Phase i clinical trial of pegylated liposomal doxorubicin and docetaxel in patients with advanced solid tumors

Objective: The primary objective of this study was to determine the maximum tolerated dose (MTD) of pegylated liposomal doxorubicin (PLD) and docetaxel (T) administered in 4 week cycles in patients with advanced solid tumors. Patients and Methods: Patients were treated with intravenous PLD on day 1 and T on days 1, 8, and 15. Once the MTD was reached the schedule of PLD was changed to days 1 and 15 to explore an alternative and potentially more manageable dosing schedule. Results: Thirty-two patients were enrolled. A total of 106 cycles (median, 2 cycles; range, <1-13 cycles) of chemotherapy were administered. Three patients experienced dose-limiting toxicities which were stomatitis, anorexia, esophagitis, neutropenic fever, fatigue, and muscular weakness. When PLD was given on day 1, the MTD was PLD 33 mg/m² and T 30 mg/m ². MTD was not reached when PLD was administered on days 1 and 15: only 1 of 6 patients treated with PLD 20 mg/m² and T 30 mg/m ² developed dose-limiting toxicities. The most common grade 3 or 4 hematologic toxicity was grade 3 neutropenia in 5 patients and grade 4 in 5. Two patients developed neutropenic fever. The most common grade 3 or 4 nonhematologic toxicity was grade 3 fatigue in 9 patients and grade 4 in 1. There was 1 confirmed PR, 2 unconfirmed PRs, and 12 patients with Sd. Conclusions: This combination of PLD and T was found to be feasible and tolerable. The recommended dose for phase II studies is PLD 20 mg/m² on days 1 and 15 and T 35 mg/m² on days 1, 8, and 15.