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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291631/ https://www.ncbi.nlm.nih.gov/pubmed/35798468 http://dx.doi.org/10.1016/j.esmoop.2022.100427 |
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author | Osterlund, P. Kinos, S. Pfeiffer, P. Salminen, T. Kwakman, J.J.M. Frödin, J.-E. Shah, C.H. Sorbye, H. Ristamäki, R. Halonen, P. Soveri, L.M. Heervä, E. Ålgars, A. Bärlund, M. Hagman, H. McDermott, R. O’Reilly, M. Röckert, R. Liposits, G. Kallio, R. Flygare, P. Teske, A.J. van Werkhoven, E. Punt, C.J.A. Glimelius, B. |
author_facet | Osterlund, P. Kinos, S. Pfeiffer, P. Salminen, T. Kwakman, J.J.M. Frödin, J.-E. Shah, C.H. Sorbye, H. Ristamäki, R. Halonen, P. Soveri, L.M. Heervä, E. Ålgars, A. Bärlund, M. Hagman, H. McDermott, R. O’Reilly, M. Röckert, R. Liposits, G. Kallio, R. Flygare, P. Teske, A.J. van Werkhoven, E. Punt, C.J.A. Glimelius, B. |
author_sort | Osterlund, P. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9291631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92916312022-07-19 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 Osterlund, P. Kinos, S. Pfeiffer, P. Salminen, T. Kwakman, J.J.M. Frödin, J.-E. Shah, C.H. Sorbye, H. Ristamäki, R. Halonen, P. Soveri, L.M. Heervä, E. Ålgars, A. Bärlund, M. Hagman, H. McDermott, R. O’Reilly, M. Röckert, R. Liposits, G. Kallio, R. Flygare, P. Teske, A.J. van Werkhoven, E. Punt, C.J.A. Glimelius, B. ESMO Open Original Research 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. Elsevier 2022-03-30 /pmc/articles/PMC9291631/ /pubmed/35798468 http://dx.doi.org/10.1016/j.esmoop.2022.100427 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Osterlund, P. Kinos, S. Pfeiffer, P. Salminen, T. Kwakman, J.J.M. Frödin, J.-E. Shah, C.H. Sorbye, H. Ristamäki, R. Halonen, P. Soveri, L.M. Heervä, E. Ålgars, A. Bärlund, M. Hagman, H. McDermott, R. O’Reilly, M. Röckert, R. Liposits, G. Kallio, R. Flygare, P. Teske, A.J. van Werkhoven, E. Punt, C.J.A. Glimelius, B. 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291631/ https://www.ncbi.nlm.nih.gov/pubmed/35798468 http://dx.doi.org/10.1016/j.esmoop.2022.100427 |
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