西妥昔单抗联合化疗治疗晚期结直肠癌的生存分析及KRAS对疗效的影响

 【目的】 探讨影响西妥昔单抗联合化疗治疗晚期结直肠患者的生存因素及KRAS基因状态对疗效的影响。【方法】收集2005年3月至2008年12月中山大学肿瘤防治中心接受西妥昔单抗联合化疗的晚期结直肠癌患者102例的临床资料,对可能影响预后的临床病理因素进行单因素及多因素生存分析;检测45例石蜡标本KRAS基因,比较不同KRAS状态有效率(ORR)、疾病控制率(DCR)、无进展生存(PFS)、总生存时间(OS)的差异。 【结果】 初诊时有肿瘤相关症状者较无症状者OS短(34.0个月vs 43.5个月,P = 0.03);初诊时临床分期高者OS短(Ⅱ、Ⅲ、Ⅳ的OS分别为88.5个月、51.0个月、22.5个月,P < 0.01);西妥昔单抗联合化疗达到疾病控制者较疾病进展者OS长(43.5个月vs 28.0个月,P < 0.01)。39例可检测标本的KRAS突变率为28.2%(11/39),野生型者的ORR、DCR均高于突变型者(ORR 42.9% vs 9.1%, P = 0.049; DCR 71.4% vs 36.4%, P = 0.046)。野生型的PFS较突变型长(5.0个月vs 2.5个月,P = 0.02),但OS差异无统计学意义(42.5个月vs 33.0个月,P = 0.80),KRAS状态不是独立的预后因素(P = 0.42)。【结论】 西妥昔单抗联合化疗治疗ACRC,疾病得到控制者预后好,KRAS野生型者ORR、DCR及PFS均优于突变型者,但两者的OS可能无显著差异,KRAS状态不是独立的预后因素。

Survival Analysis of Cetuximab Combined with Chemotherapy for Advanced Colorectal Cancer and Effect of KRAS on Treatment

【Objective】 To study the prognostic factors of advanced colorectal cancer (ACRC) accepting cetuximab combined with chemotherapy and effect of KRAS on efficacy of that regimen. 【Methods】 Clinical data of 102 ACRC patients, treated by cetuximab plus chemotherapy in Sun Yat-sen University Cancer Center from March 2005 to December 2008, were collected. The prognostic value of clinical factors was evaluated by univariate and multivariate analysis. The KRAS status of 45 paraffin-embedded specimens were tested and the difference in objective response rate (ORR), disease control rate (DCR), progress free survival (PFS) and overall survival (OS) between patients with wild type and mutant type of KRAS were compared. 【Results】 The OS of patients with cancer-associated symptom was shorter than those without (34.0 months vs 43.5 months,P = 0.03). The patients with advanced primary clinical stage had short OS (88.5 months, 51.0 months and 22.5 months for clinical stageⅡ, Ⅲ, and Ⅳ,P < 0.01). The OS of patients with DCR by cetuximab combined with chemotherapy was longer than that with PD (43.5 months vs 28.0 months,P < 0.01). The KRAS status of 39 cases were tested successfully and mutant rate was 28.2% (11/39). The ORR, DCR, and PFS of wild type KRAS were all better than those of mutant type KRAS (ORR 42.9% vs 9.1%,P = 0.049;DCR 71.4% vs 36.4%,P = 0.046; PFS, 5.0 months vs 2.5 months,P = 0.02). However, the difference of OS between wild and mutant type KRAS was not statistically significant (42.5 months vs 33.0 months,P = 0.80) and the status of KRAS was not an independently prognostic factor(P = 0.42). 【Conclusions】 ACRC patients with DCR by cetuximab combined with chemotherapy had good prognosis. The ORR, DCR and PFS of wild type KRAS were all better than those of mutant type KRAS, but the difference of OS was not significant and the status of KRAS was not an independently prognostic factor.