Fluoropyrimidine-induced hand-foot syndrome and cardiotoxicity: recommendations for the use of the oral fluoropyrimidine S-1 in metastatic colorectal cancer

Punt, Cornelis J.A.; Maughan, T; Cremolini, Chiara; Cutsem, Éric Van; McDermott, Ray; Bodoky, G; André, Thierry; Österlund, Pia; Teske, Arco J.; Pfeiffer, Per

doi:10.1016/j.esmoop.2023.101199

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…However, rechallenge with CAP or infused 5-FU puts the patient at high risk of cardiotoxicity recurrence and even mortality [3,43]. The effect of dose reduction with or without prophylactic cardioprotective drugs is modest at best [5,44,45]. Three case series of 5, 6, and 10 patients found that bolus 5-FU is feasible after previous cardiotoxicity on infused/oral FP with recurrence of cardiotoxicity in 0%-20% [13,46,47].…”

Section: Discussionmentioning

confidence: 99%

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

Kinos,

Hagman,

Halonen

et al. 2024

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Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

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Section: Discussionmentioning

confidence: 99%

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

Kinos,

Hagman,

Halonen

et al. 2024

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“…More recently, patients have been successfully transitioned to Teysuno, a similar fluoropyrimidine analog, with notably reduced rates of vasospasm. This has resulted in the European Society of Medical Oncology recommending that patients who experience cardiovascular toxicity during therapy with capecitabine or 5-FU be switched to Teysuno without any attempt to rechallenge patients with capecitabine or 5-FU [ 15 ]. However, this medication has not yet been approved in the United States for treatment of pancreatic neuroendocrine tumors as seen with our patient [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm

Thomesen,

Kisling,

Conte

et al. 2023

Am J Case Rep

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Patient: Male, 45-year-old Final Diagnosis: Vasospastic angina Symptoms: Chest pain • dyspnea • stable angina Clinical Procedure: Coronary angiography • graded exercise test Specialty: Cardiology • General and Internal Medicine Objective: Unusual or unexpected effect of treatment Background: Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. Case Report: We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but suspicion for coronary vasospasm persisted due to the temporal relationship with drug initiation and symptom characteristics. A graded exercise test reproduced his symptoms, accompanied by hyperacute peaked T waves and subsequent ST segment elevations in the inferior leads. Coronary angiography revealed patent coronary arteries, rendering provocative testing unnecessary due to a high clinical suspicion of capecitabine-induced vasospasm. Discontinuing the patient’s medication was a more efficient approach than continuing additional cardiac workup while the drug was still administered. After multidisciplinary discussion, capecitabine was discontinued, leading to symptom resolution and a negative repeat graded exercise test. Conclusions: This case underscores the potential for capecitabine to induce coronary artery vasospasm, emphasizing the importance of prompt medication cessation. Patients receiving capecitabine therapy and experiencing chest pain should undergo an evaluation with consideration of capecitabine-induced vasospasm in the differential diagnosis. Prompt recognition and medication cessation are critical to prevent serious cardiovascular complications including death. In our patient, discontinuing capecitabine resolved his symptoms, emphasizing the significance of discontinuing the causative drug and seeking alternative chemotherapy regimens.

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“…More recently, following trial evidence of efficacy and safety of the oral fluoropyrimidine S-1 in Western patients [ 49 – 51 ], additional descriptive RWE on long-term safety and cardiotoxicity recurrence supported EMA approval [ 52 – 54 ]. The ESMO guideline now recommends switching to S-1 in patients with mCRC who experience hand-foot syndrome or cardiovascular toxicity while being treated with capecitabine or 5-FU [ 39 , 55 ].…”

Section: Using Rwd For Treatment Effect Evaluationmentioning

confidence: 99%

Harnessing the Potential of Real-World Evidence in the Treatment of Colorectal Cancer: Where Do We Stand?

van Nassau,

Bol,

van der Baan

et al. 2024

Curr. Treat. Options in Oncol.

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Opinion statementTreatment guidelines for colorectal cancer (CRC) are primarily based on the results of randomized clinical trials (RCTs), the gold standard methodology to evaluate safety and efficacy of oncological treatments. However, generalizability of trial results is often limited due to stringent eligibility criteria, underrepresentation of specific populations, and more heterogeneity in clinical practice. This may result in an efficacy-effectiveness gap and uncertainty regarding meaningful benefit versus treatment harm. Meanwhile, conduct of traditional RCTs has become increasingly challenging due to identification of a growing number of (small) molecular subtypes. These challenges—combined with the digitalization of health records—have led to growing interest in use of real-world data (RWD) to complement evidence from RCTs. RWD is used to evaluate epidemiological trends, quality of care, treatment effectiveness, long-term (rare) safety, and quality of life (QoL) measures. In addition, RWD is increasingly considered in decision-making by clinicians, regulators, and payers. In this narrative review, we elaborate on these applications in CRC, and provide illustrative examples. As long as the quality of RWD is safeguarded, ongoing developments, such as common data models, federated learning, and predictive modelling, will further unfold its potential. First, whenever possible, we recommend conducting pragmatic trials, such as registry-based RCTs, to optimize generalizability and answer clinical questions that are not addressed in registrational trials. Second, we argue that marketing approval should be conditional for patients who would have been ineligible for the registrational trial, awaiting planned (non) randomized evaluation of outcomes in the real world. Third, high-quality effectiveness results should be incorporated in treatment guidelines to aid in patient counseling. We believe that a coordinated effort from all stakeholders is essential to improve the quality of RWD, create a learning healthcare system with optimal use of trials and real-world evidence (RWE), and ultimately ensure personalized care for every CRC patient.

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Fluoropyrimidine-induced hand-foot syndrome and cardiotoxicity: recommendations for the use of the oral fluoropyrimidine S-1 in metastatic colorectal cancer

Cited by 4 publications

References 49 publications

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm

Harnessing the Potential of Real-World Evidence in the Treatment of Colorectal Cancer: Where Do We Stand?

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