Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1395-401. doi: 10.1016/j.ijrobp.2010.01.014. Epub 2010 Jun 3.
To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC).
Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy.
Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%.
Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.
评估培美曲塞/顺铂/胸部放疗联合培美曲塞/顺铂巩固治疗不可切除的 IIIA/B 期非小细胞肺癌（NSCLC）的可行性和安全性。
符合条件的患者体重减轻<5%，表现状态良好，接受两个周期的培美曲塞（剂量水平 1、2 和 3/4 分别为第 1 天和第 22 天 300、400 或 500mg/m2）和顺铂（剂量水平 1-3 为第 1-3 天 25mg/m2；剂量水平 4 为第 1-5 天 20mg/m2），同时进行胸部放疗（31-35 个分次 61-66Gy）。巩固治疗包括两个周期的培美曲塞/顺铂（500mg/m2，75mg/m2），在同步治疗后 21 天进行。
2006 年 1 月至 2007 年 10 月期间，16 例患者入组研究。中位随访时间为 17.2 个月。未观察到剂量限制毒性。中位放疗剂量为 64Gy（范围 45-66Gy）。严重的 3/4 级血液学毒性发生率分别为 38%和 7%。1 例患者发生 3 级急性食管炎，2 例患者发生晚期（3 级）食管狭窄，经扩张治疗成功。1 例患者发生 3 级肺炎。总缓解率为 88%。1 年总生存率为 81%。
在 IIIA/B 期 NSCLC 中，培美曲塞全剂量联合顺铂和胸部放疗似乎是安全的。培美曲塞是该治疗方案中首个可耐受全剂量的第三代细胞毒药物。一项评估剂量水平 4 的 II 期研究正在进行中。
