Randomized phase III trial comparing bexarotene (L106949)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I
Randomized phase III trial comparing bexarotene (L106949)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I
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DOI：
10.1200/jco.2007.12.2614
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发表时间：
2008-04-10
影响因子：
45.3
通讯作者：
Dziewanowska, Zofia E.
中科院分区：
文献类型：
--
作者：
Ramlau, Rodryg;Zatloukal, Petr;Dziewanowska, Zofia E.
本研究评估了合成类瑞昔诺贝沙罗汀与一线顺铂/长春瑞滨联合治疗是否能为晚期非小细胞肺癌（NSCLC）患者提供额外的生存益处。患者和方法IIIB期胸腔积液或IV期NSCLC患者和东部肿瘤协作组体能状态为0至1的患者随机分配至开放标签贝沙罗汀400 mg/m2/d组。d与顺铂/长春瑞滨或顺铂/长春瑞滨单独给药。贝沙罗汀组在第1天或之前开始使用抗血脂药物。主要疗效终点是总生存期。主要，次要和支持性疗效analysisweredcovered.ResultsA共623例（312对照，311贝沙罗汀）。总体而言，两个治疗组之间的生存率无显著差异。然而，一项计划外的回顾性分析显示，与对照组患者相比，发生国家癌症研究所3/4级高甘油三酯血症的贝沙罗汀患者亚群（n = 98/306）的中位生存期更长（12.3 v9.9个月;对数秩P = 0.08）。在该亚组中，受益最大的包括男性、吸烟者、IV期疾病患者以及6个月前体重减轻5%或以上的患者。除了白细胞减少症（化疗组较高）和高血压、甲状腺功能减退、呼吸困难和头痛（化疗/贝沙罗汀组较高）外，两组之间3/4级不良事件的发生率、类型和严重程度相当。然而，贝沙罗汀治疗的一个亚组（32%）发生高度高甘油三酯血症的患者似乎比对照组有更好的生存期（12.3个月）;因此甘油三酯反应可能是贝沙罗汀生存获益的生物标志物。
PurposeThis study evaluated whether the combination of the synthetic rexinoid bexarotene with first-line cisplatin/vinorelbine therapy provides additional survival benefit in patients with advanced non small-cell lung cancer (NSCLC).Patients and MethodsPatients with stage IIIB with pleural effusion or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to open-label bexarotene 400 mg/m(2)/d with cisplatin/vinorelbine or to cisplatin/vinorelbine alone. Antilipid agents were initiated on or before day 1 in the bexarotene arm. Primary efficacy end point was overall survival. Primary, secondary and supportive efficacy analyses were conducted.ResultsA total of 623 patients (312 control, 311 bexarotene) were enrolled. Overall, no significant difference in survival occurred between the two treatment groups. However, an unplanned retrospective analysis showed that a subpopulation of bexarotene patients (n = 98 of 306) who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had longer median survival compared with control patients (12.3 v 9.9 months; log-rank P = .08). Within that subgroup, those who benefited the most included males, smokers, those with stage IV disease, and those with a 6-month prior weight loss of 5% or more. Incidence, type and severity of grade 3/4 adverse events were comparable between arms, except for leukopenia (higher in chemotherapy arm) and hyperlipemia, hypothyroidism, dyspnea, and headache (higher in chemotherapy/bexarotene arm).ConclusionThe addition of bexarotene to first-line chemotherapy did not increase survival in patients with advanced NSCLC. However, a subgroup (32%) of bexarotene-treated patients developing high-grade hypertriglyceridemia appeared to have better survival (12.3 months) than controls; thus triglyceride response may be a biomarker of survival benefit with bexarotene.