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) d
ose-intensity. NVB was administered at a 30-mg/m(2) fixed-dose on days
1-8/q 3 weeks, whereas CBDCA doses were planned to be escalated from
275 to 400 mg/m(2) on day 1/q 3 weeks for six successive groups of pat
ients. The toxicity limiting dose of CBDCA in the combination was 350
mg/m(2) on day 1/q 3 weeks because of repetitive Grade IV neutropenia,
and the optimal dose of CBDCA was 325 mg/m(2) on day 1/q 3 weeks, off
ering a 86.4% NVB and a 92.6% CBDCA relative dose-intensity for the fi
rst 9 weeks. Responses were observed at each step. This study demonstr
ates 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.