title: Vinorelbine (Navelbine)/carboplatin combination therapy: dose intensification with granulocyte colony-stimulating factor.
abstract: 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)
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: M A
authors.initials: MA
authors.lastname: O'Rourke
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D012074:Remission Induction; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine