Vinorelbine-based regimens as salvage treatment in patients with advanced non-small cell lung cancer: Two parallel multicenter phase II trials

Two parallel phase II trials were conducted in order to evaluate the effica cy and toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carbopl atin (VNB-C) combinations as salvage treatment in patients with advanced no n-small cell lung cancer (NSCLC). Patients and Methods: Patients failing pl atinum-based front-line chemotherapy were enrolled in the VNB-IFX trial whi le patients failing non-platinum-containing chemotherapy were treated with VNB-C. Twenty-nine patients were treated with VNB-IFX [median age: 59 years ; performance status, PS (WHO) 0-1: 72% and disease stage IV: 79%] and 37 w ith VNB-C [median age: 61 years; PS (WHO) 0-1: 51% and stage IV: 84%]. Pati ents received vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and ifosfamide 1. 6 g/m(2) i.v. on days 8-10 with uroprotective mesna, in cycles of 28 days. G-CSF (5 mug/kg/day s.c.) was administered prophylactically on days 11-16 o r until hematological recovery. The VN B-C regimen consisted of carboplatin 300 mg/m2 on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 28 day s. Results: Twenty-six patients were evaluable for response in the VNB-IFX trial and 29 in the VNB-C. Overall response rates (intent-to-treat analysis ) were 3% (1 patient; duration of response: 3 months) for the VNB-IFX and 1 6% (median duration of response: 7.5 months) for the VN B-C combination. Th e median time to progression and survival for patients receiving VNB-IFX we re 4.5 and 6 months (l-year survival: 19%), respectively; the corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%). The media n survival of patients achieving stable disease was 10 (VNB-IFX) and 14.5 ( VNB-C) months. Grade 3-4 neutropenia occurred in 4 (13%) of the patients tr eated with VNB-IFX; all cases were complicated with fever. Grade 3-4 neutro penia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%) devel oped neutropenic fever. There were no treatment-related deaths. Non-hematol ogic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2-3 pe ripheral neurotoxicity occurring in 3 (10%) and 7 (19%) patients, and grade 2-3 asthenia in 11 (38%) and 18 (48%) patients, respectively. Conclusion: Both combinations were associated with a tolerable toxicity profile. VNB-C demonstrated notable activity in patients previously treated with a taxane- based regimen, whilst VNB-IFX failed to produce a significant response rate in patients treated with platinum-containing chemotherapy, Stabilization o f disease was associated with a favorable survival in both studies. Copyrig ht (C) 2001 S.Karger AG,Basel.