Phase I and Pharmacokinetic Study of Oral Paclitaxel

PURPOSE: To investigate dose escalation of oral paclitaxel in combination with dose increment and scheduling of cyclosporine (CsA) to improve the systemic exposure to paclitaxel and to explore the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: A total of 53 patients received, on one occasion, oral paclitaxel in combination with CsA, coadministered to enhance the absorption of paclitaxel, and, on another occasion, intravenous paclitaxel at a dose of 175 mg/m2 as a 3-hour infusion. RESULTS: The main toxicities observed after oral intake of paclitaxel were acute nausea and vomiting, which reached DLT at the dose level of 360 mg/m2. Dose escalation of oral paclitaxel from 60 to 300 mg/m2 resulted in significant but less than proportional increases in the plasma area under the concentration-time curve (AUC) of paclitaxel. The mean AUC values ± SD after 60, 180, and 300 mg/m2 of oral paclitaxel were 1.65 ± 0.93, 3.33 ± 2.39, and 3.46 ± 1.37 μmol/L·h, respectively. Dose incr...