@article {Brigitte:20 October 2004:0027-8874:1557,
	author = "Brigitte C. Widemann",
	author = "Frank M. Balis",
	author = "Aiman Shalabi",
	author = "Matthew Boron",
	author = "Michelle OBrien",
	author = "Diane E. Cole",
	author = "Nalini Jayaprakash",
	author = "Percy Ivy",
	author = "Valerie Castle",
	author = "Karin Muraszko",
	author = "Christopher L. Moertel",
	author = "Robert Trueworthy",
	author = "Robert C. Hermann",
	author = "Ali Moussa",
	author = "Stuart Hinton",
	author = "Gregory Reaman",
	author = "David Poplack",
	author = "Peter C. Adamson",
	title = "Treatment of Accidental Intrathecal Methotrexate Overdose With Intrathecal Carboxypeptidase G2",
	journal = "Journal of the National Cancer Institute",
	volume = "96",
	year = "20 October 2004",
	abstract = "The bacterial enzyme carboxypeptidase G&#060;INF&#062;2&#060;/INF&#062; (CPDG&#060;INF&#062;2&#060;/INF&#062;) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG&#060;INF&#062;2&#060;/INF&#062; (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&#150;600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG&#060;INF&#062;2&#060;/INF&#062; administration. Immediate symptoms of the methotrexate overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise (n = 2). Before CPDG&#060;INF&#062;2&#060;/INF&#062; administration, the median concentrations of methotrexate in CSF were 264 <IMG SRC="/iso-ents/isogrk1/mgr-s.gif" ALT="mgr"><I>M</I> (range = 97&#150;510 <IMG SRC="/iso-ents/isogrk1/mgr-s.gif" ALT="mgr"><I>M</I>) among patients who had CSF exchange and 8050 <IMG SRC="/iso-ents/isogrk1/mgr-s.gif" ALT="mgr"><I>M</I> (range = 2439&#150;16 500 <IMG SRC="/iso-ents/isogrk1/mgr-s.gif" ALT="mgr"><I>M</I>) among patients who did not. After intrathecal CPDG&#060;INF&#062;2&#060;/INF&#062; administration, methotrexate concentrations in CSF declined by more than 98&#037;. All patients recovered completely from the intrathecal methotrexate overdose except for two patients who had memory impairments. Antibodies to CPDG&#060;INF&#062;2&#060;/INF&#062; were not detected in plasma after treatment with intrathecal CPDG&#060;INF&#062;2&#060;/INF&#062;. Intrathecal CPDG&#060;INF&#062;2&#060;/INF&#062; is well tolerated, rapidly decreases CSF methotrexate concentrations, and appears to be efficacious for treating accidental intrathecal methotrexate overdoses.",
	pages = "1557-1559(3)",
	url = "http://www.ingentaconnect.com/content/oup/jnci/2004/00000096/00000020/art01557"
	doi = "doi:10.1093/jnci/djh270"
}