氟尿嘧啶联合紫杉类或铂类药物治疗进展期胃癌的心脏毒性研究

Cardiotoxicity of fluorouracil combined with taxanes or platinum in treatment of advanced gastric cancer

目的分析接受氟尿嘧啶类药物为基础方案化疗的胃癌患者心脏毒性的发生情况,并探讨其可能的危险因素以及联合或者不联合紫杉类药物对其的影响。方法回顾2011年1月至2016年10月北京大学第一医院肿瘤化疗科连续收治的进展期胃癌患者中接受氟尿嘧啶类药物为基础方案化疗的患者,分析其心脏毒性发生情况以及联合或不联合紫杉类药物时心脏毒性事件发生率的差异。将出现严重心脏毒性的患者采用1:2的比例运用倾向性评分匹配(PSM)方法与无严重心脏毒性者进行匹配,匹配因素为年龄,采用Logistic后退法回归分析,探寻严重心脏事件的可能独立危险因素。结果研究共纳入128例患者,接受化疗1~18周期,中位接受化疗6周期。共38例(29.7%)患者发生心脏毒性事件,12例(9.4%)发生严重心脏事件,2例(1.6%)死于心脏毒性。氟尿嘧啶类药物联合紫杉类与联合铂类的两种方案间,各级别心脏毒性及严重心脏事件的发生率比较,差异均无统计学意义(P> 0.05)。经PSM法匹配年龄后进行多因素分析,结果显示严重心脏事件的独立危险因素为美国东部肿瘤协作组体力状态评分(ECOG PS)≥2分(OR=9.795,95%CI:1.283~74.772,P=0.028)和≥3度中性粒细胞减少(OR=8.374,95%CI:1.183~59.279,P=0.033)。结论 ECOG PS≥2分和≥3度中性粒细胞减少是进展期胃癌患者发生化疗相关严重心脏毒性的独立危险因素。本研究未发现紫杉类药物与铂类药物在心脏毒性发生率上的差异。

Objective To investigate the incidence rate of and risk factors for cardiotoxicity of fluorouracil-based chemotherapy in patients with locally advanced or metastatic gastric cancer, and the effects of combination with and without taxanes. Methods We retrospectively analyzed consecutive patients with locally advanced or metastatic gastric cancer treated with multiple cycles of fuorouracil-based chemotherapy at Peking University First Hospital from January 2011 to October 2016. The incidence rate of cardiotoxicity and the difference in cardiotoxicity events and severe cardiac events between the regimens in combination with or without taxanes were analyzed. Propensity score matching(PSM) was used to match patients with severe cardiac toxicity at a 1:2 ratio with patients without severe cardiac toxicity. The matching factor was age. Multivariate Logistic regression was used to identify independent risk factors for severe cardiac toxicity. Results A total of 128 patients were enrolled in this study. A median of six chemotherapy cycles were administered(range, 1–18 cycles). Cardiotoxicity was observed in 38(29.7%) of 128 patients. 12(9.4%) patients exhibited severe cardiac toxicity, and 2(1.6%) patients died of cardiac toxicity. There was no difference in the incidence rate of cardiac toxicity or severe cardiac toxicity between fluorouracil treatments combined with taxanes or with platinum(P > 0.05). The independent risk factors for severe cardiac toxicity identified by multivariable analysis were Eastern Cooperative Oncology Group performance status(ECOG PS) ≥ 2(OR=9.795, 95% CI: 1.283-74.772, P=0.028) and grade ≥ 3 neutropenia(OR=8.374, 95% CI: 1.183-59.279, P=0.033). Conclusion ECOG PS ≥ 2 and grade ≥ 3 neutropenia are independent risk factors for chemotherapy-related severe cardiotoxicity in patients with advanced gastric cancer. There is no significant difference in the incidence of cardiotoxicity between fuorouracil-based chemotherapy containing taxanes and that containing platinum.