Gemcitabine, ifosfamide and vinorelbine in advanced non-small cell lung cancer: a phase II study.

Background: The objective of this phase II study was to determine the activity and toxicity of gemcitabine, ifosfamide and vinorelbine, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: Chemotherapy-naive patients with unresectable, stage IIIB and stage IV NSCLC, measurable lesions and an Eastern Co-operative Oncology Group (ECOG) performance status ≤3, were entered into the trial. The treatment consisted of ifosfamide 1500 mg/m 2 on days 1 to 3 with vinorelbine 25 mg/m 2 and gemcitabine 1000 mg/m 2 on days 3 and 8, every 3 weeks. Results: Fifty-four patients with stage IIIB (24%) and stage IV (76%) were enrolled into the trial. The median age of the patients was 65 years. The performance status was 0-1, 2 and 3 in 48%, 43% and 9% of patients, respectively. The histology was mainly squamous cell carcinoma (52%), which was poorly-differentiated in 30% of patients. All patients, receiving a total of 249 chemotherapy courses, were assessable for response and toxicity on an intent-to-treat basis. Objective responses included complete response in 3 (5.6%) patients (95% CI: 1.1% to 15.3%), partial response in 26 (48.1%) patients (95% CI: 34.3% to 62.2%), giving an overall response rate of 53.7% (95% CI: 39.6% to 67.4%). Stable disease was observed in 20 (37%) patients (95% Cl: 24.3% to 51.2%) and progressive disease in 5 (9.3%) patients (95% CI: 3% to 20.3%). The median time to progression was 8.8 months (range: 2-55+ months). The median overall survival was 13.2 months (range: 2-55+). The 1-year survival rate was 56% for all patients, comprising 78% and 47% for stage IIIB and stage IV patients, respectively (p=0.088). Myelosuppression was the main side-effect with (WHO) grade 3/4 neutropenia and thrombocytopenia in 56% and 13% of the patients, respectively. Conclusion: Our results showed that even patients with a poor performance status may benefit from gemcitabine, ifosfamide and vinorelbine treatment, with acceptable toxicity.