A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline

Purpose: The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. Methods: This phase-I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m² and PTX 150 mg/m², administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m² until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m² until the MTD was reached. Results: Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m² while PLD escalated from 30 mg/m². At 40 mg/m ², PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m² and escalating doses of PTX starting at 160 mg/m². At PTX 170 mg/m² and dose-limiting neutropenic fever occurred in two of five patients. Out of 19 evaluable patients, 10 (52.6%) achieved objective response (one complete response and nine partial response), and 5 had stable disease. Conclusions: The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m², respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m²) and PTX (150-160 mg/m²) constitutes an active regimen with mild toxicity that merits further study.