Cisplatin and ifosfamide with various doses of vinorelbine (navelbine) in advanced non-small lung cancer.

From November 1992 to March 1994 we concluded a phase II trial of the combination of cisplatin 75 mg/m2 and ifosfamide 3 g/m2 on day 1 and increasing doses of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France). Group A was given vinorelbine 25 mg/m2 on day 1, group B 25 mg/m2 on days 1 and 8, and group C 25 mg/m2 on days 1 and 15 and 12.5 mg/m2 on day 8. Inclusion criteria were histologically proven non-small cell lung cancer, stage IIIB or IV disease, no underlying disease, performance status < 2, no previous chemotherapy or radiotherapy, not older than 75 years, and informed consent. Treatment was given for 3 weeks. Eighty-six patients were included: 34 in group A, 28 in group B, and 24 in group C. One patient in group B was excluded because of false histology on review. Thirty-seven patients had stage IIIB and 48 had state IV disease, and 37 had squamous cell carcinoma, 32 had adenocarcinoma, and 16 had large cell carcinoma. The median age was 59.2 years (age range, 36 to 73 years). Evaluation was made 3 weeks after the third course of therapy. Thoracic radiotherapy (60 Gy) was given in stage IIIB disease; in stage IV disease, when an objective response was achieved, three additional courses of chemotherapy were given. The response rate after three cycles was 32% in group A, 44% in group B, and 67% in group C. Dose intensity, using Hryniuk's method, was the same for cisplatin and ifosfamide in the three groups. Dose intensity for vinorelbine was 8.1 mg/m2/wk in group A, 14.7 mg/m2/wk in group B, and 16.9 mg/m2/wk in group C. This study shows that increased dose intensity with vinorelbine is feasible and seems to increase the response rate and median survival, which was 28 weeks in group A and 38 weeks in group B. Median survival had not been reached in group C.