Lau D, Leigh B, Gandara D, Edelman M, Morgan R, Israel V, Lara P, Wilder R, Ryu J, Doroshow J
University of California, Davis Cancer Center, and Veterans Affairs Northern California Health Care System, Sacramento 95817, USA.
J Clin Oncol. 2001 Jan 15;19(2):442-7. doi: 10.1200/JCO.2001.19.2.442.
Recent studies have suggested the superiority of concurrent chemoradiotherapy and the efficacy of paclitaxel/carboplatin in advanced non-small-cell lung cancer (NSCLC). In view of those results, we sought to examine the safety and efficacy of administration of radiosensitizing paclitaxel twice weekly and carboplatin weekly with concurrent thoracic radiation therapy (XRT) followed by consolidation paclitaxel and carboplatin for stage III NSCLC in a multi-institutional phase II trial.
Induction chemoradiotherapy consisted of paclitaxel 30 mg/m2 delivered intravenously (IV) for 1 hour twice weekly for 6 weeks, carboplatin at a dose based on an area under the concentration-time curve (AUC) of 1.5 mg/mL x min, given IV once weekly for 6 weeks, and concomitant XRT of 1.8 to 2.0 Gy daily for a total of 61 Gy. Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min.
Thirty-four patients were eligible. Their median age was 62 years (range, 39 to 73 years), 59% were female, 41% were male, 94% had a performance status of 0 or 1, 38% had stage IIIA NSCLC, and 62% had stage IIIB NSCLC. Common grade III and IV toxicities during the induction chemoradiation phase included esophagitis (38%) and neutropenia (12%). The most common adverse reaction during consolidation chemotherapy was grade III neutropenia in five patients (15%). The overall response rate was 71%, which was achieved in the induction phase. The median follow-up was 20 months, the median survival was 17 months, and 2-year actuarial survival rate was 40% (95% confidence interval, 20% to 65%).
This regimen is tolerable and results are promising. We recommend further evaluation of this regimen in a phase III trial.
近期研究表明同步放化疗具有优越性，且紫杉醇/卡铂对晚期非小细胞肺癌（NSCLC）有效。鉴于这些结果，我们试图在一项多机构II期试验中，研究每周两次给予放疗增敏剂紫杉醇和每周一次给予卡铂并同步进行胸部放疗（XRT），随后给予巩固性紫杉醇和卡铂治疗III期NSCLC的安全性和疗效。
诱导放化疗包括静脉注射（IV）紫杉醇30mg/m²，每周两次，持续1小时，共6周；卡铂剂量基于浓度-时间曲线下面积（AUC）为1.5mg/mL·min，每周静脉注射一次，共6周；同时每天进行1.8至2.0Gy的XRT，总量为61Gy。达到完全缓解、部分缓解或疾病稳定的患者接受两个21天周期的巩固化疗，包括静脉注射紫杉醇200mg/m²，持续3小时，以及卡铂剂量基于AUC为6mg/mL·min。
34例患者符合条件。他们的中位年龄为62岁（范围39至73岁），59%为女性，41%为男性，94%的体能状态为0或1，38%患有IIIA期NSCLC，62%患有IIIB期NSCLC。诱导放化疗阶段常见的III级和IV级毒性包括食管炎（38%）和中性粒细胞减少（12%）。巩固化疗期间最常见的不良反应是5例患者（15%）出现III级中性粒细胞减少。总缓解率为71%，在诱导阶段实现。中位随访时间为20个月，中位生存期为17个月，2年精算生存率为40%（95%置信区间，20%至65%）。
该方案耐受性良好且结果令人鼓舞。我们建议在III期试验中进一步评估该方案。
