Vinorelbine (Navelbine)/carboplatin combination therapy: dose intensification with granulocyte colony-stimulating factor.

Treatment with platinum agents or the new vinca alkaloid vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) results in prolonged survival in patients with advanced non-small cell lung cancer (NSCLC). To determine whether a unique combination of these agents might enhance activity against NSCLC, a combination chemotherapy regimen consisting of intravenous carboplatin, administered on days 1 and 29, and intravenous vinorelbine, given once weekly, was evaluated. Because the dose-limiting toxicity of both agents is myelosuppression, an additional study goal was to assess the ability of granulocyte colony-stimulating factor to alleviate hematologic toxicity and allow on-time, full-dose vinorelbine therapy. To this end, a phase I/II study was begun. Phase I of the study included 22 patients (15 men and seven women) with a median age of 63 years (age range, 39 to 77 years) who had stage IV NSCLC and no prior chemotherapy. Phase I consisted of 28-day cycles in which intravenous carboplatin was administered at an area under the curve of 7 by the Calvert formula, dose range 350 to 450 mg/m2, and intravenous vinorelbine was administered weekly. Granulocyte colony-stimulating factor was administered if dose-limiting neutropenia developed. Four cohorts of patients were studied, ranging from those who received no vinorelbine to those who received drug doses of up to 30 mg/m2. Patients were able to tolerate the highest dose of vinorelbine, but the majority required granulocyte colony-stimulating factor support to do so. No novel toxicities were observed in patients treated with the combination of carboplatin and vinorelbine.(ABSTRACT TRUNCATED AT 250 WORDS)