Failure of pretreatment with intravenous folic acid to alter the cumulative hematologic toxicity of lometrexol.
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چکیده
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منابع مشابه
Cellular but not plasma pharmacokinetics of lometrexol correlate with the occurrence of cumulative hematological toxicity.
Lometrexol inhibits the first folate-dependent enzyme in de novo purine biosynthesis and is avidly polyglutamated and retained in tissues expressing folylpolyglutamate synthetase. Although clinical studies have been limited by cumulative toxicity, preclinical studies show that pretreatment with folic acid can protect normal tissue while maintaining tumor cytotoxicity. Therefore, a Phase I study...
متن کاملAugmentation of the therapeutic activity of lometrexol -(6-R)5,10-dideazatetrahydrofolate- by oral folic acid.
Recent clinical trials with lometrexol [(6R)-5,10-dideazatetrahydrofolate] have revealed a level of toxicity in humans that was not predicted on the basis of previous in vivo preclinical studies. Because standard laboratory animal diets contain high levels of folic acid relative to human folate intake, the toxicity and therapeutic activity of lometrexol was studied in mice under conditions of r...
متن کاملClinical pharmacokinetics of the antipurine antifolate (6R)-5,10- dideaza-5,6,7,8-tetrahydrofolic acid (Lometrexol) administered with an oral folic acid supplement.
(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid (lometrexol) is an antipurine antifolate which selectively inhibits glycinamide ribonucleotide formyltransferase. Lometrexol pharmacokinetics were evaluated in 17 patients (32 courses) as part of a Phase I study in which folic acid supplementation was used to improve tolerance to the drug, its clinical utility being previously limited by severe cum...
متن کاملClinical Pharmacokinetics of the Antipurine Antifolate (6R)-5,1O- Dideaza-5,6,7,8-tetrahydrofolic Acid (Lometrexol) Administered with an Oral Folic Acid Supplement1
(6R)-5,1O-Dideaza-5,6,7,8-tetrahydrofolic acid (lometrexol) is an antipurine antifolate which selectively inhibits glycinamide ribonucleotide formyltransferase. Lometrexol pharmacokinetics were evaluated in 17 patients (32 courses) as part of a Phase I study in which folic acid supplementation was used to improve tolerance to the drug, its clinical utility being previously limited by severe cum...
متن کاملPhase I study of the antipurine antifolate lometrexol (DDATHF) with folinic acid rescue.
Lometrexol (5,10-dideazatetrahydrofolic acid) is a new antifolate that is highly selective in inhibiting the key enzyme of purine synthesis glycinamide ribonucleotide formyltransferase. The most promising preclinical features of lometrexol in animal models were its significant activity against a broad panel of solid tumors, the schedule dependency of its antitumor activity, and the availability...
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ورودعنوان ژورنال:
- Journal of the National Cancer Institute
دوره 88 20 شماره
صفحات -
تاریخ انتشار 1996