Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

Официальное название

Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity in Patients with Solid Tumors: a Retrospective, International and Non-interventional Study

Обзор

The purpose of the present study is to evaluate cardiotoxicity during re-challenge of a different modality of fluoropyrimidine (primary end-point S-1 and secondary any other fluoropyrimidine) after having perceived cardiotoxicity with a fluoropyrimidine based regimen previously. The patient population is being treated for solid tumors.

Подробное описание

Fluoropyrimidine chemotherapy agents, such as 5-fluorouracil and capecitabine, are occasionally associated with cardiotoxicity that may manifest as chest pain, ECG alterations, cardiac arrhythmia, and rarely myocardial infarction and sudden death. Clinical fluoropyrimidine cardiotoxicity is infrequent (1-8% of patients), but subclinical toxicity may be much more common (up to one third of patients). The underlying mechanisms are not well understood, but they may include abnormal coronary artery contractility or spasm, and myocardial toxicity. Cardiotoxicity may be less frequent with S-1 (a combination of tegafur, gimeracil and oteracil at a molar ratio of 1:0.4:1) as compared with 5-fluorouracil and capecitabine, but head-to-head comparisons are lacking.

Anecdotal evidence suggests that patients who have cardiotoxicity on other fluoropyrimidines may be successfully treated with S-1. The purpose of this retrospective study is to compare different 5-fluorouracil-based dosing modalities and S-1, and compare cardiotoxicity during these treatments.

The patient population was treated for solid tumors with a 5-fluorouracil based regimen and had a cardiac event grade 1-4. All patients were re-challenged with a different fluoropyrimidine or S-1 and assessed for cardiotoxicity during re-challenge.

Вмешательства

• Препарат Fluoropyrimidine
  This is the assessment of a specific evaluation of cardiac safety for patients with solid tumors who have experienced cardiotoxicity grade 1-4 during treatment with a fluoropyrimidine based treatment and are re-challenged with a different fluoropyrimidine. This multicentre, retrospective database is built to assess the impact on the cardiac and global safety of two different fluoropyrimidine based treatment regimens, of which the first has caused cardiotoxicity grade 1-4. Cardiac data will be

Первичные конечные точки

• Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment [Срок оценки: After switch to and during one line of S-1 based chemotherapy (average 6 months)]

Вторичные конечные точки (6)

• Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine [Срок оценки: After switch to and during one line of another fluoropyrimidine regimen (average 6 months)]
• Cardiac symptoms during fluoropyrimidine chemotherapy [Срок оценки: During one line of fluoropyrimidine based chemotherapy (average 6 months)]
• Diagnostic work-up [Срок оценки: During one line of fluoropyrimidine based chemotherapy (average 6 months)]
• Time-lines for cardiotoxicity [Срок оценки: During one line of fluoropyrimidine based chemotherapy (average 6 months)]
• Dose-intensity [Срок оценки: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity]
• Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity [Срок оценки: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity]

Критерии участия

Критерии включения

• Solid tumor
• Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment
• Re-challenge with a different fluoropyrimidine-based therapy

Критерии исключения

• Participation in a trial with experimental drugs

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Финляндия · 4 центра

• Department of Oncology — Tampere
• Helsinki University Central Hospital — Helsinki
• Oulu university hospital — Oulu
• Turku university hospital — Turku

Швеция · 4 центра

• Skone university hospital — Lund
• Karolinska University Hospital — Stockholm
• Sundsvall hospital — Sundsvall
• Uppsala academic hospital — Uppsala

Дания · 1 центр

• Odense University Hospital — Odense

Iceland · 1 центр

• Landspitali — Reykjavik

Ирландия · 1 центр

• St. Vincents University Hospital — Dublin

Нидерланды · 1 центр

• Academic Medical Center — Amsterdam

Норвегия · 1 центр

• Haukeland University Hospital — Bergen

Публикации

• Kwakman JJM, Baars A, van Zweeden AA, de Mol P, Koopman M, Kok WEM, Punt CJA. Case series of patients treated with the oral fluoropyrimidine S-1 after capecitabine-induced coronary artery vasospasm. Eur J Cancer. 2017 Aug;81:130-134. doi: 10.1016/j.ejca.2017.05.022. Epub 2017 Jun 15. No abstract available. PMID 28623776
• Kwakman JJ, Simkens LH, Mol L, Kok WE, Koopman M, Punt CJ. Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group. Eur J Cancer. 2017 May;76:93-99. doi: 10.1016/j.ejca.2017.02.009. Epub 2017 Mar 10. PMID 28286287
• Winther SB, Zubcevic K, Qvortrup C, Vestermark LW, Jensen HA, Krogh M, Sorbye H, Pfeiffer P; Academy of Geriatric Cancer Research (AgeCare). Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review. Acta Oncol. 2016 Jul;55(7):881-5. doi: 10.3109/0284186X.2016.1161825. Epub 2016 May 16. PMID 27181284
• Ye JX, Liu AQ, Ge LY, Zhou SZ, Liang ZG. Effectiveness and safety profile of S-1-based chemotherapy compared with capecitabine-based chemotherapy for advanced gastric and colorectal cancer: A meta-analysis. Exp Ther Med. 2014 May;7(5):1271-1278. doi: 10.3892/etm.2014.1576. Epub 2014 Feb 24. PMID 24940424
• Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009 Jun 16;53(24):2231-47. doi: 10.1016/j.jacc.2009.02.050. PMID 19520246
• Deboever G, Hiltrop N, Cool M, Lambrecht G. Alternative treatment options in colorectal cancer patients with 5-fluorouracil- or capecitabine-induced cardiotoxicity. Clin Colorectal Cancer. 2013 Mar;12(1):8-14. doi: 10.1016/j.clcc.2012.09.003. Epub 2012 Oct 26. PMID 23102544
• Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev. 2013 Dec;39(8):974-84. doi: 10.1016/j.ctrv.2013.03.005. Epub 2013 Apr 10. PMID 23582737
• Osterlund P, Kinos S, Pfeiffer P, Salminen T, Kwakman JJM, Frodin JE, Shah CH, Sorbye H, Ristamaki R, Halonen P, Soveri LM, Heerva E, Algars A, Barlund M, Hagman H, McDermott R, O'Reilly M, Rockert R, Liposits G, Kallio R, Flygare P, Teske AJ, van Werkhoven E, Punt CJA, Glimelius B. Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based th PMID 35798468

Идентификаторы

NCT: NCT04260269 · R18045

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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