- Department of Internal Medicine, Texas Heart Institute and Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas Health Science Center, Houston, TX, United States
| | - Giancarlo Marone
- Section of Hygiene, Department of Public Health, University of Naples Federico II, Naples, Italy
- Monaldi Hospital Pharmacy, Naples, Italy
| | - Valentina Mercurio
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Ines Monte
- Department of General Surgery and Medical-Surgery Specialities, University of Catania, Catania, Italy
| | - Giuseppina Novo
- U.O.C. Magnetic Resonance Imaging, Fondazione Toscana G. Monasterio C.N.R., Pisa, Italy
| | - Paolo Parrella
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Flora Pirozzi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonio Pecoraro
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Paolo Spallarossa
- Clinic of Cardiovascular Diseases, IRCCS San Martino IST, Genova, Italy
| | - Concetta Zito
- Division of Clinical and Experimental Cardiology, Department of Medicine and Pharmacology, Policlinico “G. Martino” University of Messina, Messina, Italy
| | - Giuseppe Mercuro
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Carlo G. Tocchetti
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
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Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz-Flores S, Dent S, Kondapalli L, Ky B, Okwuosa T, Piña IL, Volgman AS. Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association. Circulation 2018; 137:e30-e66. [PMID: 29437116 PMCID: PMC6722327 DOI: 10.1161/cir.0000000000000556] [Citation(s) in RCA: 541] [Impact Index Per Article: 77.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet many people perceive breast cancer to be the number one threat to women's health. CVD and breast cancer have several overlapping risk factors, such as obesity and smoking. Additionally, current breast cancer treatments can have a negative impact on cardiovascular health (eg, left ventricular dysfunction, accelerated CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. For older women, CVD poses a greater mortality threat than breast cancer itself. This is the first scientific statement from the American Heart Association on CVD and breast cancer. This document will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy, and the prevention and treatment of CVD in breast cancer patients.
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Kenzik KM, Balentine C, Richman J, Kilgore M, Bhatia S, Williams GR. New-Onset Cardiovascular Morbidity in Older Adults With Stage I to III Colorectal Cancer. J Clin Oncol 2018; 36:609-616. [DOI: 10.1200/jco.2017.74.9739] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Purpose We sought to determine the long-term risk of cardiovascular disease (CVD)—stroke and myocardial infarction—and congestive heart failure (CHF) in older patients with colorectal cancer, as well as to understand the roles that preexisting comorbidities and cancer therapy play in increasing this risk. Patients and Methods We evaluated individuals from the SEER-Medicare database with incident stage I to III colorectal cancer at age older than 65 years between January 1, 2000, and December 31, 2011 (n = 72,408) and compared these patients with a matched cohort of Medicare patients without cancer (n = 72,408). Results Median age at diagnosis of colorectal cancer was 78 years (range, 66 years to 106 years), and median follow-up was 8 years since diagnosis. The 10-year cumulative incidence of new-onset CVD and CHF were 57.4% and 54.5% compared with 22% and 18% for control, respectively ( P < .001). The interaction between hypertension and chemotherapy was significant ( P < .001) for CVD, and that between diabetes and chemotherapy was significant ( P < .001) for CHF. Within the first 2 years since diagnosis, exposure to capecitabine alone increased CHF hazard (hazard ratio [HR], 3.6; 95% CI, 12.76 to 4.38) compared with exposure to fluorouracil alone. Conversely, patients who were treated with fluorouracil alone had a higher CVD hazard at < 2 years and > 2 years since diagnosis compared with patients who received capecitabine alone (< 2 years HR, 0.63; 95% CI, 0.53 to 0.75; > 2 years HR, 0.72; 95% CI, 0.62 to 0.84). Conclusion Older patients with colorectal cancer are at increased risk of developing CVD and CHF. Diabetes and hypertension interact with chemotherapy to increase the risk of cardiovascular morbidity. Future studies should assess the potential for personalized therapeutic options for those with preexisting morbidities and for structured monitoring for patients with a history of exposure to chemotherapy regimens, as well as explore the management of preexisting comorbidities to address long-term cardiovascular morbidity.
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Affiliation(s)
- Kelly M. Kenzik
- All authors: University of Alabama at Birmingham, Birmingham, AL
| | | | - Joshua Richman
- All authors: University of Alabama at Birmingham, Birmingham, AL
| | - Meredith Kilgore
- All authors: University of Alabama at Birmingham, Birmingham, AL
| | - Smita Bhatia
- All authors: University of Alabama at Birmingham, Birmingham, AL
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Ambesh P, Zivari K, Obiagwu C, Shetty V, Kamholz S, Hollander G, Shani J. Rapidly developing heart failure from capecitabine cardiotoxicity: a case study. Br J Clin Pharmacol 2018; 84:800-802. [PMID: 29336052 DOI: 10.1111/bcp.13509] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 12/24/2017] [Accepted: 01/05/2018] [Indexed: 12/21/2022] Open
Affiliation(s)
- Paurush Ambesh
- Department of Internal Medicine, Maimonides Medical Center, New York City, USA
| | - Kaveh Zivari
- Department of Internal Medicine, Maimonides Medical Center, New York City, USA
| | - Chukwudi Obiagwu
- Department of Cardiology, Maimonides Medical Center, New York City, USA
| | - Vijay Shetty
- Department of Cardiology, Maimonides Medical Center, New York City, USA
| | - Stephan Kamholz
- Department of Internal Medicine, Maimonides Medical Center, New York City, USA
| | - Gerald Hollander
- Department of Cardiology, Maimonides Medical Center, New York City, USA
| | - Jacob Shani
- Department of Internal Medicine, Maimonides Medical Center, New York City, USA
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Cioffi JH, Estes DJ, Florou V, Ardalan B. Treatment of advanced colorectal cancer in a patient with cardiotoxic reactions to 5-fluorouracil and capecitabine using suboptimal doses. BMJ Case Rep 2017; 2017:bcr-2017-220952. [PMID: 29183892 DOI: 10.1136/bcr-2017-220952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 32-year-old female with stage IV colorectal cancer and metastasis to the liver experienced cardiotoxic reactions after treatment with 5-fluorouracil and its oral prodrug capecitabine even at two-thirds the recommended dose. After careful considerations, the decision was made to attempt capecitabine retrial at a further suboptimal dose with combination chemotherapy where she no longer experienced cardiac events. As a result, the liver tumour shrank and rectal mass stabilised, tumour markers dropped and she underwent surgical resection of both masses. Later there was local recurrence of disease near the previous liver tumour, so the suboptimal capecitabine therapy was restarted without complaint. The patient became a candidate for a NanoKnife procedure, offering a potentially curative therapy. This case report summarises a novel treatment strategy for those patients with advanced colorectal cancer who experience cardiotoxic reactions to fluoropyrimidines, the active agent of gold standard treatment.
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Affiliation(s)
- Joseph H Cioffi
- School of Medicine, University of Miami, Miami, Florida, USA
| | - Derek J Estes
- Internal Medicine, Jackson Memorial Hospital, Miami, Florida, USA
| | - Vaia Florou
- Department of Haematology/Oncology, Internal Medicine, Jackson Memorial Hospital, Miami, Florida, USA
| | - Bach Ardalan
- Department of Haematology and Oncology, Internal Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida, USA
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Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. J Am Coll Cardiol 2017; 70:2536-2551. [PMID: 29145954 PMCID: PMC5825187 DOI: 10.1016/j.jacc.2017.09.1096] [Citation(s) in RCA: 260] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 09/24/2017] [Accepted: 09/26/2017] [Indexed: 12/27/2022]
Abstract
Modern cancer therapy has successfully cured many cancers and converted a terminal illness into a chronic disease. Because cancer patients often have coexisting heart diseases, expert advice from cardiologists will improve clinical outcome. In addition, cancer therapy can also cause myocardial damage, induce endothelial dysfunction, and alter cardiac conduction. Thus, it is important for practicing cardiologists to be knowledgeable about the diagnosis, prevention, and management of the cardiovascular complications of cancer therapy. In this first part of a 2-part review, we will review cancer therapy-induced cardiomyopathy and ischemia. This review is based on a MEDLINE search of published data, published clinical guidelines, and best practices in major cancer centers. With the number of cancer survivors expanding quickly, the time has come for cardiologists to work closely with cancer specialists to prevent and treat cancer therapy-induced cardiovascular complications.
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Affiliation(s)
- Hui-Ming Chang
- Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, Missouri
| | - Rohit Moudgil
- Department of Cardiology, University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Tiziano Scarabelli
- Division of Cardiology, Virginia Common Wealth University, Richmond, Virginia
| | - Tochukwu M Okwuosa
- Division of Cardiology, Rush University Medical Center, Chicago, Illinois
| | - Edward T H Yeh
- Center for Precision Medicine, Department of Medicine, University of Missouri, Columbia, Missouri.
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Klee NS, McCarthy CG, Martinez-Quinones P, Webb RC. Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy. Ther Adv Cardiovasc Dis 2017; 11:297-317. [PMID: 28911261 PMCID: PMC5933669 DOI: 10.1177/1753944717729141] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 08/09/2017] [Indexed: 12/18/2022] Open
Abstract
Cardio-oncology is a new and rapidly expanding field that merges cancer and cardiovascular disease. Cardiovascular disease is an omnipresent side effect of cancer therapy; in fact, it is the second leading cause of death in cancer survivors after recurrent cancer. It has been well documented that many cancer chemotherapeutic agents cause cardiovascular toxicity. Nonetheless, the underlying cause of cancer therapy-induced cardiovascular toxicity is largely unknown. In this review, we discuss the potential role of damage-associated molecular patterns (DAMPs) as an underlying contributor to cancer therapy-induced cardiovascular toxicity. With an increasing number of cancer patients, as well as extended life expectancy, understanding the mechanisms underlying cancer therapy-induced cardiovascular disease is of the utmost importance to ensure that cancer is the only disease burden that cancer survivors have to endure.
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Affiliation(s)
- Nicole S. Klee
- Department of Physiology, Medical College of Georgia at Augusta University, 1120 15 Street, Augusta, GA 30912, USA
| | - Cameron G. McCarthy
- Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Patricia Martinez-Quinones
- Departments of Physiology and Surgery, Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - R. Clinton Webb
- Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA
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Layoun ME, Wickramasinghe CD, Peralta MV, Yang EH. Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management. Curr Oncol Rep 2017; 18:35. [PMID: 27113369 DOI: 10.1007/s11912-016-0521-1] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Fluoropyrimidines-5-fluorouracil (5-FU) and capecitabine-have been implicated as cardiotoxic chemotherapy agents. This rare, albeit potentially serious toxicity has been described in nearly four decades of case reports, case series, and in vitro modeling; however, there is a paucity in clinical trials and prospective analyses focused on cardioprotective strategies and cardiotoxic surveillance of these agents. While much attention has focused on the well-known cardiac toxicity of anthracyclines and monoclonal antibody agents such as trastuzumab, fluoropyrimidines remain one of the most common causes of chemotherapy-associated cardiotoxicity. The introduction of capecitabine, an oral prodrug of 5-FU, has made the treatment of solid tumors more convenient along with a subsequent rise in documented cardiotoxic cases. This review discusses the symptomatology, clinical manifestations, and proposed molecular mechanisms that attempt to describe the heterogeneous spectrum of fluoropyrimidine-induced cardiotoxicity. Four case examples showcasing the varied manifestations of cardiotoxicity are presented. Finally, several proposed management strategies for cardiotoxicity and post-hospital course precautions are discussed.
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Affiliation(s)
- Michael E Layoun
- Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA
| | - Chanaka D Wickramasinghe
- Division of Cardiology, Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA
| | - Maria V Peralta
- Division of Internal Medicine, Department of Medicine, Beaumont Hospital-Dearborn, Dearborn, MI, USA
| | - Eric H Yang
- Division of Cardiology, Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA.
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Report of two cases of acute cardiac adverse events in patients with colorectal carcinoma receiving oral capecitabine. Anticancer Drugs 2017; 28:801-807. [DOI: 10.1097/cad.0000000000000509] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Kwakman JJ, Simkens LH, Mol L, Kok WE, Koopman M, Punt CJ. Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group. Eur J Cancer 2017; 76:93-99. [DOI: 10.1016/j.ejca.2017.02.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 01/26/2017] [Accepted: 02/07/2017] [Indexed: 12/27/2022]
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Giza DE, Boccalandro F, Lopez-Mattei J, Iliescu G, Karimzad K, Kim P, Iliescu C. Ischemic Heart Disease: Special Considerations in Cardio-Oncology. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2017; 19:37. [PMID: 28425056 DOI: 10.1007/s11936-017-0535-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
OPINION STATEMENT The interplay and balance between the competing morbidity and mortality of cardiovascular diseases and cancer have a significant impact on both short- and long-term health outcomes of patients who survived cancer or are being treated for cancer. Ischemic heart disease in patients with cancer or caused by cancer therapy is a clinical problem of emerging importance. Prompt recognition and optimum management of ischemic heart disease mean that patients with cancer can successfully receive therapies to treat their malignancy and reduce morbidity and mortality due to cardiovascular disease. In this sense, the presence of cancer and cancer-related comorbidities (e.g., thrombocytopenia, propensity to bleed, thrombotic status) substantially complicates the management of cardiovascular diseases in cancer patients. In this review, we will summarize the current state of knowledge on the management strategies for ischemic disease in patients with cancer, focusing on the challenges encountered when addressing these complexities.
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Affiliation(s)
- Dana Elena Giza
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Fernando Boccalandro
- Odessa Heart Institute,Department of Internal Medicine, Permian Research Foundation, Texas-Tech University, Odessa, TX, 79761, USA
| | - Juan Lopez-Mattei
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Gloria Iliescu
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Kaveh Karimzad
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Peter Kim
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA
| | - Cezar Iliescu
- The Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
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