A randomized phase II trial of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin in the treatment of chemo-naive patients with stages III and IV non-small cell lung cancer (NSCLC).

BACKGROUND: Third-generation platinum-based combinations are established as first-line treatment for advanced non-small cell lung cancer (NSCLC). Non-platinum regimens could be an alternative if they show similar efficacy with better tolerability. This randomized phase II trial compared the objective tumor response rate (ORR) of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin. Secondary objectives included time to disease progression (TTP), overall survival and toxicity.

METHODS: Chemo-naive patients with stages III and IV NSCLC and Karnofsky performance status >70 were assigned to receive either (a) gemcitabine 1000mg/m(2) plus vinorelbine 25mg/m(2) on days 1 and 8 for 2 cycles, followed by gemcitabine 1000mg/m(2) on days 1 and 8 plus ifosfamide 2000mg/m(2) on day 1 (GV-GI arm) for 2 cycles or (b) gemcitabine 1250mg/m(2) on days 1 and 8 with cisplatin 70mg/m(2) on day 1 (GC arm) for 4 cycles.

RESULTS: Between July 2001 and January 2003, 102 patients were enrolled (50 on the GV-GI arm and 52 on the GC arm). Patient characteristics were balanced between arms (GV-GI arm: median age 59 years, 84% male, 22 stage IIIB, 24 stage IV, 4 stage IIIA; GC arm: median age 56 years, 87% male, 27 stage IIIB, 23 stage IV, 2 stage IIIA). Of the 101 patients evaluable for response, ORR was significantly higher on the GC arm than on the GV-GI arm (25% versus 6%, respectively; p=0.007). No complete responses occurred. TTP was longer on the GC arm than on the GV-GI arm (median 135 and 79 days, respectively), although this difference was not statistically significant (p=0.065). Survival was not significantly different between the arms (median 293 and 197 days, respectively; p=0.16). Although significantly more thrombocytopenia was reported on the GC arm (22% and 4%, respectively; p=0.02), it did not lead to more transfusions (15 transfusions in 5 patients versus 14 transfusions in 6 patients, respectively). There was no significant difference in other safety parameters between treatment arms.

CONCLUSIONS: GC appears to produce better response in advanced NSCLC than GV-GI, with a trend towards longer TTP. Except for more thrombocytopenia with GC, similar toxicity profiles were observed.