BACKGROUND:Brain metastases commonly occur in non-small cell lung cancer (NSCLC), and patient prognosis is poor. Erlotinib, a specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, has shown antitumor activity in advanced NSCLC. This study evaluates erlotinib in the treatment for brain metastases from NSCLC. PATIENTS AND METHODS:We retrospectively reviewed 40 NSCLC patients with brain metastases. All were treated with oral erlotinib and followed until disease progression, death, or intolerable side effects. EGFR mutations within surgical specimens were retrospectively examined in 9 patients. RESULTS:For intracranial diseases, partial response (PR) was observed in 4 patients (10%), stable disease (SD) in 21 (52.5%), and progressive disease in 15 (37.5%), with an objective response rate of 10% and a disease control rate (DCR) of 62.5%. For extracranial diseases, DCR was observed in 17 patients (42.5%) (3 PRs+14 SDs) and progressive disease in 23 patients (57.5%). DCR within brain lesions in patients with activating EGFR mutations was 80% (1 PR+3 SDs), compared with 25% (1 SD) in patients with negative EGFR mutation. The median progression-free survival and median survival were 3.0 months and 9.2 months, respectively. There were no clinical factors associated with the response to erlotinib and survival as well (all P>0.05), whereas only the DCR in the brain was related to survival in multivariate analysis (P=0.000). CONCLUSIONS:Erlotinib is modestly active and well-tolerated by NSCLC patients with brain metastases. Erlotinib seems to be more effective in patients with activating EGFR mutations. Erlotinib may be an alternative to traditional treatments in this patient population.

译文

背景:脑转移通常发生在非小细胞肺癌(NSCLC)中,患者预后较差。厄洛替尼是一种与表皮生长因子受体相关的酪氨酸激酶的特异性抑制剂,已在晚期NSCLC中显示出抗肿瘤活性。这项研究评估了厄洛替尼在治疗非小细胞肺癌脑转移中的作用。
方法回顾性分析40例NSCLC脑转移患者。所有患者均接受口服厄洛替尼治疗,直至疾病进展,死亡或无法忍受的副作用为止。回顾性分析了9例患者的手术标本中的EGFR突变。
结果:对于颅内疾病,4例患者(10%)观察到部分反应(PR),21例(52.5%)观察到稳定疾病(SD),15例(37.5%)观察到进展性疾病,客观缓解率为10 ,疾病控制率(DCR)为62.5%。对于颅外疾病,在17例患者(42.5%)(3 PRs 14 SDs)中观察到DCR,在23例患者中(57.5%)观察到进行性疾病。 EGFR活化突变患者脑部病变的DCR为80%(1 PR 3 SDs),而EGFR突变阴性患者脑部DCR为25%(1 SD)。中位无进展生存期和中位生存期分别为3.0个月和9.2个月。在多变量分析中,也没有与厄洛替尼反应和生存相关的临床因素(所有P> 0.05),而只有脑中的DCR与生存有关(P = 0.000)。
结论:厄洛替尼在患有脑转移的非小细胞肺癌患者中适度活跃,且耐受性良好。厄洛替尼似乎在激活EGFR突变的患者中更有效。在该患者人群中,厄洛替尼可能是传统治疗的替代方法。

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