Carboxypeptidase-G2 rescue in cancer patients with delayed methotrexate elimination after high-dose methotrexate therapy.
High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G2 (CPDG2) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.
Krause
Anke S
AS
Department for Internal Medicine I, University of Cologne, Cologne, Germany. anke-drkrause@lycos.de
Weihrauch
Martin R
MR
Bode
Udo
U
Fleischhack
Gudrun
G
Elter
Thomas
T
Heuer
Theodor
T
Engert
Andreas
A
Diehl
Volker
V
Josting
Andreas
A
D000328:Adult; D000931:Antidotes / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D012516:Osteosarcoma / Q000150:complications / Q000188:drug therapy; D016896:Treatment Outcome; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage*
D000931:Antidotes; D011623:gamma-Glutamyl Hydrolase; D008727:Methotrexate