Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study
- Conditions
- Solid Tumor
- Registration Number
- NCT04260269
- Lead Sponsor
- Helsinki University Central Hospital
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 200
- Solid tumor
- Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment
- Re-challenge with a different fluoropyrimidine-based therapy
• Participation in a trial with experimental drugs
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment After switch to and during one line of S-1 based chemotherapy (average 6 months) Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to S-1
- Secondary Outcome Measures
Name Time Method Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine After switch to and during one line of another fluoropyrimidine regimen (average 6 months) Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to another fluoropyrimidine chemotherapy
Cardiac symptoms during fluoropyrimidine chemotherapy During one line of fluoropyrimidine based chemotherapy (average 6 months) Frequency and severity according to NCI-CTCAE of cardiac symptoms during different fluoropyrimidines and the correlation with other added cytotoxics or biologics
Diagnostic work-up During one line of fluoropyrimidine based chemotherapy (average 6 months) Diagnostic work-up for cardiotoxicity in real world data
Time-lines for cardiotoxicity During one line of fluoropyrimidine based chemotherapy (average 6 months) Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy
Dose-intensity During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity Dose-intensity of the therapy at the cycle causing cardiotoxicity
Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity The alterations of (if evaluated), graded as normal, non-significant abnormalities or significant abnormalities.:
* ECG abnormalities
* Ejection fraction in %
* Coronary artery status on angiogram
* Cardiac arrhythmias in ECG, Holter or cardiac monitor registration
* Plasma troponin concentration and other cardiac enzymes and other laboratory tests as within reference range ro abnormal
* Serum alpha-fluoro-beta-alanine (FBAL) concentration
Trial Locations
- Locations (13)
Department of Oncology
🇫🇮Tampere, Pirkanmaa, Finland
Turku university hospital
🇫🇮Turku, Finland
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Landspitali
🇮🇸ReykjavÃk, Iceland
Sundsvall hospital
🇸🇪Sundsvall, Sweden
Odense University Hospital
🇩🇰Odense, Denmark
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Haukeland University Hospital
🇳🇴Bergen, Norway
Skone university hospital
🇸🇪Lund, Sweden
Helsinki University Central Hospital
🇫🇮Helsinki, Uusimaa, Finland
Oulu university hospital
🇫🇮Oulu, Finland
St. Vincents University Hospital
🇮🇪Dublin, Ireland
Uppsala academic hospital
🇸🇪Uppsala, Sweden