A phase II study of continuous infusion of trimetrexate in patients with refractory acute leukemia.

Abstract

Trimetrexate, a second-generation folate antagonist, is a potent inhibitor of dihydrofolate reductase with a broader spectrum of activity and different mechanism of entry and intracellular accumulation than methotrexate. Six patients with refractory or relapsed acute leukemia were treated with a 5-day continuous infusion of trimetrexate of 8 mg/m2/day after an initial loading dose of 4 mg/m2 to achieve a target plasma concentration of 0.2-0.5 microM. In 4 patients with peripheral blasts at study entry, transient decrease or disappearance of blasts was observed, although no decrease of bone marrow blasts occurred. Mucositis was dose-limiting and severe in 4 patients. Neutrophil and platelet nadirs occurred on day 5-12 postinfusion. Because of dose-limiting mucositis, this dose schedule of trimetrexate is not recommended for further studies in refractory acute leukemia. However, other dose schedules (24- to 72-hr infusions) and its use as a modulating agent with thiopurines or leucovorin in patients that are resistant to methotrexate should be explored.

• Authors: A Kheradpour, E Berman, E Göker, J T Lin, W P Tong, J R Bertino
• Journal: Cancer investigation (Cancer Invest) Vol. 13 Issue 1 Pg. 36-40 ( 1995) ISSN: 0735-7907 [Print] England
• PMID: 7834472 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Trimetrexate

Topics

• Adult
• Aged
• Female
• Humans
• Infusions, Intravenous
• Leukemia, Myeloid, Acute (drug therapy)
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Trimetrexate (blood, therapeutic use)