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      • Record: found
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      5-fluorouracil and cardiotoxicity: a review

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          Abstract

          Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.

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          Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

          J Suwaidi, S Hamasaki, S T Higano … (2000)
          Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.
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            Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses.

            Greg Yothers, C Allegra, David J. O’Connell … (2011)
            The National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial demonstrated that the addition of oxaliplatin to fluorouracil plus leucovorin (FULV) improved disease-free survival (DFS) in patients with stage II or III colon cancer. This analysis is the first publication of overall survival (OS) for the NSABP C-07 study. We updated DFS and examined both end points in clinically relevant patient subsets. Other studies have identified patients age 70 or older and those with stage II disease as patient subsets in which oxaliplatin may not be effective. We investigated toxicity as a driver of divergent outcomes in these subsets. In all, 2,409 eligible patients with follow-up were randomly assigned to either FULV (FU 500 mg/m(2) by intravenous [IV] bolus weekly for 6 weeks; leucovorin 500 mg/m(2) IV weekly for 6 weeks of each 8-week cycle for three cycles) or FLOX (FULV plus oxaliplatin 85 mg/m(2) IV on days 1, 15, and 29 of each cycle). With 8 years median follow-up, OS was similar between treatment groups (hazard ratio [HR], 0.88; 95% CI, 0.75 to 1.02; P = .08). FLOX remained superior for DFS (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002). The effect of oxaliplatin on OS did not differ by stage of disease (interaction P = .38 for OS; interaction P = 0.37 for DFS) but did vary by age for OS (younger than age 70 v 70+ interaction P = .039). There was a similar trend for DFS (interaction P = .073). Oxaliplatin significantly improved OS in patients younger than age 70 (HR, 0.80; 95% CI, 0.68 to 0.95; P = .013), but no positive effect was evident in older patients. Overall, the addition of oxaliplatin to FULV has not been proven to extend OS in this trial, but the DFS effect remained strong. Unplanned subset analyses suggest a significant OS effect of oxaliplatin in patients younger than age 70.
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              Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.

              M Kuperminc, Aimee Wong, Scott C. Weaver … (2001)
              To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.
              Article 0 comments Cited 151 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jaskanwal D. Sara
                Jasvinder Kaur
                Ryan Khodadadi
                Muneeb Rehman
                Ronstan Lobo
                Sakti Chakrabarti
                Joerg Herrmann
                Amir Lerman
                Axel Grothey
                Journal
                Journal ID (nlm-ta): Ther Adv Med Oncol
                Journal ID (iso-abbrev): Ther Adv Med Oncol
                Journal ID (publisher-id): TAM
                Journal ID (hwp): sptam
                Title: Therapeutic Advances in Medical Oncology
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 1758-8340
                ISSN (Electronic): 1758-8359
                Publication date (Electronic): 18 June 2018
                Publication date Collection: 2018
                Volume: 10
                Electronic Location Identifier: 1758835918780140
                Affiliations
                [1-1758835918780140]Department of Cardiovascular Diseases, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905-0001, USA
                [2-1758835918780140]Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Maidstone, Kent, UK
                [3-1758835918780140]Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
                [4-1758835918780140]Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
                [5-1758835918780140]Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
                [6-1758835918780140]Department of Medical Oncology, Mayo College of Medicine, Rochester, MN, USA
                [7-1758835918780140]Department of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA
                [8-1758835918780140]Department of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA
                [9-1758835918780140]Department of Medical Oncology, Mayo College of Medicine, Rochester, MN, USA
                Author notes
                Article
                Publisher ID: 10.1177_1758835918780140
                DOI: 10.1177/1758835918780140
                PMC ID: 6024329
                PubMed ID: 29977352
                SO-VID: 07acd889-d913-4050-b822-fcafcb7870dd
                Copyright © © The Author(s), 2018
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 12 February 2018
                Date accepted : 25 April 2018
                Categories
                Subject: Review
                Custom metadata
                cover-date January-December 2018

                Keywords: 5-fluorouracil,cardiotoxicity,chemotherapy,coronary vasospasm,fluoropyrimidine
                Data availability:
                Keywords: 5-fluorouracil, cardiotoxicity, chemotherapy, coronary vasospasm, fluoropyrimidine

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