Instituto do Cancer Arnaldo Vieira de Carvalho, Sao Paolo, Brazil.
J Thorac Oncol. 2011 Nov;6(11):1907-14. doi: 10.1097/JTO.0b013e318226b5fa.
This study compared survival without toxicity in patients with advanced, nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin.
This multicenter, open-label, parallel-group, phase 3 trial comprised patients randomized (1:1) to pemetrexed/carboplatin (n = 128) or docetaxel/carboplatin (n = 132). Patients received treatment on day 1 of each 21-day cycle (maximum of six cycles). Treatment included carboplatin (area under the curve = 5 mg/ml × min) and pemetrexed (500 mg/m(2)) or docetaxel (75 mg/m(2)). The primary outcome measure, survival without treatment-emergent grade 3/4 toxicity, was defined as the time from randomization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test. The analysis population included 106 patients in the pemetrexed/carboplatin (Pem/Carb) group and 105 patients in the docetaxel/carboplatin (Doc/Carb) group.
Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group (log-rank p < 0.001; median survival without treatment-emergent grade 3/4 toxicity: 3.2 versus 0.7 months; adjusted hazard ratio = 0.45 [95% confidence interval: 0.34-0.61]). Overall survival was similar in the Pem/Carb versus the Doc/Carb group (log-rank p = 0.934; median survival: 14.9 versus 14.7 months; adjusted hazard ratio = 0.93 [95% confidence interval: 0.66-1.32]). Compared with the Doc/Carb group, fewer patients in the Pem/Carb group experienced grade 3/4 drug-related, treatment-emergent neutropenia, leukopenia, or febrile neutropenia, and more patients experienced anemia and thrombocytopenia. There were three study drug-related deaths during treatment in each group.
The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced, nonsquamous non-small cell lung cancer.
本研究比较了一线培美曲塞/卡铂或多西他赛/卡铂治疗晚期非鳞状非小细胞肺癌患者的无毒性生存情况。
这项多中心、开放性、平行组、3 期临床试验纳入了随机（1:1）接受培美曲塞/卡铂（n=128）或多西他赛/卡铂（n=132）治疗的患者。患者在每个 21 天周期的第 1 天接受治疗（最多 6 个周期）。治疗包括卡铂（曲线下面积=5mg/ml×min）和培美曲塞（500mg/m2）或多西他赛（75mg/m2）。主要终点为无治疗相关 3/4 级毒性的生存时间，定义为自随机分组至首次治疗相关 3/4 级不良事件或死亡的时间，采用对数秩检验进行分析。分析人群包括培美曲塞/卡铂（培美曲塞/卡铂）组 106 例患者和多西他赛/卡铂（多西他赛/卡铂）组 105 例患者。
与多西他赛/卡铂组相比，培美曲塞/卡铂组无治疗相关 3/4 级毒性的生存时间显著延长（对数秩检验，p<0.001；无治疗相关 3/4 级毒性的中位生存时间：3.2 个月 vs 0.7 个月；调整后的危险比=0.45[95%置信区间：0.34-0.61]）。培美曲塞/卡铂组和多西他赛/卡铂组的总生存时间相似（对数秩检验，p=0.934；中位生存时间：14.9 个月 vs 14.7 个月；调整后的危险比=0.93[95%置信区间：0.66-1.32]）。与多西他赛/卡铂组相比，培美曲塞/卡铂组发生 3/4 级药物相关、治疗相关中性粒细胞减少症、白细胞减少症或发热性中性粒细胞减少症的患者较少，发生贫血和血小板减少症的患者较多。两组各有 3 例研究药物相关死亡。
培美曲塞/卡铂具有良好的获益风险比，提示培美曲塞/卡铂是化疗初治的晚期非鳞状非小细胞肺癌患者的一种合适的一线治疗选择。
