Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study

P. Osterlund, S. Kinos, P. Pfeiffer, T. Salminen, J. J.M. Kwakman, J. E. Frödin, C. H. Shah, H. Sorbye, R. Ristamäki, P. Halonen, L. M. Soveri, E. Heervä, A. Ålgars, M. Bärlund, H. Hagman, R. McDermott, M. O'Reilly, R. Röckert, G. Liposits, R. KallioP. Flygare, A. J. Teske, E. van Werkhoven, C. J.A. Punt, B. Glimelius

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.

Original languageEnglish
Article number100427
Number of pages10
JournalEsmo Open
Volume7
Issue number3
DOIs
Publication statusPublished - 2022
Publication typeA1 Journal article-refereed

Keywords

  • cardiac toxicity
  • cardiotoxicity
  • colorectal cancer
  • fluoropyrimidines
  • gastrointestinal cancer
  • S-1

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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