Glucarpidase following high-dose methotrexate: update on development.
Glucarpidase (Carboxypeptidase G2 or Voraxaze) is a recombinant enzyme that belongs to the class of carboxypeptidases which are naturally occurring enzymes. Glucarpidase is able to cleave methotrexate (MTX) into non-cytotoxic metabolites that may help prevent or minimise subsequent toxicities such as renal failure. In this review, the authors outline the discovery of the carboxypeptidase class of enzymes and the pre-clinical data demonstrating that glucarpidase is highly effective in the rapid reduction of MTX levels. The authors summarise the compassionate use studies of glucarpidase for patients with nephrotoxicity following high dose MTX or with very high post-MTX levels and the current developmental status of the drug. In conclusion, glucarpidase has been shown to be very useful in emergency situations following administration of high-dose MTX. Glucarpidase has yet to receive marketing approval in the EU or USA, and we await further data from In conclusion, glucarpidase Phase I/II studies assessing routine prophylactic administration following high-dose methotrexate.
Patterson
Daniel M
DM
UCL Cancer Institute and University College Hospital, Department of Oncology, London, UK.
Lee
Siow Ming
SM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D057176:Compassionate Use Trials; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D011623:gamma-Glutamyl Hydrolase / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D011623:gamma-Glutamyl Hydrolase; D008727:Methotrexate