Gemcitabine, ifosfamide and Navelbine (GIN): a platinum-free combination in advanced non-small-cell lung cancer...

To evaluate the activity and toxicity of gemcitabine, ifosfamide and Navelbine (GIN) in advanced NSCLC.

Stage IIIB/IV NSCLC, WHO performance status <2 and bidimensionally measurable disease were required to enter the study. Gemcitabine 1000 mg/m(2) day 1 and 1000 or 800 mg/m(2) day 4, ifosfamide 3 g/m(2) day 1 (with mesna), Navelbine 25 mg/m(2) day 1 and 25-20 mg/m(2) day 4 were administered on an outpatient basis every 3 weeks for a maximum of six courses. Objective remissions (ORs) were evaluated every two courses. According to Simon's optimal two-stage design, more than 18 ORs out of 54 patients were required to establish the activity of this regimen.

The study group comprised 50 patients. Most patients had metastatic disease (79%) and nonsquamous histology (71%). The total number of courses administered was 200, with a median per patient of 4 (range 1-6). Myelosuppression, in particular leukopenia, was the most frequent toxicity: grade 3-4 neutropenia (WHO) occurred in 47% of the courses, while grade 3-4 thrombocytopenia and anemia affected, respectively, 6.6% and 3.5% of the courses only. Twelve episodes of febrile neutropenia were recorded, and three patients required hospital admission. No toxic deaths were reported. Nonhematological toxicity was generally mild and not clinically relevant. A total of 25 ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI 37.4-66.5%). One-year survival was 46.5%.

The GIN combination showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose limiting. This non-platinum-based triplet may be a valuable alternative to standard platinum-containing regimens and it is under evaluation in an ongoing randomized trial.