[The need for a better definition of therapeutic indications of carboxypeptidase in delayed elimination of methotrexate].
OBJECTIVE
High dose methotrexate (HD-MTX) may cause nonhaematological and haematological toxicities. MTX overexposure may be subsequent to administration errors or to delayed renal elimination resulting from MTX nephrotoxicity. The rescue agent carboxypeptidase rapidly hydrolyses MTX to inactive metabolites. However, current criteria for carboxypeptidase use are not well defined. We retrospectively evaluated the number of patients how should have received the drug if the criteria were applied, but who didn't receive it, and analysed their toxicities.


METHODS
Patients treated at our institution in 2004 and 2005 and presenting the following criteria: concentrations of MTX at H48 >or= 3 microM, or impaired renal function, were considered. Post-course tolerance was recorded and graded. Recovery of renal function was followed-up periodically up to the 3rd month following the end of treatment.


RESULTS
Twenty courses over 301 (7%) and 18 patients over 120 exhibited at least one criterion. Grade 3-4 toxicity was observed in 30% of the courses, including 2 severe acute renal impairment. Renal function decreased in most patients but had recovered upon the 3rd month in all but 2 patients.


CONCLUSIONS
Despite a higher rate of toxicity than in general population, most of the patients recovered from it. Considering the cost of this treatment, the criteria for its therapeutic use could be restricted to concentration of MTX at H48 superior at 10 microM, associated with renal impairment.
Blasco
Hélène
H
Laboratoire de Pharmacologie et Toxicologie, CHRU Bretonneau, Tours, France.
Silly
Stéphanie
S
Tournamille
Jean-François
JF
Gyan
Emmanuel
E
Sénécal
Delphine
D
André
Virginie
V
Colombat
Philippe
P
Le Guellec
Chantal
C
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002268:Carboxypeptidases / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007674:Kidney Diseases / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D002268:Carboxypeptidases; D008727:Methotrexate