Phase I Clinical Trial of Pegylated Liposomal Doxorubicin and Docetaxel in Patients With Advanced Solid Tumors

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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/m2. 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/m2 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.

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