Gatzemeier Ulrich, Pluzanska Anna, Szczesna Aleksandra, Kaukel Eckhard, Roubec Jaromir, De Rosa Flavio, Milanowski Janusz, Karnicka-Mlodkowski Hanna, Pesek Milos, Serwatowski Piotr, Ramlau Rodryg, Janaskova Terezie, Vansteenkiste Johan, Strausz Janos, Manikhas Georgy Moiseevich, Von Pawel Joachim
Zentrum Fur Pneumologie Und Thoraxchirurgie, Krankenhaus D LVA, Germany.
J Clin Oncol. 2007 Apr 20;25(12):1545-52. doi: 10.1200/JCO.2005.05.1474.
Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non-small-cell lung cancer (NSCLC).
Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL).
A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild).
Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.
厄洛替尼是一种有效的表皮生长因子受体酪氨酸激酶抑制剂，具有单药抗肿瘤活性。临床前研究显示，厄洛替尼可增强化疗的细胞毒性。这项III期随机双盲安慰剂对照多中心试验评估了厄洛替尼联合顺铂和吉西他滨作为晚期非小细胞肺癌（NSCLC）一线治疗的疗效和安全性。
患者接受厄洛替尼（150mg/天）或安慰剂，联合最多六个21天周期的化疗（第1天和第8天给予吉西他滨1250mg/m²，第1天给予顺铂80mg/m²）。主要终点为总生存期（OS）。次要终点包括疾病进展时间（TTP）、缓解率（RR）、缓解持续时间和生活质量（QoL）。
共纳入1172例患者。基线人口统计学和疾病特征均衡良好。治疗组之间在OS（风险比，1.06；厄洛替尼组和安慰剂组的中位数分别为43周和44.1周）、TTP、RR或QoL方面无差异。在一小部分从不吸烟的患者中，厄洛替尼组的OS和无进展生存期有所延长；未发现其他更可能获益的亚组。厄洛替尼联合化疗总体耐受性良好；除厄洛替尼组皮疹和腹泻发生率增加（一般为轻度）外，各治疗组不良事件发生率相似。
对于未经化疗的晚期NSCLC患者，与单纯化疗相比，厄洛替尼联合顺铂和吉西他滨未显示出生存获益。
