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/m and T 30 mg/m. MTD was not reached when PLD was administered on days 1 and 15: only 1 of 6 patients treated with PLD 20 mg/m and T 30 mg/m 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/m on days 1 and 15 and T 35 mg/m on days 1, 8, and 15.