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.
Bearman
S I
SI
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Shen
D D
DD
Hinds
M S
MS
Hill
H A
HA
McDonald
G B
GB
D000328:Adult; D000527:Alprostadil / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000097:blood; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006504:Hepatic Veno-Occlusive Disease / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged
D016572:Cyclosporine; D000527:Alprostadil