A phase I trial of trimetrexate (NSC352122) on a daily x 5 schedule in patients with refractory adult leukemia.
Seven adult patients with refractory acute leukemia were administered trimetrexate (TMTX), a non-classical folate antagonist, in a phase I trial. TMTX was administered as an intravenous bolus for five consecutive days at doses of 9-12 mg/m2 based on marrow response. The maximum tolerated dose was 12 mg/m2. Hepatotoxicity was the dose-limiting toxicity. Initial dosage reductions in patients with liver disease and/or low protein concentrations may be necessary since TMTX is significantly protein bound and cleared primarily by hepatic metabolism. The recommended phase II dose on this dosing schedule is 9 mg/m2.
Rodriguez
G
G
University of Texas Health Science Center, San Antonio.
Brown
T D
TD
Balis
F M
FM
Craig
J B
JB
Denham
C A
CA
Kuhn
J G
JG
Havlin
K
K
Von Hoff
D D
DD
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance; D005260:Female; D006207:Half-Life; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016597:Trimetrexate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D016597:Trimetrexate