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 t rial. TMTX was administered as an intravenous bolus for five consecuti ve days at doses of 9-12 mg/m2 based on marrow response. The maximum t olerated dose was 12 mg/m2 . Hepatotoxicity was the dose-limiting toxi city. Initial dosage reductions in patients with liver disease and/or low protein concentrations may be necessary since TMTX is significantl y protein bound and cleared primarily by hepatic metabolism. The recom mended phase II dose on this dosing schedule is 9 mg/m2.