Vaflard Pauline, Ederhy Stéphane, Torregrosa Cécile, André Thierry, Cohen Romain, Lopez-Trabada Daniel
AP-HP, hôpital Saint-Antoine, département d'oncologie médicale, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.
AP-HP, hôpital Saint-Antoine, service de cardiologie, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France.
Bull Cancer. 2018 Jul-Aug;105(7-8):707-719. doi: 10.1016/j.bulcan.2018.05.005. Epub 2018 Jun 28.
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.
5-氟尿嘧啶（5-FU）静脉注射和卡培他滨的心脏毒性发生率在1.2%至18%之间。这种毒性的生理病理学仍在研究中，有多种假说被提及。在缺乏明确的预防性治疗的情况下，重新使用这种细胞毒性药物存在风险。肿瘤学家和心脏病学家之间的讨论对于评估获益与风险的平衡以及谨慎重新引入治疗至关重要。一种替代化合物可能是雷替曲塞，它是目前在对氟嘧啶不耐受的情况下推荐的治疗药物。化合物S-1没有任何心脏毒性。在II期或III期研究的总共2910名患者中，未报告III级或IV级心血管事件。然而，该治疗在法国未被报销，因此无法获得。曲氟尿苷/替匹嘧啶于2016年11月获得法国当局批准，用于尽管接受了标准治疗方案但仍进展的转移性结直肠癌患者，根据迄今发表的研究，它似乎没有心脏毒性。导致该药物上市许可的关键III期研究（RECOURSE）在800名难治性转移性结直肠癌患者中进行，只有一名接受曲氟尿苷/替匹嘧啶治疗的患者（不到患者总数的1%）出现了心脏缺血发作。因此，耐受性良好的曲氟尿苷/替匹嘧啶对于有心血管病史而禁忌或不适合使用氟嘧啶的患者可能是雷替曲塞的一种替代药物。
