[Fluoropyrimidines cardiac toxicity: 5-fluorouracil, capecitabine, compound S-1 and trifluridine/tipiracil]

Abstract

The incidence of cardiac toxicity of 5-flurorouracil (5-FU) IV and capecitabine varies from 1.2 to 18%. The physiopathology of this toxicity is still under study, various hypotheses are mentioned. In the absence of identified prophylactic treatment, reintroduction of this cytotoxic is at risk. A discussion between oncologists and cardiologists is essential to estimate the balance between benefit and risk and the careful reintroduction of treatment. An alternative compound might be raltitrexed which is currently the treatment recommended in case of intolerance to fluoropyrimidines. The compound S-1 does not have any cardiac toxicity. Of a total of 2910 patients in phase II or III studies, no grade III or IV cardiovascular events were reported. However, the treatment is not reimbursed in France and therefore not available. The trifluridine/tipiracil, for which approval from French authorities was obtained in November 2016 for patients with metastatic colorectal cancer in progress despite standard treatment lines, does not appear to have cardiac toxicity according to studies published to date. The pivotal phase III study (RECOURSE), that led to this marketing authorization, was performed in 800 patients with metastatic colorectal cancer refractory and only one patient (less than 1% of patients) treated with trifluridine/tipiracil presented an episode of cardiac ischemia. Thus, trifluridine/tipiracil, which is well tolerated, could be an alternative to raltitrexed for patients with cardiovascular history contraindicating or discouraging the use of fluoropyrimidines.

Keywords: Angina; Angor; Cardiotoxicity; Cardiotoxicité; Composé S-1; Fluoropyrimidine; S-1; Trifluridine/tipiracil.