Pujol Jean Louis, Breton Jean Luc, Gervais Radj, Tanguy Marie-Laure, Quoix Elisabeth, David Philippe, Janicot Henri, Westeel Virginie, Gameroff Sabine, Genève Jean, Maraninchi Dominique
Centre Hospitalier Universitaire, Montpellier Cedex 5, France.
J Clin Oncol. 2007 Sep 1;25(25):3945-51. doi: 10.1200/JCO.2007.11.8109.
This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer (SCLC).
One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4'-epidoxorubicin (PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide (400 mg daily) or placebo.
After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo (n = 43) or thalidomide (n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant (minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log-rank test: hazard ratio [HR] = 0.74; 95% CI, 0.49 to 1.12; P = .16). Patients with a performance status (PS) of 1 or 2 who received thalidomide had a significantly longer survival (HR = 0.59; 95% CI, 0.37 to 0.92; P = .02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide (HR = 0.54; 95% CI, 0.36 to 0.87; P = .02), whereas the difference did not reach statistical significance for the whole population (HR = 0.74; 95% CI, 0.49 to 1.12; P = .15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group (33% v 12%, respectively).
Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 (exploratory analyses), deserving further studies targeting angiogenesis in this disease.
本随机、双盲、安慰剂对照的III期研究旨在确定沙利度胺是否能延长广泛期小细胞肺癌（SCLC）患者的生存期。
119例患者接受了两个疗程的依托泊苷、顺铂、环磷酰胺和表柔比星（PCDE）治疗。从化疗毒性中恢复的缓解患者被随机分配接受另外四个PCDE疗程加沙利度胺（每日400mg）或安慰剂治疗。
在前两个PCDE疗程后，客观缓解率为81.5%，92例患者被随机分配接受安慰剂（n = 43）或沙利度胺（n = 49）治疗。安慰剂组的中位暴露持续时间为4.5个月，沙利度胺组为4.9个月。与接受安慰剂的患者相比，接受沙利度胺治疗的患者生存期更长，尽管差异无统计学意义（最短随访3年；中位生存时间分别为11.7个月和8.7个月；对数秩检验：风险比[HR]=0.74；95%CI，0.49至1.12；P = 0.16）。体能状态（PS）为1或2且接受沙利度胺治疗的患者生存期显著更长（HR = 0.59；95%CI，0.37至0.92；P = 0.02）。PS为1或2且接受沙利度胺治疗的患者疾病进展也较慢（HR = 0.54；95%CI，0.36至0.87；P = 0.02），而在总体人群中差异未达到统计学意义（HR = 0.74；95%CI，0.49至1.12；P = 0.15）。与安慰剂组相比，沙利度胺组神经病变的发生率更高（分别为33%和12%）。
沙利度胺治疗与SCLC患者生存期的显著改善无关。患者组间生存结果存在明显异质性。在PS为1或2的患者中观察到了一些益处（探索性分析），值得针对该疾病的血管生成进行进一步研究。
