Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.