Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies

BACKGROUND. Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies. METHODS. Twenty-six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG-LD 20 mg/m² and gemcitabine 1000 mg/m² administered on Days 1 and 15 of a 28-day cycle. RESULTS. The MTD was PEG-LD 20 mg/m² and gemcitabine 2000 mg/m² administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG-LD 25 mg/m² and gemcitabine 2000 mg/m². Other side effects included palmar-plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed. CONCLUSIONS. The recommended Phase II dose is PEG-LD 20 mg/m² with gemcitabine 2000 mg/m² on Days 1 and 15 of a 28-day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma.