吉非替尼治疗50例非小细胞肺癌脑转移的临床分析

Analysis of gefitinib on brain metastases in 50 patients with non-small cell lung cancer

背景与目的:非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移较常见,预后不佳。吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂,多应用于治疗晚期NSCLC。本研究拟探讨吉非替尼治疗NSCLC脑转移的疗效、预后及其相关因素。方法:回顾性分析50例NSCLC脑转移患者的临床资料,所有患者均口服吉非替尼250mg/d,直到疾病进展、死亡或发生不可耐受的不良反应。疗效分析采用χ2检验,生存分析采用Kaplan-Meier法并进行Log-rank时序检验,用Cox比例风险模型进行多因素分析。结果:吉非替尼对颅内病灶的疗效为部分缓解5例(10%),疾病稳定37例(74%),疾病进展8例(16%),客观有效率为10%,疾病控制率为84%。全身病变的总体疗效为部分缓解5例(10%),疾病稳定30例(60%),疾病进展15例(30%),客观有效率为10%,疾病控制率为70%。总体疾病控制率与患者的PS评分、脑转移数目具有相关性(P分别为0.004和0.022),但与年龄、性别、吸烟状况、病理类型、脑转移时间、化疗及放疗与否和不良反应等临床特点未见有相关性(P均>0.05)。中位疾病进展时间为7.0个月,与患者的PS评分及吸烟状况具有相关性(P分别为0.000和0.045)。中位生存期为10.8个月,1、2年生存率分别为44%和6%。单因素分析显示生存期与患者的PS评分、吸烟状况和脑转移数目具有相关性(P分别为0.011、0.028和0.044),多因素分析则显示生存期与患者的PS评分、吸烟状况具有相关性(P分别为0.005和0.006),与脑转移数目接近有统计学意义(P=0.075)。结论:吉非替尼对NSCLC脑转移具有一定的疗效,功能状态良好(PS0～1分)的非吸烟患者具有较好的生存获益,单发脑转移的生存时间有好于多发脑转移的趋势。吉非替尼可以作为NSCLC脑转移的一种治疗选择。

Background and purpose：Brain metastases are common occurrences in patients with nonsmall cell lung cancer （NSCLC）. Gefitinib is a specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has been commonly used in the treatment for advanced NSCLC. The aim of this study was to evaluate the antitumor efficacy of gefitinib in NSCLC patients with brain metastases. Methods：Fifty NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with gefitinib, given orally at a daily dose of 250 mg. These patients discontinued administration of gefitinib when disease progression, death or intolerable side effects appeared. χ2 test was applied in response analysis. Survival analysis was compared with Kaplan-Meier method and Log-rank test respectively. The multivariate analysis was performed with Cox＇s proportion risk model. Statistical significance was defined as P〈0.05. Results：In terms of intracranial lesions, partial response （PR） was observed in 5 patients （10%）, stable disease （SD） in 37 patients （74%） and progressive disease （PD） in 8 patients （16%）, objective response rate （ORR） and disease control rate （DCG） were 10% and 84%, respectively. As for systemic disease, PD was observed in 5 patients （10%）, SD in 30 patients （60%） and PD in 15 patients （30%）, overall ORR and DCR were 10% and 70%, respectively. Overall DCG was related to the patients＇ PS score and the number of brain metastases （P=0.004, P=0.022）, but there was no statistical difference in overall DCR among different subtypes of age, gender, smoking history, histology, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects （P〉0.05）. The median time to disease progression （MTTP） was 7.0 months, which was related to the patients＇ PS score and smoking history （P=0.000, P=0.045）. The median survival time （MST） was 10.8 months, and 1-and 2-year survival rates were 44% and 6% respectively. The univariate analysis showed that the survival time was related to the patients＇ PS score, smoking history and the number of brain metastases （P=0.011, P=0.028, P=0.044）. The multivariate analysis indicated that both the patients＇ PS score and smoking history were two independent prognostic factors （P=0.005, P=0.006） and the relationship of the survival time and the number of brain metastases was near to statistical significance （P=0.075）. Conclusion：The patients with non-smoking history and favorable performance status（PS 0-1） may have better survival benefit and those with single brain metastasis have a trend to survive longer. Gefitinib may be effective on brain metastases in NSCLC patients and appears to be a possible new treatment option.