Fluoropyrimidine-induced Cardiotoxicity Research Articles

A novel outpatient regimen in management of fluoropyrimidine-induced cardiotoxicity.

Fluoropyrimidines (FP) are cornerstone drugs in the treatment of gastrointestinal (GI) malignancies. Cardiotoxicity secondary to an FP chemotherapy is a serious complication. There are no standardized guidelines on the treatment of FP induced cardiotoxicity which may result in interruption and even discontinuation of life saving treatment. We present our experience in FP rechallenge using a novel outpatient regimen based on our "up-front" triple agent antianginal protocol. We report the retrospective study of the patients with suspected FP induced cardiotoxicity. Patients meeting the criteria were selected by C3OD (curated cancer clinical outcomes database) at Kansas University Medical Center (KUMC). We identified all patients with gastrointestinal malignancies who had suspected FP induced cardiotoxicity from January 2015 to March 2022. We then included the patients who were rechallenged with planned fluoropyrimidine regimen utilizing the three drug KU-protocol. We utilized a novel regimen by repurposing the already FDA-approved anti-anginal drugs in a manner that minimizes the risk of hypotension and bradycardia. In this retrospective study, 10 patients with suspected fluoropyrimidine induced cardiotoxicity were included from January-2015 to March-2022 at KUMC. Out of 10 patients who were rechallenged utilizing KU-protocol, eight patients (80%) were able to complete the previously planned fluoropyrimidine regimen. None of the patients required ER visits or hospital admission due to cardiac symptoms during the rechallenge utilizing the KU-protocol. Utilizing our novel outpatient regimen, we have successfully and safely allowed re-challenge of FP chemotherapy with good tolerability and completion of the intended course of chemotherapy without recurrent morbidity.

Risk factors for fluoropyrimidine-induced cardiotoxicity in colorectal cancer: A retrospective cohort study and establishment of a prediction nomogram for 5-FU induced cardiotoxicity.

Fluoropyrimidine is an important component of systemic chemotherapy for colorectal cancer (CRC). Fluoropyrimidine-induced cardiotoxicity (FIC) may result in delay and discontinuation of chemotherapy and, in severe cases, can even be life-threatening. To date, risk factors for FIC have not been well identified. This cohort study aimed to identify the predictors of FIC in CRC patients and develop a risk prediction nomogram model. Between January 1, 2018 and December 31, 2020, colorectal cancer patients who received 5-fluoropyrimidine(5-Fu)/capecitabine-based chemotherapy in Affiliated Cancer Hospital of Guizhou Medical University were included. FIC was defined as an adverse cardiovascular event related to fluoropyrimidine that occurred during or within four weeks of completing chemotherapy. Risk factors were determined by LASSO algorithm and multivariate logistic regression analysis. Nomogram for predicting 5-Fu-induced cardiotoxicity was established and internally validated. The concordance index (C-index) and calibration curve were used to evaluate the nomogram's discrimination and accuracy. A total of 916 patients were included for analysis, and 200 [21.8%,95% confidence interval (CI):19.12%-24.47%] experienced FIC. LASSO algorithm and multivariate logistic regression analysis determined that chemotherapy ≤3 cycles (OR=4.694, 95%CI=3.184-6.92), age≥ 60 (OR=1.678, 95%CI=1.143-2.464), BMI>22.97 (OR=1.77, 95%CI=1.202-2.606), and simultaneous use of bevacizumab (OR=2.922, 95%CI=1.835-4.653) were significant risk factors, and were included in the prediction model for 5-Fu induced cardiotoxicity. The C-index (95%CI) was 0.751 (0.706-0.795) by internal validation. For patients treated with capecitabine-based regimen, the incidence of FIC increased with the absolute value of neutrophils (OR=5.177, 95%CI=1.684-15.549) and eosinophils (OR=3.377,95% CI=1.237-9.22). Our study identified risk factors for FIC and established a prediction nomogram model based on chemotherapy cycle, age, BMI and use of target therapy for 5-FU induced Cardiotoxicity. The discriminative prediction model can be used for patient counselling and risk-stratification before undergoing chemotherapy in colorectal cancer.

Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management.

Cancer is a growing public health problem; it is responsible annually for millions of deaths worldwide. Fluoropyrimidines are highly effective and commonly prescribed anti-neoplastic drugs used in a wide range of chemotherapy regimens against several types of malignancies. 5-fluorouracil and its prodrugs affect neoplastic cells in multiple ways by impairing their proliferation, principally through the inhibition of thymidylate synthase. Fluoropyrimidine-induced cardiotoxicity was described more than 50 years ago, but many details such as incidence, mechanisms, and treatment are unclear and remain disputed. Severe cardiotoxicity is not only life-threatening, but also leads to withdrawal from an optimal chemotherapy regimen and decreases survival rate. Differences in the frequency of cardiotoxicity are explained by different chemotherapy schedules, doses, criteria, and populations. Proposed pathophysiological mechanisms include coronary vasospasm, endothelial damage, oxidative stress, Krebs cycle disturbances, and toxic metabolites. Such varied pathophysiology of the cardiotoxicity phenomenon makes prevention and treatment more difficult. Cardiovascular disturbances, including chest pain, arrhythmias, and myocardial infarction, are among the most common side effects of this class of anti-neoplastic medication. This study aims to summarize the available data on fluoropyrimidine cardiotoxicity with respect to symptoms, incidence, metabolism, pathophysiological mechanism, diagnosis, management, and resistance.

A novel outpatient regimen in management of fluoropyrimidine-induced cardiotoxicity.

e15613 Background: Fluoropyrimidines, such as 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapies for solid tumors, and essential for curative intent treatment of colorectal cancer. But sometimes, their use may be limited by cardiac toxicity limiting the possibility of cure in some patients. Cardiotoxicity could be asymptomatic (EKG changes) or manifested as chest pain, arrhythmias, acute coronary syndrome or death. Rechallenging may be daunting and it may result in interruption or even discontinuation of planned chemo. Traditionally, nitrates and/or IV/oral calcium channel blockers (CCB) have been used for management of fluoropyrimidine-induced cardiotoxicity but without much benefit. Ranolazine, an oral antianginal drug approved for chronic angina, diminishes myocardial ischemia by reducing calcium overload caused by inhibition of late sodium current and it does not affect heart rate or blood pressure. Our objective was to evaluate the efficacy of our novel approach using ranolazine with other traditional drugs. Methods: 8 patients (median age 49.5 yrs) with fluoropyrimidine induced cardiotoxicity were retrospectively analyzed. They were rechallenged with the planned fluoropyrimidine regimen with our 3 drug cardioprotective regimen (KU protocol). This included oral Ranolazine 1000mg BID and Amlodipine 2.5 mg daily to start the day before starting 5FU infusion/oral capecitabine and to continue it until the day after completion of infusion/treatment, and Nitroglycerin paste 1 inch every 6 hours starting before infusion and continue until it was completed. These meds were discontinued upon completion of chemo. Results: 8 patients were rechallenged with fluoropyrimidine utilizing KU protocol, 6 patients (75%) were able to complete previously planned fluoropyrimidine regimen. One pt (*) discontinued capecitabine due to recurrent chest pain and treatment was switched to 5FU based regimen with KU protocol, which pt was able to complete without chest pain. Another pt (**), 5FU was stopped due to severe diarrhea, not due to cardiotoxicity. All pts tolerated KU protocol well. Conclusions: In our small, single center experience, we were able to safely and effectively rechallenge pts with fluoropyrimidines and complete curative intent treatment with our KU protocol. This protocol uses FDA approved oral and transcutaneous drugs without requiring a healthcare personnel to administer an IV CCB that can cause precipitous bradycardia and/or hypotension. Our results need validation in a larger cohort. [Table: see text]

Fluoropyrimidine-induced cardiotoxicity.

Cardio-oncology is a discipline based on early screening, monitoring, and treating chemotherapy-induced cardiotoxicity. There are many chemotherapeutics known for their cardiac toxic effects, including fluoropyrimidines. Fluoropyrimidine represents the cornerstone of many types of cancer and each year almost two million cancer patients undergo this treatment. Fluoropyrimidine-induced cardiotoxicity can be manifested in several forms, from angina pectoris to sudden death. This paper is a review of how the cardiotoxicity of fluoropyrimidines is presented, the mechanisms of its occurrence, its diagnosis, and management.

Abstract 15723: Risk Factors of Fluoropyrimidine Induced Cardiotoxicity Among Cancer Patients: A Systematic Review and Meta-analysis

Introduction: Cancer patients are at increased risk of experiencing cardiotoxicity during their fluoropyrimidine-based chemotherapy. However, risk factors for fluoropyrimidine-induced cardiotoxicity (FIC) are not entirely understood. Methods: We searched PubMed, PsycINFO, IPA, CINAHL, Web of Science and ClinicalTrials.gov for studies published between January 1, 1990 and December 31, 2019, examining risk factors for cardiotoxicity induced by 5-fluorouracil, capecitabine or floxuridine. Two reviewers independently assessed publication quality and extracted study-level data into standardized evidence tables. Review Manager 5 software was used to convert data to risk ratios (RRs) and calculate pooled RRs for meta-analyses using a random-effects method. We conducted a Cochran’s Q test and obtained I 2 index to quantify study heterogeneity in each meta-analysis, with prediction interval (PI) to show the expected range of true effects in future similar studies. Results: Of 690 publications identified for abstract and title screening, 22 unique studies were included in the final review, and 20 of them had sufficient data for meta-analyses. Results indicated that patients undergoing capecitabine-based combination therapy had a higher risk of FIC than those with capecitabine monotherapy (pooled RR=1.61, 95% CI=1.01-2.55, I 2 =0%, 95% PI=0.08-31.71). Also, patients with pre-existing cardiac disease (pooled RR=3.01, 95% CI=2.02-4.49, I 2 =42%, 95% PI=1.03-8.78), hypertension (pooled RR=1.52, 95% CI=1.20-1.93, I 2 =0%, 95% PI=1.08-2.13) or smoking habit (pooled RR=2.22, 95% CI=1.03-4.78, I 2 =39%, 95% PI=0.15-32.46) had a significantly higher risk of FIC than their counterparts, while gender and comorbidities including diabetes, hyperlipidemia, and obesity were not significant risk factors of FIC. Conclusions: Cancer patients with pre-existing cardiac disease, hypertension, and smoking behavior had a higher risk of FIC when they are undergoing fluoropyrimidine-based treatments. Further research is needed to develop risk assessment tools for a risk prediction of FIC among cancer patients, which could advance risk stratification strategies and improve patient outcomes during the application of fluoropyrimidine-based treatments.

Alternative Treatment Options in Patients with Colorectal Cancer Who Encounter Fluoropyrimidine-Induced Cardiotoxicity.

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.

Safety and Efficacy of s-MOX Regimen in Patients with Colorectal Cancer Who Developed Cardiotoxicity Following Fluoropyrimidine Administration: A Case Series

Fluoropyrimidines compose the backbone of regimens to treat many common solid tumors, including gastrointestinal (GI), breast and head/neck. As we continue to use these agents routinely, recognition of rare but real toxicities, such as cardiotoxicity, has also improved. The treatment options for patients who have encountered fluoropyrimidine-induced cardiotoxicity are limited as many anti-angiogenic drugs also pose a cardiac risk. We present a case series of three patients who developed cardiotoxicity in the form of anginal-like symptoms, EKG changes and elevated cardiac enzymes on infusional 5-FU or capecitabine and were subsequently treated with the s-MOX (simplified-mitomycin-oxaliplatin) regimen for their metastatic colorectal cancer (mCRC). All three patients were tested for polymorphic abnormality of DYPD and TYMS. All three patients were treated with s-MOX consisting of mitomycin-C 7 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on days 1 and 15 (1 cycle = 28 days) after they encountered cardiotoxicity to 5-FU and/or capecitabine. None of these patients developed any cardiotoxicity on s-MOX. Overall, the MOX regimen was well tolerated. The most common toxicities included ≤ 2 grade peripheral neuropathy, nausea, vomiting, thrombocytopenia, and anemia. Grade ≥ 3 toxicities included neutropenia (10%), thrombocytopenia (33%), vomiting (8%), and peripheral neuropathy (30%). DYPD gene was normal in all patients and TYMS was abnormal (2R/2R) in one patient. This is the first case series that reports the safety and feasibility of s-MOX in patients with mCRC who developed cardiac toxicity to 5-FU or capecitabine. The s-MOX regimen may provide an alternative treatment option for patients who either develop fluoropyrimidine-related cardiotoxicity or who have abnormalities in the DYPD gene.

589P - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: Preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)

BackgroundFluoropyrimidines (FP) are the backbone chemotherapy (CT) for colorectal cancer (CRC). Although the most common toxicities have been extensively studied, FP-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity, still lacks of a comprehensive characterization. The correlation between FIC and known cardiovascular (CV) risk factors remains controversial and based on retrospective observations. MethodsCRC patients (pts) treated for the first time with FP at Candiolo Cancer Institute have been enrolled since January 2016. All pts were screened for potential CV risk factors; if needed, the treatment of preexisting CV comorbidities was optimized before starting CT. During the first 3 CT cycles, a monitoring with CV symptoms collection, seriated electrocardiograms and brain natriuretic peptide (BNP) measurements was performed. Primary objective was to assess the incidence of FIC. Secondary objectives included the analysis of the relationship of FIC with known CV risk factors and BNP levels. ResultsAn interim analysis was conducted on 101 pts (65% male, median age 71.6 years). We found high prevalence of CV risk factors (BMI ≥25 54.2%, smoker 50%, heavy drinker 23%, sedentary lifestyle 63.3%) and comorbidities (diabetes mellitus 19.2%, dyslipidemia 34.7%, arterial hypertension 54%, stroke 3%, coronary artery disease 6%, arrhythmias 8%, heart failure 4%). 19 pts (18.8%) experienced FIC: 1 acute coronary syndrome (ACS), 1 coronary vasospasm, 1 paroxysmal supraventricular tachycardia (PSVT), 1 complete left bundle branch block (LBBB), 2 syncope, 4 typical chest pain, 6 sudden dyspnea, 3 sudden palpitations. After treatment of the CV events, only 3 pts had to discontinue FP (ACS, LBBB and PSTV). Among symptomatic pts, only 47% had CV comorbidities and/or CV risk factors. BNP levels increased on average by 73% [CI 99%: +39% - +106%] after the first cycle. ConclusionsA high incidence of CV events, with no apparent correlation with CV comorbidities or risk factors, was observed. Prompt identification and treatment of CV events allowed most pts to complete the treatment with FP. Clinical trial identificationNCT02665312. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM. Aglietta: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

Fluoropyrimidine-induced cardiotoxicity.

Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs, widely used for the treatment of a variety of cancers, both in adjuvant and in metastatic setting. Although the most common toxicities of these drugs have been extensively studied, robust data and comprehensive characterization still lack concerning fluoropyrimidine-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity. This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, uridine triacetate. The role of alternative chemotherapeutic options, namely raltitrexed and TAS-102, is discussed, and, lastly, we overview the most promising future directions in the research on FIC and development of diagnostic tools, including microRNA technology.

Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management.

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.

Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed

Introduction: 5-fluorouracil continues to be the cornerstone of treatment for colorectal cancer. Although fluoropyrimidines are generally considered as well-tolerated drugs, severe toxicities can be a major clinical problem, and the recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients. Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of administration.Areas covered: In this review, through critical insight into the mechanism of action and main clinical experiences, the authors suggest the necessity to reconsider raltitrexed as a valuable anticancer drug and as a suitable option for colorectal cancer. The authors highlight its emerging therapeutic role in clinical practice for patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.Expert opinion: This review discusses if TS could still be a relevant target for colorectal cancer in the era of molecular therapy and if raltitrexed should still be considered a drug with a life-threatening toxicity. Furthermore, this review discusses the principal combination clinical experiences of raltitrexed and its emerging therapeutic role in clinical practice as a suitable option for colorectal cancer patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.

Use of raltitrexed as an alternative to 5-fluorouracil and capecitabine in cancer patients with cardiac history

AimFluoropyrimidines are the backbone of the majority of approved chemotherapy regimens for colorectal cancer (CRC). However, there are reports of fluoropyrimidine treatments being associated with cardiotoxicity which have led to permanent cardiovascular damage and even death. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-fluorouracil (5-FU) is not tolerated or inappropriate. A systematic review was undertaken to determine the incidence of cardiotoxicity associated with 5-FU, capecitabine and raltitrexed. MethodsAn electronic search of PubMed was undertaken to identify articles relating to cardiotoxicity associated with 5-FU, capecitabine or raltitrexed, published between January 1991 and August 2011. Additionally, a retrospective review of cardiotoxicity associated with raltitrexed at our treatment centres was conducted. ResultsTwenty studies were examined. The overall incidence of cardiotoxicity associated with 5-FU/capecitabine varied between 0.55% and 19% (mean: 5.0%, median: 3.85%). No published data were identified reporting cardiotoxicity associated with raltitrexed. A retrospective review at our treatment centres revealed that the incidence was 4.5% amongst high-risk patients treated with raltitrexed (n=111) for advanced gastrointestinal cancer with a significant cardiac history and/or previous cardiotoxicity with 5-FU or capecitabine. ConclusionThe incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC treated is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with other fluoropyrimidines or were unable to tolerate capecitabine due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or significant cardiovascular risk factors.

P-0255 Use of Raltitrexed as an Alternative to 5-Fu and Capecitabine in Cancer Patients with Cardiac History

ABSTRACT Introduction Fluoropyrimidines are the backbone of the majority of approved chemotherapy regimens for colorectal cancer (CRC). However, there are reports of fluoropyrimidine treatments being associated with cardiotoxicity which have led to permanent cardiovascular damage and even death. A review of 20 studies suggests an overall mean incidence of 5-fluorouracil (5-FU) associated cardiotoxicity of 4.99%. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-FU is not tolerated or inappropriate. This study aimed to determine the incidence of raltitrexed-associated cardiotoxicity at our treatment centres. Methods We conducted a retrospective review of 111 patients treated with raltitrexed for primary gastrointestinal tumours at two UK treatment centres. The time period for inclusion was January 2008–January 2011 inclusive at the Christie Hospital, Manchester, UK, and April 2006–March 2011 inclusive at Mount Vernon Cancer Centre, Middlesex, UK. This consisted of a pharmacy database search for patients having received raltitrexed. Electronic patient records and patient notes were accessed for each patient and the following data were collected: treatment intent, reason for raltitrexed administration (first-line due to cardiac comorbidity or following 5-FU complications), number of cycles of raltitrexed received, complications whilst on raltitrexed treatment, and patient outcome. Results A total of 111 patients with advanced CRC treated with raltitrexed in two treatment centres were included in the retrospective review. Patients were aged 33–85 years (median age: 68 years) and 74% were male (male: n=82; female: n=29). In this audit, 41.4% (n=46) of patients received first-line raltitrexed treatment whilst 58.5% (n=65) of patients switched to raltitrexed from another regimen; 96.9% (n=63) of these patients receiving second-line raltitrexed therapy switched following cardiovascular complications associated with capecitabine. Of the patients receiving first-line raltitrexed therapy, 89% had a history of ischaemic heart disease and 4.3% had a history of cerebrovascular accident or transient ischaemic attack. The reasons for receiving first-line raltitrexed therapy were not documented in three patients. The study revealed that five of the 111 patients had confirmed cardiac complications whilst receiving raltitrexed therapy, equating to an incidence of 4.5%. This is in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with capecitabine (n=3) or were considered unable to tolerate capecitabine due to their previous cardiac history (n=2) and hence represents a favourable result. Of these, two patients experienced acute coronary syndrome, one suffered from myocardial infarction, one had chest pain and one suffered from a stroke. Conclusion The incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with fluoropyrimidines or were unable to tolerate fluoropyrimidines due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or with significant cardiovascular risk factors.

613 POSTER Randomized phase III trial in locally advanced rectal cancer: preoperative chemoradiotherapy with oral uracil and tegafur/leucovorin versus intravenous fluorouracil/leucovorin

Most chemotherapy regimens in colorectal cancer treatment are 5-fluorouracil (5-FU)/leucovorin or capecitabine-based. Cardiotoxicity is a less common but potentially lethal complication of 5-FU or capecitabine treatment, and some physicians might be unfamiliar with treatment alternatives. Rechallenging should be avoided because it carries a high risk of recurrence of the cardiac symptoms and prophylactic treatment is not always protective. Possible alternative treatment options to be considered are to replace the oral capecitabine or intravenous 5-FU by a 5-FU bolus regimen, by uracil-tegafur or tegafur/gimeracil/oteracil, both oral fluoropyrimidines combining a 5-FU prodrug with a dihydropyrimidine dehydrogenase (DPD) inhibitor, or by raltitrexed, a thymidilate synthase inhibitor whose metabolism is independent of DPD. Patients with advanced colorectal cancer and fluoropyrimidine-induced cardiotoxicity can be treated with other non-fluoropyrimidine related chemotherapy, either as a single agent, combined, or in combination with biological agents. In this report we discuss the different alternative treatment options.

Cardiotoxicity and Capecitabine: A Case Report

Oral fluoropyrimidines increasingly are being developed and studied as a novel treatment for breast, colorectal, and other cancers. Fluoropyrimidines are designed to generate 5-fluorouracil (5-FU) preferentially within tumors. Cardiotoxicity is a rare complication associated with 5-FU and oral fluoropyrimidine treatments. Chest pain is the most common presenting symptom, and, in many cases, the cardiotoxicity is partly or completely reversible. This article reviews fluoropyrimidine-induced cardiotoxicity and presents a case report of a woman who experienced this complication during capecitabine treatment.