Journal of Clinical Oncology, Vol 18, Issue 7
(April), 2000: 1451-1457
© 2000 American Society for Clinical Oncology
Randomized Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine With Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer: Interim Analysis of a Phase III Trial of the Southern Italy Cooperative Oncology Group
By Pasquale Comella,
Giuseppe Frasci,
Nicola Panza,
Luigi Manzione,
Giuseppe De Cataldis,
Riccardo Cioffi,
Luigi Maiorino,
Enrico Micillo,
Vito Lorusso,
Gaetano Di Rienzo,
Gianfranco Filippelli,
Alfredo Lamberti,
Michele Natale,
Domenico Bilancia,
Gianpaolo Nicolella,
Angelo Di Nota,
Giuseppe Comella
From the Division of Medical Oncology A, National Tumor Institute; Divisions of Medical Oncology and Pneumology, Cardarelli Hospital; Division of Medical Oncology, San Gennaro Hospital; Chair of Respiratory Diseases, Second University School of Medicine; Division of Pneumology, Monaldi Hospital, Naples; Division of Medical Oncology, San Carlo Hospital, Potenza; Division of Medical Oncology, Da Procida Hospital, Salerno; Division of Pneumology, City Hospital, Caserta; Division of Medical Oncology, Oncologic Institute; Division of Thoracic Surgery, San Paolo Hospital, Bari; Division of Medical Oncology, Oncologic Hospital, Palermo, Italy.
Address reprint requests to Pasquale Comella, MD, Division of Medical Oncology A, National Tumor Institute, via M. Semmola 80131, Naples, Italy; email pcomella{at}sirio-oncology.it
PURPOSE: 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).
PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of  70 years, and an Eastern Cooperative Oncology Group performance status 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m2, gemcitabine 1,000 mg/m2, and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m2 on days 1 and 29 and vinorelbine 30 mg/m2/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.
RESULTS: 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.
CONCLUSION: 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.
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