Sweeney C J, Zhu J, Sandler A B, Schiller J, Belani C P, Langer C, Krook J, Harrington D, Johnson D H
Department of Medicine, Division of Hematology/Oncology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Cancer. 2001 Nov 15;92(10):2639-47. doi: 10.1002/1097-0142(20011115)92:10<2639::aid-cncr1617>3.0.co;2-8.
Eastern Cooperative Oncology Group (ECOG) Study E1594 compared paclitaxel and cisplatin with three newer chemotherapy doublets in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). The accrual of patients with an ECOG performance status (PS) of 2 was discontinued due to a perceived rate of unacceptable toxicity.
Patients were stratified by PS and randomized to one of the following treatments: 1) paclitaxel (135 mg/m2) over 24 hours with cisplatin (75 mg/m2) on a 21-day cycle; 2) cisplatin (100 mg/m2) with gemcitabine (1 g/m2) on Days 1, 8, and 15 on a 28-day cycle; 3) cisplatin (75 mg/m2) with docetaxel (75 mg/m2) on a 21-day cycle; and 4) paclitaxel (225 mg/m2) over 3 hours with carboplatin (area under the curve, 6). All tests of statistical significance were two-sided.
Sixty-eight patients with an ECOG PS of 2 were enrolled, and 64 patients were evaluable for toxicity and response. Fifty-six percent of 64 evaluable patients were male, and 81% had Stage IV disease. Grade 3-4 hematologic toxicities occurred in > 50% of the patients in each treatment group. Nonhematologic Grade 3-4 toxicities occurred significantly less often in the paclitaxel and carboplatin arm (P = 0.0032). The overall rate of toxicity did not differ significantly from the rate of toxicity in the PS-0 or PS-1 cohorts. There were 5 deaths (7.35%) among 68 patients with a PS of 2 during therapy; however, only 2 of those deaths were attributed to therapy. The overall response rate for the 64 evaluable patients was 14%. The overall median survival of all 68 patients with a PS of 2, as determined by an intent-to-treat analysis, was 4.1 months.
Patients with advanced NSCLC and a PS of 2 experienced a large number of adverse reactions and overall poor survival. A comparison with patients with a PS of 0-1 suggests that these events and the shorter survival were related to disease process rather than treatment. Alternative strategies need to be explored with therapy specifically tailored for this group of patients.
东部肿瘤协作组（ECOG）的E1594研究比较了紫杉醇和顺铂与三种新型化疗方案在晚期非小细胞肺癌（NSCLC）患者治疗中的效果。由于预期的不可接受毒性发生率，ECOG体能状态（PS）评分为2的患者入组被终止。
患者按PS分层，随机分配至以下治疗方案之一：1）24小时内给予紫杉醇（135mg/m²），每21天周期第1天给予顺铂（75mg/m²）；2）第1、8和15天给予顺铂（100mg/m²）与吉西他滨（1g/m²），每28天为一个周期；3）每21天周期给予顺铂（75mg/m²）与多西他赛（75mg/m²）；4）3小时内给予紫杉醇（225mg/m²）与卡铂（曲线下面积为6）。所有统计学显著性检验均为双侧检验。
纳入68例ECOG PS评分为2的患者，64例患者可评估毒性和疗效。64例可评估患者中56%为男性，81%为IV期疾病。每个治疗组中超过50%的患者发生3-4级血液学毒性。紫杉醇和卡铂组3-4级非血液学毒性发生率显著较低（P = 0.0032）。总体毒性发生率与PS为0或PS为1的队列中的毒性发生率无显著差异。68例PS为2的患者在治疗期间有5例死亡（7.35%）；然而，这些死亡中只有2例归因于治疗。64例可评估患者的总体缓解率为14%。通过意向性分析确定，所有68例PS为2的患者的总体中位生存期为4.1个月。
晚期NSCLC且PS为2的患者经历了大量不良反应且总体生存期较差。与PS为0-1的患者比较表明，这些事件和较短生存期与疾病进程而非治疗有关。需要探索针对该组患者量身定制治疗方案的替代策略。
