br Keywords FU Arrhythmias Colon cancer Ischemia Rectal
Keywords: 5FU, Arrhythmias, Colon cancer, Ischemia, Rectal cancer
5-Fluorouracil (5-FU) represents the backbone of systemic therapy regimens of colorectal cancer (CRC), both in the adjuvant and metastatic settings.1 In addition to the common toxicities of 5-FU (like diarrhea and AWD 131-138 toxicities), cardiac toxicity stands out as
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, Canada
Address for correspondence: Dr Omar Abdel-Rahman, MD, Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, T2N4N1 Canada E-mail contact: [email protected]
a serious, albeit uncommon, side effect of 5-FU-based chemo-therapy.2 The most notorious cardiac toxicities associated with 5-FU include coronary vasospasm, coronary thrombosis, and sud-den cardiac death.3
Previous studies evaluating the patterns of 5-FU-related cardiotoxicity were mostly based on retrospective institution- or population-based registries.4 Moreover, the cardiotoxicity of newer 5-FU-based regimens combining targeted therapies with chemo-therapy was not adequately assessed.5 Additionally, in many of these studies, the baseline cardiac status of included patients is not clear.6
Thus, there is a need to thoroughly assess the patterns of cardiac events among 5-FU-treated patients based on credible prospectively collected datasets that incorporate chemotherapy/targeted therapy combinations. It is also important to ensure that the baseline cardiac
Table 1 Cohorts Included in the Pooled Analysis
Patients in the
Study Treatment Regimen Pooled Analysis, % Start Date Completion Date
Active comparator: chemotherapy and bevacizumab.
Active comparator: FOLFOX alone
(comparator arm only)a
Abbreviations: FOLFOX ¼ 5-FU, leucovorin, and oxaliplatin; PACCE ¼ Panitumumab Advanced Colorectal Cancer Evaluation Study; PRIME ¼ Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy. aIn these 3 studies, only comparator arms were included.
status of included patients is well-known. The best vignette to fulfill the above requirements is a secondary analysis of clinical trial datasets.
Project Data Sphere (PDS) represents an important initiative from a number of stakeholders who are interested in sharing of de-identified clinical trial datasets.7 Within vernalization portal, a number of clinical trials evaluating different 5-FU-based regimens in the first-line treatment of metastatic CRC are present. A secondary anal-ysis of these clinical trials was deemed a credible way to answer the above research question.
Given the position of CRC as one of the most common cancers as well as one of the leading causes of cancer mortality worldwide, and given the widespread use of 5-FU-based regimens in both adjuvant and metastatic settings of this disease, results of the current analysis should hopefully inform practicing physicians and help patients.8,9
The aim of the current study is to evaluate the patterns and predictors of cardiac adverse events associated with various 5-FU-based systemic therapy regimens among patients with metastatic CRC.
Materials and Methods
The primary data sources for the current study include de-identified datasets from 5 randomized studies (NCT00272051, NCT00305188, NCT00115765, NCT00364013, and NCT00384176). These studies evaluated different systemic therapy regimens in the setting of first-line treatment of metastatic CRC. These de-identified datasets were obtained from the PDS platform after having relevant approvals. Informed consent was obtained from all included participants in all included studies. Primary methodological considerations and eligibility criteria were detailed in the clinicaltrials.gov records of each study. Primary results were published elsewhere for the following 3 trials: NCT00115765, NCT00364013, and NCT00384176.10-12