奥沙利铂或伊立替康联合卡培他滨治疗转移性结直肠癌的临床研究

Differences in efficacy and safety between irinotecan and oxaliplatin when combined with capecitabine for the treatment of metastatic colorectal cancer

目的探讨奥沙利铂联合卡培他滨方案（Capox）与伊立替康联合卡培他滨方案（CAPIRI）在转移性结直肠癌治疗中的临床疗效、毒性反应及生存状况的差异。方法91例不可切除的转移性结直肠癌患者随机分为两组，A组（n=46，Capox方案）：奥沙利铂＋卡培他滨组，给予奥沙利铂130mg／m2，持续静脉滴注90min，第1天；卡培他滨1000mg／m-2，第1～14天，2次／d，口服，每3周为一周期。B组（n=45，CAPIRI方案）：伊立替康＋卡培他滨组，给予伊立替康250mg／m2，持续静脉滴注90min，第1天；卡培他滨1000mg／m2，第1～14天，2次／d，口服，每3周为一周期。结果88例患者疗效可评价，3例患者在第1周期结束后因难以耐受毒副反应而退出研究（Capox，n=1；CAPIRI，n=2）。Capox方案与CAPIRI方案的客观缓解率分别为46．7％和41．9％，疾病控制率分别为82．2％和81．4%，无统计学差异。2组的中位无进展生存期（PFS）分别为9个月和8．6个月，中位生存时间（OS）分别为18．5个月和17．5个月，二者相比无统计学差异。Capox方案组Ⅲ～Ⅳ度感觉神经病变的发生率较高（P=0．003），而CAPIRI组则以Ⅲ～Ⅳ度白细胞减少为主要毒性反应（P=0．017）。结论奥沙利铂或伊立替康联合卡培他滨方案对不可切除的转移性结直肠癌均具有较好的疗效，可有效改善预后，安全性好，毒副反应可耐受，用药方便，均可作为晚期结直肠癌化疗的有效选择。

Objective This randomized phase II trial investigate the efficacy, the side effects and the survival of the combination of oxaliplatin and Capecitabine（Capox） versus kinotecan and Capecitabine（CAPIRI） in patients with unresectable metastatic colorectal cancer. Methods 91 patients with histologic or cytologic comfirmation of unresectable metastatic colorectal cancer were randomly assigned to receive CAPOX [oxaliplatin 130 mg/m2 intravenously （i.v.） days 1 and capecitabine 1000 mg/m2 orally b.i.d, days 1-14; q21d] or CAPIRI [irinotecan 250 mg/m2 i.v. days l and capecitabine 1000 mg/m2 orally b.i.d, days 1-14; q21d].Each patient was received at least six cycles. Results 88 of 91 patients were assessable for response, three（Capox, n=1; CAPIRI, n=2） interrupted therapy soon after cycle 1 because of side effects and no clinical benefit. 2 complete responses （CRs） and 19 partial responses （PRs） were reported with CAPOX （ORR 46.7%）, and 2 CRs and 16 PRs with CAPIRI （ORR 41.9%; P=0.65）. Median progression-free survival was 9 months for CAPOX and 8.6 months for CAPIRI （P=0.538）, with median survival times of 18.5 months and 17.5 months （P=0.593）, respectively. Grade 3/4 sensory neuropathy as predominant toxic effect occurred in 17.4% of patients with Capox while neutropenia as predominant toxic effect occurred in 11.1% of patients with CAPIRI. Conelusion It was demonstrated that Capox and CAPIRI had similar efficacy in patients with unresectable metastatic colorectal cancer.