Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2

Brigitte C. Widemann, Frank M. Balis, Aiman Shalabi, Matthew Boron, Michelle O'Brien, Diane E. Cole, Nalini Jayaprakash, Percy Ivy, Valerie Castle, Karin Muraszko, Christopher L. Moertel, Robert Trueworthy, Robert C. Hermann, Ali Moussa, Stuart Hinton, Gregory Reaman, David Poplack, Peter C. Adamson

Research output: Contribution to journalArticlepeer-review

Abstract

The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally to seven cancer patients 3 to 9 hours after they had received an accidental overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG2 administration. Immediate symptoms of the methotrexate overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise (n = 2). Before CPDG2 administration, the median concentrations of methotrexate in CSF were 264 μM (range = 97-510 μM) among patients who had CSF exchange and 8050 μM (range = 2439-16500 μM) among patients who did not. After intrathecal CPDG2 administration, methotrexate concentrations in CSF declined by more than 98%. All patients recovered completely from the intrathecal methotrexate overdose except for two patients who had memory impairments. Antibodies to CPDG2 were not detected in plasma after treatment with intrathecal CPDG2. Intrathecal CPDG2 is well tolerated, rapidly decreases CSF methotrexate concentrations, and appears to be efficacious for treating accidental intrathecal methotrexate overdoses.

Original languageEnglish (US)
Pages (from-to)1557-1559
Number of pages3
JournalJournal of the National Cancer Institute
Volume96
Issue number20
DOIs
StatePublished - Oct 20 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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