Purpose: We performed a phase I trial of carboplatin and paclitaxel in combination with gemcitabine in order to determine the tolerability of this triplet.
Methods: Enrolled in the study were 26 patients with advanced cancer, most with non-small cell lung cancer. The patients received escalating doses of carboplatin and paclitaxel on day 1 and gemcitabine (30-min infusion) on days 1, 8, and 15 of a 28-day treatment cycle. The doses of each drug ranged from an area under the concentration-time curve (AUC) of 5 to 6 for carboplatin, 135 to 175 mg/m(2) for paclitaxel, and 300 to 1000 mg/m(2) for gemcitabine.
Results: Hematologic toxicity was the most commonly observed toxicity and was dose-limiting. During the first cycle at the recommended phase II dose, there were two instances of grade 4 neutropenia and one instance of grade 4 thrombocytopenia among six patients, none of which was dose-limiting. Cumulative hematologic toxicity emerged in subsequent cycles. Non-hematologic toxicities were mild. Five patients, all with previously untreated non-small-cell lung cancer (NSCLC), had a partial response. Nine patients with NSCLC or upper gastrointestinal malignancies experienced stable disease.
Conclusions: Based on significant neutropenia and thrombocytopenia, the regimen recommended for further study consists of carboplatin AUC 5, paclitaxel 175 mg/m(2), and gemcitabine 1000 mg/m(2) on a 28-day cycle. The antitumor activity noted suggests that further investigation of this well-tolerated combination in specific tumor types, especially NSCLC, is warranted.