University of Turin, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole 10, 10043 Torino, Italy.
J Clin Oncol. 2012 Jan 10;30(2):172-8. doi: 10.1200/JCO.2010.33.7089. Epub 2011 Nov 28.
This study aimed to determine whether three preoperative cycles of gemcitabine plus cisplatin followed by radical surgery provides a reduction in the risk of progression compared with surgery alone in patients with stages IB to IIIA non-small-cell lung cancer (NSCLC).
Patients with chemotherapy-naive NSCLC (stages IB, II, or IIIA) were randomly assigned to receive either three cycles of gemcitabine 1,250 mg/m(2) days 1 and 8 every 3 weeks plus cisplatin 75 mg/m(2) day 1 every 3 weeks followed by surgery, or surgery alone. Randomization was stratified by center and disease stage (IB/IIA v IIB/IIIA). The primary end point was progression-free survival (PFS). Results The study was prematurely closed after the random assignment of 270 patients: 129 to chemotherapy plus surgery and 141 to surgery alone. Median age was 61.8 years and 83.3% were male. Slightly more patients in the surgery alone arm had disease stage IB/IIA (55.3% v 48.8%). The chemotherapy response rate was 35.4%. The hazard ratios for PFS and overall survival were 0.70 (95% CI, 0.50 to 0.97; P = .003) and 0.63 (95% CI, 0.43 to 0.92; P = .02), respectively, both in favor of chemotherapy plus surgery. A statistically significant impact of preoperative chemotherapy on outcomes was observed in the stage IIB/IIIA subgroup (3-year PFS rate: 36.1% v 55.4%; P = .002). The most common grade 3 or 4 chemotherapy-related adverse events were neutropenia and thrombocytopenia. No treatment-by-histology interaction effect was apparent.
Although the study was terminated early, preoperative gemcitabine plus cisplatin followed by radical surgery improved survival in patients with clinical stage IIB/IIIA NSCLC.
本研究旨在确定对于临床分期为 IIB/IIIA 期的非小细胞肺癌（NSCLC）患者，与单纯手术相比，吉西他滨加顺铂术前 3 个周期治疗后行根治性手术是否能降低进展风险。
将未经化疗的 NSCLC（IB 期、II 期或 IIIA 期）患者随机分配，接受每 3 周 1 天和 8 天给予 1250mg/m2 的吉西他滨联合 75mg/m2 的顺铂（每 3 周 1 天）治疗 3 个周期，随后行手术治疗，或单纯手术治疗。随机分组按中心和疾病分期（IB/IIA 期与 IIB/IIIA 期）分层。主要终点为无进展生存期（PFS）。
在随机分配 270 例患者后，该研究提前关闭：129 例患者接受化疗加手术，141 例患者接受单纯手术。中位年龄为 61.8 岁，83.3%为男性。单纯手术组疾病分期 IB/IIA 期的患者略多（55.3%比 48.8%）。化疗的客观缓解率为 35.4%。PFS 和总生存期的风险比分别为 0.70（95%CI，0.50 至 0.97；P=0.003）和 0.63（95%CI，0.43 至 0.92；P=0.02），均有利于化疗加手术。术前化疗对 IIB/IIIA 亚组患者的结局有显著影响（3 年 PFS 率：36.1%比 55.4%；P=0.002）。最常见的 3 级或 4 级化疗相关不良事件为中性粒细胞减少和血小板减少。未观察到治疗与组织学之间存在交互作用。
尽管该研究提前终止，但吉西他滨加顺铂术前治疗后行根治性手术可改善临床分期为 IIB/IIIA 期 NSCLC 患者的生存。
