Phase I trial of liposomal encapsulated doxorubicin (Myocet™M; D-99) and weekly docetaxel in advanced breast cancer patients

Background: We conducted a phase 1 trial to determine the safety and maximum tolerated dose (MTD) of non-pegylated liposome-encapsulated doxorubicin (Myocet (TM); D-99) administered with weekly docetaxel in metastatic breast cancer (MBC) patients. Patients and methods: Twenty-one patients with no prior chemotherapy for MBC received D-99 (60 or 50 mg/m(2)) intravenously (i.v.) on day 1 and escalating doses of docetaxel (25, 30 and 35 mg/m(2)) i.v. on days 1 and 8 in cohorts of three to six patients. Treatment cycles were repeated every 21 days for a maximum of six cycles. Results: The maximum tolerated dose (MTD) was 50 mg/m(2) of D-99 in combination with 25 mg/m(2) of weekly docetaxel. The most common grade 4 toxicity was neutropenia that occurred in 42 (41%) of treatment cycles, with 10 hospitalizations for febrile neutropenia. Serious protocol-defined cardiac events occurred in three (14%) patients, with two (10%; 95% confidence interval [CI] 1% to 30%) developing congestive heart failure (CHF) after a total cumulative anthracycline dose (adjuvant doxorubicin + D-99) of 540 mg/m(2). Conclusions: D-99 in combination with weekly docetaxel, at the doses and schedule as administered in this trial, is not recommended for phase II testing. Additional trials, using different doses and schedules, are required to evaluate the potential side-effects and efficacy of D-99 and docetaxel.