Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

Study Overview
=================
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.

Official Title
-----------------
Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity in Patients With Solid Tumors: A Retrospective, International and Non-interventional Study

Conditions
-----------------
Solid Tumor

Intervention / Treatment
-----------------
* Drug: Fluoropyrimidine


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 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 collected by medical record review from initiation of first fluoropyrimidine-based treatment and switch to second fluoropyrimidine-based treatment until death or last follow-up. Basic demographics, cancer and treatment information from the whole course of cancer until death or last follow-up.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment | Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to S-1 | After switch to and during one line of S-1 based chemotherapy (average 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine | Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to another fluoropyrimidine chemotherapy | After switch to and during one line of another fluoropyrimidine regimen (average 6 months) | 
| Cardiac symptoms during fluoropyrimidine chemotherapy | Frequency and severity according to NCI-CTCAE of cardiac symptoms during different fluoropyrimidines and the correlation with other added cytotoxics or biologics | During one line of fluoropyrimidine based chemotherapy (average 6 months) | 
| Diagnostic work-up | Diagnostic work-up for cardiotoxicity in real world data | During one line of fluoropyrimidine based chemotherapy (average 6 months) | 
| Time-lines for cardiotoxicity | Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy | During one line of fluoropyrimidine based chemotherapy (average 6 months) | 
| Dose-intensity | Dose-intensity of the therapy at the cycle causing cardiotoxicity | During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity | 
| Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity | 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 | During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity |