Renal dysfunction during and after high-dose methotrexate.
OBJECTIVE
To evaluate renal dysfunction in adult patients encountered during and immediately after repeated administrations of high-dose methotrexate (HDMTX) for treatment of primary central nervous system lymphoma (PCNSL).


METHODS
In this single-center, retrospective, open label trial, 23 consecutive adult patients aged between 19 and 94 years diagnosed with PCNSL were given >or=4 consecutive cycles of HDMTX (8 gm/m(2)/dose) every 14 days as per institution protocol. Serum creatinine and serum methotrexate levels were measured at 24, 48 and 72 h after beginning of HDMTX infusion.


RESULTS
Forty-eight percent of all patients (30% of all HDMTX cycles) experienced a >or=200% increase in baseline creatinine during treatment. Nine percent of patients met requirements for administration of carboxypeptidase-G(2) (glucarpidase) under compassionate use from National Cancer Institute. Thirty percent of patients at the conclusion of HDMTX therapy demonstrated a NCI Common Toxicity Criteria (CTC) grade 2 or higher increase in post-treatment serum creatinine compared to pre-treatment serum creatinine amongst whom ten patients (43%) had levels outside of the normal range.


CONCLUSIONS
Renal dysfunction of CTC grade 2, 3 or 4 is common during treatment with HDMTX in the treatment of PCNSL, occurring in 40% of all cycles. Renal dysfunction persists at least 4 months following the conclusion of therapy in nearly 30% of patients. Male patients age greater than 50 years are at greatest risk of renal dysfunction.
Green
Myke R
MR
Department of Pharmacy, Intermountain Healthcare Corporation, Salt Lake City, UT, USA.
Chamberlain
Marc C
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000097:blood / Q000188:drug therapy; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D011623:gamma-Glutamyl Hydrolase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D003404:Creatinine; D011623:gamma-Glutamyl Hydrolase; D008727:Methotrexate