Phase I trial of fenretinide (4-HPR) intravenous emulsion in hematologic malignancies: A California Cancer Consortium study (PhI-42).

8073 Background: Fenretinide (4-HPR) is a cytotoxic retinoid with broad anticancer activity in preclinical studies. Due to limited bioavailability of a capsule formulation an intravenous intralipid-like emulsion formulation (4-HPR ILE) was developed to increase systemic exposures. Methods: 4-HPR was administered as a continuous intravenous infusion for 120 hrs every 21 days. Systemic toxicities, responses, and pharmacokinetics were assessed. Accelerated Simon design proceeded until moderate or dose-limiting toxicities (DLT) were scored on Course 1. Doses were 80 mg/m2/day to 1810 mg/m2/day. Patients with asymptomatic hypertriglyceridemia were scored separately. All patients were heavily pretreated. Results: Toxicity-evaluable patients = 25. At 1810 mg/m2/day, two patients experienced DLT hypertriglyceridemia, one with transient Grade 2 pancreatitis; at 1280 mg/m2/day (8 pts), two had asymptomatic Grade 4 hypertriglyceridemia, one experienced DLT pleural effusions; at 905 mg/m2/day (6 pts) 2 experienced as...