D Pinkel1. 1. Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract
PURPOSE: This review is intended to provide a concise portrayal of the background, rationale, and current use of intravenous infusions of mercaptopurine (6MP) in patients with acute leukemia. DESIGN: After a brief description of the mode of action of 6MP and the formulation, pharmacokinetics, and history of its intravenous administration, the rationale for current use of intravenous 6MP infusion is explained. Subsequently, the review summarizes and discusses clinical experience with intravenous 6MP alone and in combination with intravenous methotrexate (Mtx) and cytarabine (Ara-C). RESULTS: Although still an investigative drug, intravenous 6MP has been used for 40 years and currently is being administered extensively to children with previously untreated acute lymphoid leukemia (ALL) in frontline protocol studies. The reasons are the better and more consistent bioavailability of intravenous versus oral MP, higher blood and CSF levels, compliance, and preliminary evidence suggesting superior remission experience for intravenous Mtx and 6MP than for Mtx alone. The apparent lack of late adverse sequelae with 6MP as compared with other antileukemia drugs adds to this interest. CONCLUSION: The new life of intravenous 6MP at age 40 years illustrates the need for continued investigation of significant anticancer drugs as insights and technology progress.
PURPOSE: This review is intended to provide a concise portrayal of the background, rationale, and current use of intravenous infusions of mercaptopurine (6MP) in patients with acute leukemia. DESIGN: After a brief description of the mode of action of 6MP and the formulation, pharmacokinetics, and history of its intravenous administration, the rationale for current use of intravenous 6MP infusion is explained. Subsequently, the review summarizes and discusses clinical experience with intravenous 6MP alone and in combination with intravenous methotrexate (Mtx) and cytarabine (Ara-C). RESULTS: Although still an investigative drug, intravenous 6MP has been used for 40 years and currently is being administered extensively to children with previously untreated acute lymphoid leukemia (ALL) in frontline protocol studies. The reasons are the better and more consistent bioavailability of intravenous versus oral MP, higher blood and CSF levels, compliance, and preliminary evidence suggesting superior remission experience for intravenous Mtx and 6MP than for Mtx alone. The apparent lack of late adverse sequelae with 6MP as compared with other antileukemia drugs adds to this interest. CONCLUSION: The new life of intravenous 6MP at age 40 years illustrates the need for continued investigation of significant anticancer drugs as insights and technology progress.