Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study.

OBJECTIVE: A phase II study was conducted to evaluate the efficacy and toxicity of vinorelbine-carboplatin (VNB-C) combination as a salvage treatment in patients with advanced non-small cell lung cancer (NSCLC) progressing after or failing previous non-platinum, taxane-based treatment. PATIENTS AND METHODS: Thirty-seven patients with cytologically or histologically confirmed NSCLC were enrolled. VNB 30 mg/m(2) was administered on days 1 and 8 and C 300 mg/m(2) on day 1 every 28 days. G-CSF (5 microg/kg per day s.c.) was used prophylactically on days 10-15 in case of grade 3-4 neutropenia or febrile neutropenia after the first cycle. RESULTS: Twenty-nine patients were evaluable for response and all were evaluable for toxicity. In an intention-to-treat analysis, two (5%) complete and four (11%) partial responses were documented for an overall response rate of 16% (95% CI, 4.49-28.84%). Eleven (30%) patients experienced disease stabilisation and 20 (54%) disease progression. The median duration of response was 7.5 months, the median TTP was 9 months, and the median survival was 8.5 months. Patients with objective remission and stable disease had a statistically significant survival benefit over patients with disease progression. Grade 3 and 4 neutropenia occurred in three (8%) and ten (27%) patients, respectively, and six cases (16%) were complicated with fever. Grade 4 thrombocytopenia was documented in one (3%) patient. Non-hematological toxicity was mild, with grade 2 and 3 asthenia reported in 18 (48%) patients. No treatment-related deaths occurred. CONCLUSION: VNB-C combination is well tolerated and retains a notable degree of activity in NSCLC patients progressing after previous non-platinum, taxane-based treatment. Moreover, it confers tumour growth control in a significant proportion of patients, and this seems to be associated with a survival benefit for them.

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

UNLABELLED: Two parallel phase II trials were conducted in order to evaluate the efficacy and toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carboplatin (VNB-C) combinations as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients failing platinum-based front-line chemotherapy were enrolled in the VNB-IFX trial while 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 with VNB-C [median age: 61 years; PS (WHO) 0--1: 51% and stage IV: 84%]. Patients 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 microg/kg/day s.c.) was administered prophylactically on days 11--16 or until hematological recovery. The VNB-C regimen consisted of carboplatin 300 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 28 days. 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 16% (median duration of response: 7.5 months) for the VNB-C combination. The median time to progression and survival for patients receiving VNB-IFX were 4.5 and 6 months (1-year survival: 19%), respectively; the corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%). The median 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 treated with VNB-IFX; all cases were complicated with fever. Grade 3--4 neutropenia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%) developed neutropenic fever. There were no treatment-related deaths. Non-hematologic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2--3 peripheral 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 of disease was associated with a favorable survival in both studies.