Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, University of California San Diego Health, San Diego, California.
Ann Thorac Surg. 2018 Feb;105(2):418-424. doi: 10.1016/j.athoracsur.2017.08.052. Epub 2017 Dec 6.
Data from meta-analyses support the use of induction or adjuvant platinum-based chemotherapy for locally advanced non-small cell lung cancers (NSCLCs). This phase 2 study assessed the role of induction cisplatin and docetaxel followed by surgery in patients with resectable stage I to III NSCLCs, followed by 12 months of adjuvant erlotinib.
Patients with resectable stage I to III NSCLCs received cisplatin 80 mg/m, docetaxel 75 mg/m every 21 days for 3 cycles, followed by surgery, followed by adjuvant erlotinib for 12 months. The primary endpoint included safety. Long-term efficacy outcomes and exploratory analysis of intermediary endpoints are also reported (NCT00254384).
Forty-seven eligible patients received a median of 3 cycles of induction treatment, 37 underwent surgical resection, and only 21 received adjuvant erlotinib. Two patients died in the perioperative period (1 sepsis during chemotherapy, 1 acute respiratory distress syndrome postoperatively). Most common grade 3 to 5 toxicities during chemotherapy included hypokalemia (8%), infection (7%), and granulocytopenia (25%). During adjuvant erlotinib, 14% of patients experienced grade 2 rash. Median overall survival was 3.4 years. Major pathologic responses in the primary tumor were observed in 19% (7 of 37) of patients and correlated with improved long-term overall survival. Complete pathologic response in mediastinal/hilar nodes also correlated with superior survival.
Induction cisplatin and docetaxel was well tolerated. Adjuvant erlotinib did not improve outcomes compared with historical controls. Major pathologic response predicted for improved long-term survival and is a suitable intermediary endpoint for future phase 2 studies.
来自荟萃分析的数据支持对局部晚期非小细胞肺癌（NSCLC）使用诱导或辅助铂类化疗。这项 2 期研究评估了诱导顺铂和多西他赛后行手术治疗，随后接受 12 个月辅助厄洛替尼治疗可切除 I 期至 III 期 NSCLC 患者的作用。
可切除 I 期至 III 期 NSCLC 患者接受顺铂 80mg/m²，多西他赛 75mg/m²，每 21 天 1 次，共 3 个周期，然后进行手术，再接受 12 个月辅助厄洛替尼治疗。主要终点包括安全性。还报告了长期疗效结果和中间终点的探索性分析（NCT00254384）。
47 例符合条件的患者接受了中位数为 3 个周期的诱导治疗，37 例患者接受了手术切除，只有 21 例患者接受了辅助厄洛替尼治疗。2 例患者在围手术期死亡（1 例化疗期间发生败血症，1 例术后急性呼吸窘迫综合征）。化疗期间最常见的 3 级至 5 级毒性包括低钾血症（8%）、感染（7%）和粒细胞减少症（25%）。在接受辅助厄洛替尼治疗期间，14%的患者出现 2 级皮疹。中位总生存期为 3.4 年。37 例患者中有 19%（7 例）的原发肿瘤有主要病理反应，与长期总生存改善相关。纵隔/肺门淋巴结的完全病理反应也与生存获益相关。
诱导顺铂和多西他赛可耐受良好。与历史对照相比，辅助厄洛替尼并未改善结局。主要病理反应预测长期生存改善，是未来 2 期研究的合适中间终点。
