Edelman Martin J, Clark Joseph I, Chansky Kari, Albain Kathy, Bhoopalam Nirmala, Weiss Geoffrey R, Giguere Jeffrey K, Kelly Karen, Crowley John, Gandara David R
University of Maryland Greenebaum Cancer Center, Baltimore, Maryland, USA.
Clin Cancer Res. 2004 Aug 1;10(15):5022-6. doi: 10.1158/1078-0432.CCR-04-0002.
Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC.
Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0-1 and normal organ function were eligible.
arm 1, carboplatin (area under the curve = 5.5 mg/ml x min day 1) and gemcitabine (1000 mg/m(2) days 1 and 8 every 21 days x 3) followed by paclitaxel (225 mg/m(2) every 21 days x 3) or arm 2, cisplatin (100 mg/m(2) day 1), vinorelbine (25 mg/m(2) days 1 and 8 every 21 d x 3) followed by docetaxel (75-100 mg/m(2) every 21 days x 3).
Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively.
Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.
提高非小细胞肺癌(NSCLC)的化疗疗效需要研发新药或新策略,以便更好地使用现有药物。序贯给药提供了增加药物多样性同时维持剂量强度的机会。基于紫杉烷作为二线治疗的活性数据以及超过三个周期铂类治疗缺乏疗效的数据,这项随机II期研究测试了晚期NSCLC中计划序贯化疗的概念。
入选标准为IIIb期(胸腔积液)/IV期NSCLC患者,体能状态为0 - 1且器官功能正常。
第1组,卡铂(曲线下面积 = 5.5 mg/ml×分钟,第1天)和吉西他滨(1000 mg/m²,第1天和第8天,每21天重复×3次),随后给予紫杉醇(225 mg/m²,每21天重复×3次);或第2组,顺铂(100 mg/m²,第1天)、长春瑞滨(25 mg/m²,第1天和第8天,每21天重复×3次),随后给予多西他赛(75 - 100 mg/m²,每21天重复×3次)。
共纳入204例患者,其中178例符合条件且可评估。第1组80%的患者为IV期,第2组为85%。第1组和第2组的缓解率分别为21%和28%。第1组和第2组的中位生存期、1年生存率和2年生存率分别为9个月、34%和13%,以及9个月、36%和8%。
本研究中使用的序贯疗法与先前西南肿瘤协作组在该人群中进行的两种药物联合试验的疗效相当;然而,它未达到进一步研究的标准。