PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “AMINOPTERIN”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1983

Phase I trial of 10-deaza-aminopterin in patients with advanced cancer.

The clinical effects of 10-deaza-aminopterin, an inhibitor of dihydrofolate reductase with a better therapeutic index against several murine tumors than that of methotrexate, were examined during the course of a phase I study in patients with advanced malignant neoplasms. Three escalating dose schedules were explored: single iv injections once daily, single iv injections twice weekly, and continuous infusion. The maximum tolerated doses were: single injections at a dose of 7 mg/m2/day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for four to six doses; and continuous infusion at a dose of 3 mg/m2/day for 5-6 days in patients with solid tumors and until bone marrow hypoplasia in patients with leukemia. Mucositis was dose-limiting in all schedules. Occasionally, mild leukopenia, thrombocytopenia, and skin rash were noted. A minor antitumor response was seen in a patient with gallbladder carcinoma. Marked leukemic cell kill was observed in several patients with acute leukemia or blastic phase of chronic myelogenous leukemia. Disease-oriented phase II trials are planned at this Center for several tumor varieties.

Adult↗
PubMed1996

A case for the use of aminopterin in treatment of patients with leukemia based on metabolic studies of blasts in vitro.

Clinical and laboratory investigations during the past four decades have resulted in numerous schedules, doses, and routes of delivery for methotrexate (MTX). It remains as an important drug for the treatment of children with acute lymphoblastic leukemia (ALL). Aminopterin (AMT) was the initial antifolate showing promise as an anticancer drug. It is more potent than MTX and also is known to be accumulated more efficiently than MTX in model systems. Because Whitehead et al. (Blood, 76: 44-49, 1990) have shown that MTX accumulation by blasts at diagnosis is of prognostic significance in children with ALL, we reasoned that if accumulation of a "stoichiometric inhibitor" of dihydrofolate reductase by leukemic blasts was of prognostic importance, then whether it was AMT or MTX may be relevant only with respect to the absolute dose. To compare MTX and AMT metabolism, we incubated lymphoblasts with 1 microM radiolabeled drug in vitro. MTX and AMT accumulation by ALL cells (n = 24) was 0.7 +/- 0.7 and 1.47 +/- 0.9 pmol/10(6) cells, respectively. Based on the data of Whitehead et al., this predicts pharmacological success in 59 and 84% of the MTX and AMT groups, respectively. Moreover, 5 of 10 patients considered poor risks based on MTX accumulation would be "cures" based on AMT uptake. Even at only 0.1 microM AMT, a concentration at which there is little accumulation of MTX, 5 of 11 patients studied would be "pharmacological cures" based on AMT uptake. Accumulation of AMT by blasts from 11 patients with T-cell-lineage ALL and 5 patients with acute myelogenous leukemia was also found to be twice the uptake of MTX. These data allow the suggestion that AMT, despite increased potential for toxicity, may be useful in children who are identified as poor risks with respect to MTX uptake.

Aminopterin↗