西妥昔单抗联合伊立替康为主方案治疗转移性结直肠癌

Cetuximab plus Irinotecan in Treatment of Metastatic Colorectal Cancer

目的观察西妥昔单抗联合伊立替康治疗晚期结直肠癌的疗效、安全性及KRAS基因突变与疗效的相关性。方法对经西妥昔单抗联合伊立替康为主方案治疗且可评价疗效的15例晚期结直肠癌患者进行疗效分析,并对其中12例患者进行KRAS基因测定,分析KRAS基因突变与疗效的相关性。结果 (1)疗效分析:15例患者治疗后取得部分缓解4例,病情稳定7例,疾病进展4例,客观有效率26.7%,疾病控制率73.3%,中位疾病进展时间16周。主要的不良反应是痤疮样皮疹、腹泻和骨髓抑制。痤疮样皮疹发生率为80%(12/15),腹泻发生率为46.7%(7/15),骨髓抑制发生率为60%(9/15)。在出现痤疮样皮疹的12例患者中,客观有效率为33.3%,疾病控制率为83.3%。(2)KRAS基因突变与疗效的相关性:12例患者进行KRAS基因检测中,KRAS基因野生型的患者7例,客观有效率为28.6%,疾病控制率为85.7%,中位疾病进展时间18周;KRAS基因突变的患者5例,疗效为部分缓解1例,客观有效率为20%,疾病控制率为60%,中位疾病进展时间为12周。因纳入病例数较少,两者比较差异无统计学意义。结论西妥昔单抗联合CPT-11为主方案对晚期结直肠癌患者有效。除痤疮样皮疹外,不良反应无明显增加。对于出现痤疮样皮疹患者提示获益可能。对于KRAS基因野生型的患者,预示西妥昔单抗联合CPT-11能获得良好的疗效,对于KRAS基因突变型的患者,预示西妥昔单抗联合CPT-11未能增加疗效。

Objective To evaluate the clinical efficacy and safety of cetuximab plus irinotecan in the treatment of metastatic colorectal cancer,and to investigate the correlation of KRAS mutation and clinical efficacy.Methods Analyzed the 15 patients of metastatic colorectal cancer with histologically confirmed diagnosis treated with cetuximab in combination with irinotecan or FOLFIRI regimen.KRAS mutation was detected in 12 tumor tissues and investigated the correlation of KRAS mutation and clinical efficacy.Results（1）Efficacy analysis：The objective response rate was 26.7%,4 patients with PR（partial response）,7 patients with SD（stable disease）and 4 patients with PD（progression disease）.The disease control rate was 73.3% and the median time of tumor progression was 16 weeks.The major toxicities were acneform eruptions,diarrhea and bone marrow depression,their incidence rate was 80%（12/15）.46.7%（7/15）and 60%（9/15）respectively.In 12 acneform eruptions patients,the objective response rate was 33.3% and the disease control rate was 83.3%.（2）Correlation of KRAS mutation and efficacy：KRAS gene was detected in 12 patients.7 patients of KRAS were wild type,and the objective response rate was 28.6%,the disease control rate was 85.7% and the median time of tumor progression was 18 weeks.5 patients of KRAS were mutation type,and the objective response rate was 20%,the disease control rate was 60% and the median time of tumor progression was 12 weeks.Because of less cases,the difference had no statistical significance.Conclusion Cetuximab in combination with irinotecan has clinically significant activity in patients with refractory metastatic colorectal cancer.The toxicity,except rash,is not more frequent among the patients receiving cetuximab in comb ination with irionotecan than irionotecan alone.Acneform eruptions maybe prognosticate clinical benefit.Therapeutic effect of the patients with wild type KRAS may superior to those patients with mutant type KRAS when receiving cetuximab therapy.