2157P - A phase II randomised controlled trial comparing the cardiotoxicity of capecitabine and S-1

Background

Fluoropyrimidines are used widely to treat cancer but their cardiotoxicity, which remains incompletely understood, has serious consequences for some patients. The fluoropyrimidine S-1 (Teysuno®) has recently been approved for the management of colorectal cancer in patients who develop cardiovascular toxicity with other fluoropyrimidines.

Methods

This was a single-centre phase II prospective randomised open-label blinded endpoint trial that investigated the cardiotoxicity of capecitabine and S-1 in patients treated between May 2014 and March 2020. Patients were randomized 1:1 to receive oral capecitabine or S-1, alone or with oxaliplatin, for days 1-14 of a 21-day cycle. Baseline computed tomography coronary angiogram (CTCA) was performed. Myocardial ischaemia was quantified by ST-segment analysis of continuous 12-lead electrocardiography before and during days 3-5 of oral chemotherapy, by a blinded analyst. Alpha-fluoro-beta-alanine (FBAL) was measured using a validated liquid chromatography tandem mass spectrometry method.

Results

Fifty-nine patients (29 capecitabine; 30 S-1; mean age 64 years (range 40-83)) were enrolled, 56 started treatment and 72% (capecitabine) and 70% (S-1) received oxaliplatin. CTCA was performed in 53 patients, coronary artery disease (CAD) was seen in 30 (capecitabine, n=14/26; S-1, n=16/27). Duration of ST change was not significantly different between groups (p = 0.2198) but change in mean daily ischaemic burden (p=0.0442) was significantly higher for capecitabine compared to S-1. Ischaemic burden was unrelated to the presence of underlying CAD. FBAL (precursor to cardiotoxic fluoroacetate) was significantly increased with capecitabine compared to S-1 during treatment (Table).

Table: 2157P

Mean FBAL (ng/mL) during fluoropyrimidine treatment

Conclusions

In this prospective randomised trial, capecitabine was associated with significantly higher ischaemic burden and higher levels of FBAL than S-1 and this was unrelated to presence of CAD.

Clinical trial identification

NCT01845337.

Editorial acknowledgement

Wilco Coers, Meducom.

Legal entity responsible for the study

ACCORD, NHS Lothian R+D and the University of Edinburgh.

Funding

Nordic Pharma.

Disclosure

S. Clive: Non-Financial Interests, Personal and Institutional, Research Funding: Nordic. All other authors have declared no conflicts of interest.