Shukuya Takehito, Ko Ryo, Mori Keita, Kato Motoyasu, Yagishita Shigehiro, Kanemaru Ryota, Honma Yuichiro, Shibayama Rina, Koyama Ryo, Shimada Naoko, Takahashi Kazuhisa
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 3-1-3, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.
Clinical Trial Coordination Office, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Suntou-gun, Shizuoka, 411-8777, Japan.
Cancer Chemother Pharmacol. 2015 Oct;76(4):771-6. doi: 10.1007/s00280-015-2843-3. Epub 2015 Aug 11.
Docetaxel or pemetrexed monotherapy is recommended either as a second-line treatment for non-small cell lung cancer (NSCLC) patients without EGFR mutation or ALK fusion genes or as a third-line treatment for patients with EGFR mutation or ALK fusion. However, efficacy and survival for these two settings have not been compared, leaving it unclear whether these two populations can be included in the same clinical trials. Moreover, prognostic factors for patients who are recommended to receive docetaxel/pemetrexed monotherapy are largely unknown.
Docetaxel or pemetrexed was administered to 67 EGFR wild-type patients as a second-line treatment following one platinum-based combination chemotherapy and to 17 EGFR mutant patients as a third-line treatment following EGFR tyrosine kinase inhibitors and one platinum-based combination chemotherapy. Docetaxel and pemetrexed were administered at 60 and 500 mg/m(2), respectively, every 3 weeks until disease progression, intolerable toxicity, or patient refusal. Overall survivals (OSs) between the two groups were compared using the log-rank test, and prognostic factors were evaluated via Cox's proportional hazards models.
The median OS was 345.5 days in the EGFR wild-type second-line group and 616 days in the EGFR mutant third-line group. Multivariate analyses revealed that the stage before first-line treatment, performance status, and EGFR status were significant prognostic factors.
When planning clinical studies of NSCLC patients recommended to receive docetaxel or pemetrexed as single-agent chemotherapy, the EGFR status and stage before first-line treatment should be considered as stratification factors of randomized clinical studies.
多西他赛或培美曲塞单药治疗推荐用于无表皮生长因子受体(EGFR)突变或间变性淋巴瘤激酶(ALK)融合基因的非小细胞肺癌(NSCLC)患者的二线治疗,或用于EGFR突变或ALK融合患者的三线治疗。然而,这两种治疗方案的疗效和生存期尚未进行比较,因此尚不清楚这两类患者是否可纳入同一临床试验。此外,推荐接受多西他赛/培美曲塞单药治疗患者的预后因素大多未知。
67例EGFR野生型患者在接受一次铂类联合化疗后接受多西他赛或培美曲塞二线治疗,17例EGFR突变患者在接受EGFR酪氨酸激酶抑制剂和一次铂类联合化疗后接受多西他赛或培美曲塞三线治疗。多西他赛和培美曲塞分别以60mg/m²和500mg/m²的剂量每3周给药一次,直至疾病进展、出现无法耐受的毒性或患者拒绝治疗。采用对数秩检验比较两组的总生存期(OS),并通过Cox比例风险模型评估预后因素。
EGFR野生型二线治疗组的中位OS为345.5天,EGFR突变三线治疗组为616天。多因素分析显示,一线治疗前的分期、体能状态和EGFR状态是显著的预后因素。
在规划推荐接受多西他赛或培美曲塞单药化疗的NSCLC患者的临床研究时,EGFR状态和一线治疗前的分期应作为随机临床研究的分层因素。