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

*Corresponding author for this work

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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
JournalESMO Open
Volume7
Issue number3
Number of pages10
ISSN2059-7029
DOIs
Publication statusPublished - Jun 2022

Keywords

  • S-1
  • cardiac toxicity
  • cardiotoxicity
  • colorectal cancer
  • fluoropyrimidines
  • gastrointestinal cancer
  • Capecitabine/adverse effects
  • Humans
  • Middle Aged
  • Neoplasms/drug therapy
  • Male
  • Young Adult
  • Cardiotoxicity/etiology
  • Fluorouracil/adverse effects
  • Aged, 80 and over
  • Adult
  • Female
  • Aged
  • Retrospective Studies

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