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

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。     

The epothilones: new therapeutic agents for castration-resistant prostate cancer

The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy and durability with currently available therapeutics. The epothilones represent a novel class of anticancer therapy that stabilizes microtubules, causing cell death and tumor regression in preclinical models. The structure of the tubulin-binding site for epothilones is distinct from that of the taxanes. Moreover, preclinical studies suggest nonoverlapping mechanisms of resistance between epothilones and taxanes. In early-phase studies in patients with CRPC, treatment with ixabepilone, a semisynthetic analog of epothilone B, induced objective responses and prostate-specific antigen declines in men previously progressing on docetaxel-based regimens. Clinical activity has been observed in nonrandomized trials for patients with CRPC using ixabepilone in the first- and second-line settings as a single agent and in combination with estramustine. Patupilone and sagopilone were also shown to have promising efficacy in phase II clinical trials of patients with CRPC. All three epothilones appear to be well tolerated, with modest rates of neutropenia and peripheral neuropathy. The lack of crossresistance between epothilones and taxanes may allow sequencing of these agents. Evaluating epothilones in phase III comparative trials would provide much-needed insight into their potential place in the management of patients with CRPC.