TY - JOUR
T1 - Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours
T2 - a multicentre retrospective observational cohort study
AU - Osterlund, P.
AU - Kinos, S.
AU - Pfeiffer, P.
AU - Salminen, T.
AU - Kwakman, J. J. M.
AU - Frödin, J. E.
AU - Shah, C. H.
AU - Sorbye, H.
AU - Ristamäki, R.
AU - Halonen, P.
AU - Soveri, L. M.
AU - Heervä, E.
AU - Ålgars, A.
AU - Bärlund, M.
AU - Hagman, H.
AU - McDermott, R.
AU - O'Reilly, M.
AU - Röckert, R.
AU - Liposits, G.
AU - Kallio, R.
AU - Flygare, P.
AU - Teske, A. J.
AU - van Werkhoven, E.
AU - Punt, C. J. A.
AU - Glimelius, B.
N1 - Funding Information: The authors acknowledge the medical writers at Meducom BV, The Netherlands, Wilko Coers, PhD and Sandy Field, PhD, who were compensated for their support by Nordic Drugs and Nordic Pharma. This work was supported by Finska Läkaresällskapet (2016, 2018-2022), the Finnish Cancer Foundation (2019-2023), the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Turku, and Helsinki University Hospitals (2016-2022), Tampere University Hospital Fund (Tukisäätiö 2019, 2020, and OOO-project 2020), Research Fund of Helsinki University Hospital (2019, 2021, 2022), Relander's Foundation (2020-2022), and the infrastructure for the database and study nurse was partly supported by Nordic Drugs. The funders had no role in the study design, analysis, interpretation of the data, decision to publish, or writing of this report. All authors had full access to the data and had final responsibility for the decision to submit it for publication. All authors report institutional research funding from Nordic drugs paid to Tampere University Hospital and support for database, during the conduct of the study. PO, SK, PP, TS, JJMK, JEF, CHS, HS, RR, PH, LMS, EH, AÅ, MB, HH, RMD, MOR, RR, GL, RK, PF, AJK, EvW, CJAP, and BG report grants, personal fees, or non-financial support from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Eisai, Erytech Pharma, Fresenius, Incyte, Janssen-Cilag, Merck, Merck Sharp & Dohme, Nordic Drugs, Nordic Pharma, Nordic Group, Nutricia, Pierre-Fabre, Roche, Sanofi, Servier, Sobi, or Varian. The data collected for this study can be made available to others in de-identified form after all primary and secondary endpoints have been published, in the presence of a data transfer agreement, and if the purpose of use complies with Finnish and European legislation. Requests for data sharing can be made to the corresponding author, including a proposal that must be approved by the steering committee. Funding Information: This work was supported by Finska Läkaresällskapet (2016, 2018-2022), the Finnish Cancer Foundation (2019-2023), the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Turku, and Helsinki University Hospitals (2016-2022), Tampere University Hospital Fund (Tukisäätiö 2019, 2020, and OOO-project 2020), Research Fund of Helsinki University Hospital (2019, 2021, 2022), Relander’s Foundation (2020-2022), and the infrastructure for the database and study nurse was partly supported by Nordic Drugs. The funders had no role in the study design, analysis, interpretation of the data, decision to publish, or writing of this report. All authors had full access to the data and had final responsibility for the decision to submit it for publication. All authors report institutional research funding from Nordic drugs paid to Tampere University Hospital and support for database, during the conduct of the study. Publisher Copyright: © 2022 The Author(s)
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - S-1
KW - cardiac toxicity
KW - cardiotoxicity
KW - colorectal cancer
KW - fluoropyrimidines
KW - gastrointestinal cancer
UR - http://www.scopus.com/inward/record.url?scp=85127304914&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.esmoop.2022.100427
DO - https://doi.org/10.1016/j.esmoop.2022.100427
M3 - Article
C2 - 35798468
SN - 2059-7029
VL - 7
JO - ESMO open
JF - ESMO open
IS - 3
M1 - 100427
ER -