Rescue with recombinant Carboxypeptidase G2 (CPG2) in high-dose methotrexate (HD-MTX) induced renal failure: Results in 42 patients from a German emergency protocol.

Abstract

8067 Background: Accumulation of MTX in patients (pts.) with renal failure after HD-MTX is a rare, but life-threatening complication. Recombinant CPG2 cleaves MTX into the less toxic metabolite 2,4-diamino-N-pteroic acid (DAMPA) and glutamate. We have conducted an emergency use protocol using CPG2 in pts. with delayed MTX-elimination/renal failure after HD-MTX. METHODS Pts. with MTX serum levels of >5μmol/l at 42h, >1μmol/l at 42h* or >0.4μmol/l at 48h* (* + renal insufficiency: creatinine >1.5 upper limit of normal) after start of HD-MTX (>1g/m2 MTX) were eligible. Pts. with renal insufficiency were also eligible at <42h. Concentrations of MTX and metabolites were measured by high-performance-liquid-chromatography (HPLC) in acidified serum samples. RESULTS 42 pts. (age: 10-78 years) with lymphoma (29), acute lymphoblastic leukemia (12) or germ cell tumor (1) were enroled. MTX serum levels at registration ranged from 1.01 - 1187.42μmol/l (median: 9.8). CPG2 was given at dosages ranging from 10-58units/kg i.v. at median 55h (range: 27-176h) after start of HD-MTX. Except for skin reaction grade III and fever grade II in one pt. each, CPG2 was well tolerated. Serial serum samples were available for HPLC analysis in 24 pts.. MTX serum levels rapidly declined from a median of 5.11μmol/l (range: 0.35-165.86) to 1μmol/l or less within 7-50 minutes after CPG2 administration. Serum creatinine levels remained normal in 2 pts. and returned to normal values in 21 pts. after a median of 17 days (range: 4-127). The remaining 19 pts. had median peak serum creatinine levels of 283μmol/l which subsequently declined to a median of 150μmol/l by days 1-58 after CPG2. CONCLUSIONS CPG2 is a safe and effective antidote in HD-MTX treated pts. with delayed MTX-clearance/renal failure. Further studies are needed to evaluate the efficacy of CPG2 with respect to clinical endpoints, as well as the role of this novel drug as a standard rescue agent. [Table: see text].

Cite this paper

@article{Schwartz2004RescueWR, title={Rescue with recombinant Carboxypeptidase G2 (CPG2) in high-dose methotrexate (HD-MTX) induced renal failure: Results in 42 patients from a German emergency protocol.}, author={Stefan Schwartz and Klaus Borner and Kim Mueller and Lars Fischer and Agnieszka Korfel and Theresa Atkinson and Rosalie Melton and Eckhard Thiel}, journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, year={2004}, volume={22 14_suppl}, pages={8067} }