Clinical trial NCT04260269: Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study
Official title: Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity in Patients with Solid Tumors: a Retrospective, International and Non-interventional Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Solid Tumor
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Tampere University Hospital
First posted: 2020-02-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients who fulfil the following inclusion criteria will be included in the database until the target number of patients has been included:

* Solid tumor
* Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment
* Re-challenge with a different fluoropyrimidine-based treatment. Primary endpoint is switch to S-1 and secondary any fluoropyrimidine population.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

• Participation in a trial with experimental drugs

Primary outcomes:
measure: Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment
timeFrame: After switch to and during one line of S-1 based chemotherapy (average 6 months)
Secondary outcomes:
measure: Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine
timeFrame: After switch to and during one line of another fluoropyrimidine regimen (average 6 months)
measure: Cardiac symptoms during fluoropyrimidine chemotherapy
timeFrame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
measure: Diagnostic work-up
timeFrame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
measure: Time-lines for cardiotoxicity
timeFrame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
measure: Dose-intensity
timeFrame: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity
measure: Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity
timeFrame: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tampere
country: Finland
facility: Department of Oncology
state: Pirkanmaa
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
state: Uusimaa
city: Oulu
country: Finland
facility: Oulu university hospital
city: Turku
country: Finland
facility: Turku university hospital
city: Reykjavík
country: Iceland
facility: Landspitali
city: Dublin
country: Ireland
facility: St. Vincents University Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Lund
country: Sweden
facility: Skone university hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall hospital
city: Uppsala
country: Sweden
facility: Uppsala academic hospital
Study officials:
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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 therapy in patients with solid tumours: a multicentre retrospective observational cohort study. ESMO Open. 2022 Jun;7(3):100427. doi: 10.1016/j.esmoop.2022.100427. Epub 2022 Mar 30.