厄洛替尼加减脑部放疗治疗非小细胞肺癌脑转移临床观察

Clinical observation of erlotinib ± brain radiotherapy for non-small cell lung cancer patients with brain metastases

目的 回顾性分析厄洛替尼加减脑部放疗治疗非小细胞肺癌脑转移患者的疗效和不良反应.方法 56例经病理学证实的非小细胞肺癌伴脑转移患者采用厄洛替尼治疗,其中联合脑部放疗者42例.观察其客观缓解率和疾病控制率.Kaplan-Meier法计算无进展生存率和总生存率并Logrank检验,Cox回归模型进行多因素分析.结果 56例患者脑病灶局部总体客观缓解率（ORR）57.1％ （32/56）,疾病控制率（DCR）82.1％ （46/56）,中位无疾病进展时间12.3个月,中位生存时间8.0个月.1年、2年无进展生存率为51.0％、20.0％.1年、2年总生存率为36.0％、7.0％.单发脑转移者DCR高于多发脑转移者（P =0.044）,而男性DCR高于女性（P =0.009）.ORR和DCR在不吸烟者、卡氏评分≥70分者、递归分隔分析（RPA）分级好者均高于吸烟者、卡氏评分＜70分者、RPA分级差者（P=0.043、P=0.001、P＜0.001;P=0.009、P＜0.001、P＜0.001）.单因素分析卡氏评分≥70分患者的无进展生存率和总生存率均高于卡氏评分＜70分者（P＜0.001和P＜0.001）.RPA分级好者的无进展生存率和总生存率更高（P＜0.001和P＜0.001）.不吸烟、腺癌患者的总生存率高于吸烟、鳞癌患者（P =0.007,P=0.047）.多因素分析显示卡氏评分状况是无进展生存期、总生存期的独立影响因素（P＜0.001和P=0.005）.病理类型是无进展生存期的独立影响因素（P =0.001）.结论 厄洛替尼对非小细胞肺癌脑转移患者有较好的疗效和安全性,其中男性、单发脑转移者DCR更高,而不吸烟者、卡氏评分≥70分者、RPA分级好者ORR和DCR均较高.卡氏评分状况是总生存期和无进展生存期的独立影响因素.腺癌患者较鳞癌患者能够得到更长的无进展生存期.

Objective To retrospectively evaluate the efficacy in non-small cell lung cancer （NSCLC） patients with brain metastases treated with erlotinib ± whole brain radiotherapy,and observe the adverse events.Methods From March 2012 to January 2015,56 patients with NSCLC with brain metastases received oral erlotinib,at a dose of 150mg per day till disease progression or intolerable adverse events were developed,including 42 cases who had received brain radiotherapy.The objective response rate （ORR） and disease control rate （DCR） were observed between groups,the progression-free survival （PFS） and overall survival （OS） were calculated by Kaplan-Meier method with the use of log-rank method.Prognostic factors of the patients were analyzed with univariate and multivariate analysis in Cox regression model.Curative effect was evaluated with response evaluation criteria in solid tumors （RECIST） criteria,and adverse events with National Cancer Institute （NCI） criteria.Results ORR and DCR were 57.1% （32/56）,and 82.1% （46/56）,respectively.The median PFS was 12.3 months,and the OS was 8.0 months.The 1-,and 2-year PFS rates were 51.0%,and 20.0%,respectively.The 1-,and 2-year year OS rates were 36.0%,and 7.0%,respectively.Men had a higher DRR rate than women （P =0.009）.Single brain metastasis patients had higher DCR rate than in multiple brain metastases patients （P =0.044）.The non-smokers,less than Karnofsky （KPS） score of 70 and high recursive partitioning analysis （RPA） score groups had higher ORR （P =0.043,P 〈0.001,P 〈0.001） and DCR （P =0.009,P 〈0.001,P 〈0.001） rates than those of groups with smokers,less than KPS score of 70 and low RPA score,respectively.The other factors of ORR and DCR showed no significant statistical difference （P 〉 0.05）.Univariate analysis showed that there were higher PFS rate and OS rate in high RPA score group than in low RPA score group （P 〈 0.001,P 〈0.001）,and in KPS score of 70 and more group than in less than score of 70 group （P 〈 0.001,P 〈0.001）,respectively.The non-smokers and patients with adenocarcinoma group had longer OS times.Multivariate analysis showed that KPS score was the independent prognostic factor of PFS and OS （P 〈 0.001,P =0.005）,pathological type was the independent prognostic factor of PFS （P =0.001）.Conclusions Erlotinib is effective and safe for NSCLC patients with brain metastases.Men and the single brain metastasis patients,non-smokers,high KPS and RPA score groups had higher DCR rates.KPS score is the most important influencing factors for patients PFS and OS time.Women and the patients with adenocarcinoma have higher PFS rate than those of men and squamous cell carcinoma.