High-dose methotrexate in acute lymphoblastic leukemia: Where is the evidence for its continued use?

Elpis Mantadakis, Peter D. Cole, Barton A. Kamen

Research output: Contribution to journalShort survey

32 Scopus citations

Abstract

High-dose intravenous methotrexate is an important component of many effective chemotherapeutic regimens for childhood acute lymphoblastic leukemia (ALL). Its use has a strong pharmacologic rationale: to overcome mechanisms of resistance of the malignant cells and to achieve cytotoxic concentrations in sanctuary sites for lymphoblasts. Although therapeutic progress in ALL during the past 4 decades has been closely associated with more widespread use of intravenous methotrexate and in progressively larger doses, little data exist to clearly support the use of high-dose intravenous methotrexate over a regimen of prolonged administration of low-dose methotrexate. The implied superiority of intravenous methotrexate mainly stems from studies that used identical leucovorin rescue with low-dose methotrexate or from studies of upfront window therapy in untreated children with ALL in which single standard doses of oral methotrexate were compared with high-dose intravenous methotrexate with leucovorin rescue. The evidence favoring administration of intravenous methotrexate for children with ALL is critically reviewed. Despite its extensive use, high-dose intravenous methotrexate has not been proved conclusively to be more effective than less toxic, less labor intensive, and less costly methods of methotrexate administration.

Original languageEnglish (US)
Pages (from-to)748-755
Number of pages8
JournalPharmacotherapy
Volume25
Issue number5 I
DOIs
StatePublished - May 1 2005

Keywords

  • ALL
  • Acute lymphoblastic leukemia
  • Leucovorin
  • Methotrexate

ASJC Scopus subject areas

  • Pharmacology (medical)

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