Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G
Division of Medical Oncology A, National Tumor Institute, Naples, Italy.
J Clin Oncol. 2000 Apr;18(7):1451-7. doi: 10.1200/JCO.2000.18.7.1451.
In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG).
From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival.
The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen.
The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.
在我们之前的II期研究中，顺铂、吉西他滨和长春瑞滨（PGV）方案使晚期非小细胞肺癌（NSCLC）患者的中位生存时间（MST）达到约1年。本研究旨在比较接受该三联方案治疗的患者的MST与接受顺铂和长春瑞滨（PV）或顺铂和吉西他滨（PG）治疗的患者的MST。
从1997年4月起，将年龄≤70岁、东部肿瘤协作组体能状态≤1的局部晚期或转移性NSCLC患者随机分为以下方案之一：每3周的第1天和第8天给予顺铂50mg/m²、吉西他滨1000mg/m²和长春瑞滨25mg/m²（A组）；每4周的第1天给予顺铂100mg/m²，第1、8和15天给予吉西他滨1000mg/m²（B组）；或第1天和第29天给予顺铂120mg/m²，每周给予长春瑞滨30mg/m²（C组）。根据III期试验的两阶段设计，计划在每组的前60例患者可评估生存情况时进行中期分析。
1999年4月分析了180例NSCLC患者（IIIB期76例；IV期104例）的生存数据。总体上，128例患者死亡（PGV组33例；PG组42例；PV组53例）。PGV组、PG组和PV组患者的MST分别为51周、42周和35周，相应的1年预计生存率分别为45%、40%和34%。仅考虑IV期疾病患者时，PGV组（MST = 47周）与PG组（34周）和PV组（27周）之间的差异更为明显。在多变量Cox分析中，接受PGV治疗的患者与接受PV治疗的患者相比，估计死亡风险为0.35（95%置信区间，0.16至0.77；P <.01）。PGV组的缓解率为47%，PG组为30%，PV组为25%。接受PGV方案的患者血液学和非血液学毒性均未显著更差。
与PV联合方案相比，PGV方案可显著提高生存率（MST长3个月以上）。由于生存差异符合早期终止规则之一，PV组的入组已停止（原假设被拒绝）。PGV组和PG组仍在继续入组，以确定PGV方案是否也能产生比PG方案显著更长的生存期。
