A dose-escalating study of carboplatin combined with vinorelbine in non-small-cell lung cancer.
Platinum compounds and vinorelbine have been demonstrated to be active in non-small-cell lung cancer (NSCLC). The aims of the study were to assess tolerability and feasibility of increasing doses of carboplatin (level 1: 300 mg/ m2 on day 1, level 2: 350 mg/m2 on day 1, level 3: 400 mg/m2 on day 1) in combination with a fixed dose of vinorelbine (25 mg/m2 on days 1 and 8) in advanced NSCLC. Forty-two patients entered the study and were evaluable for toxicity and response. The patients were not treated using systemic chemotherapy, had TNM stage IIIB-IV, performance status ECOG 0-2, and their median age was 62 (range 41-70) years. The number of patients evaluable for each dose level was 14. A total of 138 (median 3) courses was administered. Nonhematologic side effects included grade I-II mucositis (9%), neurotoxicity (6%), and infections (4%). Myelotoxicity was manageable and generally of short duration, with 19% of the patients having grade III-IV neutropenia. No significant difference was observed for the three treatment groups. No drug-related death was observed. An objective remission was observed in 10 patients (24% response rate; 95% confidence interval 12-39%), with 5 responses in 14 patients treated with the 400-mg/m2 dose. In conclusion, the combination of carboplatin at a dose of 400 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on days 1 and 8 can be safely administered as first-line cytotoxic therapy in advanced NSCLC and warrants further evaluation.
Colleoni
M
M
Division of Medical Oncology, City Hospital, Castelfranco Veneto, Italy.
Boni
L
L
Vicario
G
G
Pancheri
F
F
Sgarbossa
G
G
Nelli
P
P
Calabrò
F
F
Toniolo
L
L
Bortolotti
L
L
Manente
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; 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
D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine