A phase I/II study of prostaglandin E1 for the prevention of hepatic venocclusive disease after bone marrow transplantation.

We conducted a phase I/II trial of prostaglandin E1 (PGE1) for the prevention of hepatic venocclusive disease (VOD). Twenty-four patients at high risk for VOD received PGE1 at four dose levels ranging from 1.25 to 10 ng/kg/min. Severe toxicity was experienced at all dose levels and was manifested as cutaneous erythema and desquamation, severe pain in dependent extremities, fluid retention and grade 4 oedema, or hypotension. In 12/24 patients, PGE1 administration was stopped prior to day 15 due to severe toxicity attributed to the drug. Three of 12 patients who received PGE1 for the entire course of treatment and 9/12 patients whose PGE1 was stopped prior to day 15 developed severe toxicity which was attributed to PGE1 (P = 0.039). Severe toxicity attributed to PGE1 was not related to either PGE1 concentration or PGE1 clearance. Six of 12 patients whose PGE1 infusion was stopped prior to day 15 and 2/12 patients who received PGE1 for the full course of treatment developed severe VOD (P = 0.19). We conclude that PGE1 causes significant toxicity in patients undergoing marrow transplantation. The ability of PGE1 to prevent severe VOD in patients at high risk remains unproven.