Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies

BACKGROUND. Pegylated liposomal doxorubicin (PEG-LD) and docetaxel have single-agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies. METHODS. Twenty-two patients were enrolled in this two-arm, accelerated, dose escalation trial. Both drugs were administered on Days 1 and 15 of a 28 day cycle. In Arm A, dose escalation proceeded from a sequence and starting dose of 15 mg/m² PEG-LD and 30 mg/m² docetaxel. In Arm B, dose escalation proceeded from a sequence and starting dose of 30 mg/m² docetaxel and 15 mg/m²pEG-LD. In both arms, the dose of each drug was increased alternately by 5 mg/m² at each dose level. RESULTS. The MTD for Arm A was 20 mg/m² PEG-LD and 40 mg/m² docetaxel, both of which were administered on Days 1 and 15 of a 28-day cycle. The MTD for Arm B was 35 mg/m² docetaxel and 20 mg/m² PEG-LD, both of which were administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicities were Grade 3 (according to the National Cancer Institute Common Toxicity Criteria) skin toxicity and thrombocytopenia. One partial response was observed and stable disease was documented for three patients. CONCLUSIONS. The recommended sequence and dose is 20 mg/m² PEG-LD followed by 40 mg/m² docetaxel on Days 1 and 15 of a 28-day cycle in Phase II trials for patients with breast and ovarian carcinoma to establish the efficacy of this well tolerated regimen.