title: Phase I study of vinorelbine and carboplatin in advanced non-small cell lung cancer.
abstract: Thirty-one patients with previously untreated advanced non-small cell lung cancer were included in a Phase I study to determine the optimal dose of Carboplatin (CBDCA) which preserves the best Navelbine (NVB) dose-intensity. NVB was administered at a 30-mg/m2 fixed-dose on days 1-8/q 3 weeks, whereas CBDCA doses were planned to be escalated from 275 to 400 mg/m2 on day 1/q 3 weeks for six successive groups of patients. The toxicity limiting dose of CBDCA in the combination was 350 mg/m2 on day 1/q 3 weeks because of repetitive Grade IV neutropenia, and the optimal dose of CBDCA was 325 mg/m2 on day 1/q3 weeks, offering a 86.4% NVB and a 92.6% CBDCA relative dose-intensity for the first 9 weeks. Responses were observed at each step. This study demonstrates the feasibility and the efficacy of the NVB-CBDCA combination. It suggests that dose-intensity calculation can be helpful to determine the recommended dose for Phase II studies of new drug combinations.
authors.affiliation: Chest Disease Department, Saint-Jacques Hospital, Besançon, France.
authors.forename: P
authors.initials: P
authors.lastname: Jacoulet
authors.forename: J L
authors.initials: JL
authors.lastname: Breton
authors.forename: V
authors.initials: V
authors.lastname: Westeel
authors.forename: M
authors.initials: M
authors.lastname: Mercier
authors.forename: G
authors.initials: G
authors.lastname: Garnier
authors.forename: A
authors.initials: A
authors.lastname: Depierre
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine