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JNCI Journal of the National Cancer Institute 2004 96(20):1557-1559; doi:10.1093/jnci/djh270
© 2004 by Oxford University Press
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© 2004 Oxford University Press

BRIEF COMMUNICATION

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

Affiliations of authors: Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD (BCW, FMB, MOB, DEC, NJ); Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD (AS, MB, PI); University of Michigan, Ann Arbor (VC, KM); Children's Hospital and Clinics St. Paul, St. Paul, MN (CLM); University of Kansas Medical Center, Kansas City (RT); Northwest Georgia Oncology Centers, PC, Marietta, GA (RCH); Hillcrest Medical Center, Tulsa, OK (AM); Kansas City Cancer Center, Kansas City, MO (SH); Children's Oncology Group, Arcadia, CA (GR); Texas Children's Cancer Center, Houston (DP); Children's Hospital of Philadelphia, Philadelphia, PA (PCA)

Correspondence to: Brigitte C. Widemann, MD, Pediatric Oncology Branch, National Cancer Institute, 10 Center Dr., Bldg. 10, Rm. 13C103, Bethesda, MD 20892-1920 (e-mail: bw42y{at}nih.gov)

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 = 2439–16 500 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.


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Correspondence about this Article

Re: Treatment of Accidental Intrathecal Methotrexate Overdose
Sophie Gosselin and Geoffrey K. Isbister
J Natl Cancer Inst 2005 97: 609-610. [Extract] [Full Text] [PDF]

RESPONSE: Re: Treatment of Accidental Intrathecal Methotrexate Overdose
Brigitte C. Widemann, Frank M. Balis, and Peter C. Adamson
J Natl Cancer Inst 2005 97: 610-611. [Extract] [Full Text] [PDF]



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S. Gosselin and G. K. Isbister
Re: Treatment of Accidental Intrathecal Methotrexate Overdose
J Natl Cancer Inst, April 20, 2005; 97(8): 609 - 610.
[Full Text] [PDF]


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