西妥昔单抗联合化疗治疗转移性结直肠癌疗效与K-ras状态的关系

背景与目的：随着西妥昔单抗联合化疗在转移性结直肠癌患者中的不断应用，预测其治疗疗效的研究也越来越深入。本文旨在探讨转移性结直肠癌患者肿瘤组织中K—ras基因表达状态（野生型或突变型）及其与西妥昔单抗联合化疗疗效之间的关系。方法：2006年3月02008年6月期间应用西妥昔单抗联合化疗治疗转移性结直肠癌27例。采用聚合酶链反应（PCR）技术和直接测序法检测肿瘤组织中K-ras基因表达状态。分析K—ras基因表达状态与西妥昔单抗联合化疗疗效之间的关系。结果：全组27例患者中，K-ras野生型15例（55．6％），K—FaS突变型12例（44．4％）。在K—FaS野生型中，西妥昔单抗联合化疗的总有效率（ORR）为66．7％，其中cR2例（13．3％），PR 8例（53．3％），中位无进展生存期（PFS）8个月。在K—ras突变型中，总有效率为25．0％，PR3例（25．0％），中位PFS4个月。在K—ras野生型转移性结直肠癌患者中应用西妥昔单抗联合化疗的疗效明显优于K—ras突变型患者。结论：K-ras野生型是西妥昔单抗联合化疗疗效良好的预测指标。在西妥昔单抗联合化疗前明确患者的K—ras基因状态有助于选择合适的患者，获得最佳疗效。

K-ras status and efficacy of cetuximab-containing regimen in the treatment of patients with metastatic colorectal cancer

Background and purpose: Cetuximab-containing regimen has been increasingly applied in the treatment of patients with metastatic colorectal cancer. Simultaneously, the predictive factors of outcome for cetuximab have been thoroughly researched. The aim of this study was to evaluate the relationship between K-ras status and efficacy of cetuximab containing regimen in the treatment of patients with metastatic eolorectal cancer. Methods: Between March 2006 and June 2008, twenty-seven patients with metastatic colorectal cancer were treated with cetuximab in combination with chemotherapy. The K-ras mutation status [wild-type (wt) or mutation (nat)] was examined by polymerase chain reaction (PCR) and direct sequencing. The influence of K-ras mutation status on efficacy of cetuximab-containing regimen was analyzed. Results: For 27 patiants in this cohort, K-ras wt was detected in 55.6% (15/27) cases and K-ras mt in 44.4% (12/27) cases. Statistically significant differences were found between the patients with K-ras wt and K-ras mt in terms of overall response rate (ORR) (66.7% vs 25.0%,P=0.035) and progression-free survival (PFS) (8 months vs 4 months, P=0.0028). However, there was no significant difference in overall survival (OS) (19 months vs 12 months, P>0.05). The most common treatment-related adverse effect was skin reaction, with incidence rate of 80.0% and 66.7% (P>0.05), respectively. No treatment related death was observed. Conclusion: K-ras mutation status is a predictive factor of good efficacy of cetuximab-containing regimen in the treatment of patients with metastatic colorectal cancer. Patients with K-ras wt could benefit from cetuximab in combination with chemotherapy.