KRAS突变对晚期结直肠癌C225联合化疗疗效的影响

目的探讨KRAS基因状态与含西妥昔单抗（C225）的化疗方案治疗晚期结直肠癌患者的疗效相关性及药物安全性。方法总结2006年5月至2009年3月期间采用含C225化疗方案治疗81例晚期转移性结直肠癌患者的疗效，分析其KRAS基因突变情况、KRAS与治疗有效率（RR）、无疾病进展生存（PFS）和总生存时间（OS）的相关性及药物不良反应。结果81例患者总RR为33．3％，一、二、三线以上使用C225的RR分别为57．1％、38．5％和22．0％。可行KRAS检测44例，KRAS突变20例（45％）。44例患者中有43例可评价疗效．其中KRAS突变型和野生型患者的RR分别为5．0％和43．5％（P=0．002）。突变型和野生型KRAS患者中位PFS分别为7．0周和18．6周（P=0．003），中位OS分别为15.2个月和17．3个月．差异无统计学意义（P=0．463）。治疗总体耐受性好，不良反应主要有白细胞减少、恶心呕吐和皮疹．KRAS突变型和野生型患者皮疹的发生率为40％和42％．差异无统计学意义（P=0．91）。结论含C225的化疗方案治疗晚期转移性结直肠癌患者耐受性好．KRAS野生型患者疗效肯定．PFS较KRAS突变型患者明显延长。

Effect of KRAS mutation on efficacy of Cetuximab combined with chemotherapy in advanced colorectal cancer patients

Objective To explore the relationship between KRAS gene status and efficacy of Cetuximab(C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225. Methods From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival(OS) and adverse reaction of C225 were analyzed retrospectively. Results All the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases(45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respoctively(P=0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P=0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance(P=0.463). The common adverse reactions were leucoponia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P=0.91). Conclusion C225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.