GLOB-1: A prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients

Abstract

Background: The standard doublet, vinorelbine-cisplatin, was compared with a triplet of vinorelbine-ifosfamide-cisplatin, in terms of survival, in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: From February 1998 to June 1999, 259 chemonaïve patients entered the study and were randomised to receive either vinorelbine-cisplatin (NP; vinorelbine 30 mg/m2 on days 1, 8 and 15 with cisplatin 80 mg/m2 on day 1) or vinorelbine-ifosfamide-cisplatin (NIP; vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 g/m2 on day 1 and cisplatin 75 mg/m2 on day 1), with both regimens being repeated every 3 weeks. All patients had stage IV or relapsed disease and a performance score of 0 or 1. Results: The overall response rate was 34.6% for NP and 35.7% for NIP. Median and 1-year survival rates were 10.0 months and 38.4% for NP, and 8.2 months and 33.7% for NIP, respectively. A median of four cycles was administered in each arm. The major World Health Organization grade 3-4 toxicities for NP and NIP, respectively, were: neutropenia (20.3% compared with 9% of cycles), anaemia (4. 1 % compared with 5% of cycles), nausea and vomiting (22.2% compared with 19.4% of patients) and alopecia (5.6% compared with 29.8% of patients). Four toxic deaths occurred in the NP arm and eight in the NIP arm. Conclusions: The different schedules of vinorelbine in the two arms led to a greater survival in the NP arm without impairing the tolerance profile, although this is not statistically significant. This confirms that the two-drug combination NP is a reference treatment for metastatic NSCLC. The role of three-drug combinations remains questionable in this subset of patients.