Hanna Nasser, Neubauer Marcus, Yiannoutsos Constantin, McGarry Ronald, Arseneau James, Ansari Rafat, Reynolds Craig, Govindan Ramaswamy, Melnyk Anton, Fisher William, Richards Donald, Bruetman Daniel, Anderson Thomas, Chowhan Naveed, Nattam Sreenivasa, Mantravadi Prasad, Johnson Cynthia, Breen Tim, White Angela, Einhorn Lawrence
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.
J Clin Oncol. 2008 Dec 10;26(35):5755-60. doi: 10.1200/JCO.2008.17.7840. Epub 2008 Nov 10.
Concurrent chemoradiotherapy is standard treatment for patients with inoperable stage III non-small-cell lung cancer (NSCLC). A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin (P), etoposide (E), and radiation (XRT) resulted in a median survival time (MST) of 26 months. This randomized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival.
Eligible patients had stage IIIA or IIIB NSCLC, baseline performance status of 0 to 1, forced expiratory volume in 1 second >or= 1 L, and less than 5% weight loss. Patients received P 50 mg/m(2) intravenously (IV) on days 1, 8, 29, and 36 and E 50 mg/m(2) IV on days 1-5 and 29-33 concurrently with chest XRT to 59.40 Gy. Patients who did not experience progression were randomly assigned to docetaxel 75 mg/m(2) IV every 21 days for three cycles versus observation. The primary end point was to compare overall survival (Kaplan-Meier analysis).
On the basis of evidence of futility, a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients. Patient characteristics (n = 203) were as follows: 34% female; median age, 63 years; 39.4% stage IIIA; and 60.6% stage IIIB. One hundred forty-seven (72.4%) of 203 patients were randomly assigned to docetaxel (n = 73) or observation (n = 74). Grade 3 to 5 toxicities during docetaxel included febrile neutropenia (10.9%) and pneumonitis (9.6%); 28.8% of patients were hospitalized during docetaxel (v 8.1% in observation arm), and 5.5% died as a result of docetaxel. The MST for all patients (n = 203) was 21.7 months; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm (P = .883).
Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC.
同步放化疗是不可切除的Ⅲ期非小细胞肺癌（NSCLC）患者的标准治疗方法。西南肿瘤协作组进行的一项Ⅱ期研究，在顺铂（P）、依托泊苷（E）和放疗（XRT）后使用多西他赛巩固治疗，中位生存时间（MST）为26个月。这项随机Ⅲ期试验评估了多西他赛巩固治疗是否是生存改善的原因。
符合条件的患者患有ⅢA或ⅢB期NSCLC，基线体能状态为0至1，第1秒用力呼气量≥1L，体重减轻少于5%。患者在第1、8、29和36天静脉注射（IV）顺铂50mg/m²，在第1 - 5天和29 - 33天静脉注射依托泊苷50mg/m²，同时胸部XRT至59.40Gy。未出现疾病进展的患者被随机分配接受每21天静脉注射多西他赛75mg/m²，共三个周期，或接受观察。主要终点是比较总生存期（Kaplan - Meier分析）。
基于无效证据，数据与安全监测委员会在分析了最初203例患者后建议提前终止试验。患者特征（n = 203）如下：女性占34%；中位年龄63岁；ⅢA期占39.4%；ⅢB期占60.6%。203例患者中的147例（72.4%）被随机分配接受多西他赛治疗（n = 73）或观察（n = 74）。多西他赛治疗期间3至5级毒性包括发热性中性粒细胞减少（10.9%）和肺炎（9.6%）；28.8%的患者在多西他赛治疗期间住院（观察组为8.1%），5.5%的患者因多西他赛治疗死亡。所有患者（n = 203）的MST为21.7个月；多西他赛组的MST为21.2个月，观察组为23.2个月（P = 0.883）。
在PE/XRT后进行多西他赛巩固治疗会增加毒性，但与单纯PE/XRT相比，对于不可切除的Ⅲ期NSCLC患者，并未进一步改善生存期。
