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A Pilot Study of Piritrexim in Mycosis Fungoides

A Pilot Study of Piritrexim in Mycosis Fungoides Abstract To the Editor.— Piritrexim (2,4-diamino-6[2,5-dimeth-oxybenzyl]-5-methylpyrido-[2,3-D] pyrimidine) (PTX) (BW-301U) is a novel lipid-soluble antifolate that has looked promising in clinical trials.1 It is as active as methotrexate as an inhibitor of dihydrofolate reductase. However, in contrast to methotrexate, it crosses membranes by passive diffusion and may be able to overcome cellular resistance to methotrexate due to folate transport mutations. Piritrexim, unlike methotrexate, is not polyglutamated and is potentially less hepatotoxic, since it is not stored in the liver as are methotrexate polyglutamates.2 Since methotrexate is effective in the treatment of cutaneous T-cell lymphoma,3 a trial of piritrexim in mycosis fungoides seemed reasonable. Unlike methotrexate, piritrexim has little anticancer effect when given as a single dose or over 24 hours. Therefore, the low-dose long-term administration schedule effective against neoplasms was used in this study.Nine patients (six women and three men; age range, 41 to 71 years) entered References 1. Feun LG, Gonzalez R, Savaraj N, et al. Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration . J Clin Oncol. 1991;9:464-467. 2. Clendeninn N, Collier M, Feun L, Robinson W. Prolonged low-dose administration of piritrexim (PTX): a better way to deliver an antifolate? Invest New Drugs. 1989;7:464. 3. Zackheim HS, Epstein EH Jr. Low-dose methotrexate for the Sézary syndrome . J Am Acad Dermatol. 1989;21:757-762.Crossref 4. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment . Cancer. 1981;47:207-214.Crossref 5. Bunn PA Jr, Lamberg SI. Report of the committee on staging and classification of cutaneous T-cell lymphomas . Cancer Treat Rep. 1979;63:725-728. 6. Halberg FE, Fu KK, Weaver KA, Zackheim HS, Epstein EH Jr, Wintroub BU. Combined total body x-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides . Int J Rad Oncol Biol Phys. 1989;17:427-432.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

A Pilot Study of Piritrexim in Mycosis Fungoides

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References (6)

Publisher
American Medical Association
Copyright
Copyright © 1992 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1992.01680140145023
Publisher site
See Article on Publisher Site

Abstract

Abstract To the Editor.— Piritrexim (2,4-diamino-6[2,5-dimeth-oxybenzyl]-5-methylpyrido-[2,3-D] pyrimidine) (PTX) (BW-301U) is a novel lipid-soluble antifolate that has looked promising in clinical trials.1 It is as active as methotrexate as an inhibitor of dihydrofolate reductase. However, in contrast to methotrexate, it crosses membranes by passive diffusion and may be able to overcome cellular resistance to methotrexate due to folate transport mutations. Piritrexim, unlike methotrexate, is not polyglutamated and is potentially less hepatotoxic, since it is not stored in the liver as are methotrexate polyglutamates.2 Since methotrexate is effective in the treatment of cutaneous T-cell lymphoma,3 a trial of piritrexim in mycosis fungoides seemed reasonable. Unlike methotrexate, piritrexim has little anticancer effect when given as a single dose or over 24 hours. Therefore, the low-dose long-term administration schedule effective against neoplasms was used in this study.Nine patients (six women and three men; age range, 41 to 71 years) entered References 1. Feun LG, Gonzalez R, Savaraj N, et al. Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration . J Clin Oncol. 1991;9:464-467. 2. Clendeninn N, Collier M, Feun L, Robinson W. Prolonged low-dose administration of piritrexim (PTX): a better way to deliver an antifolate? Invest New Drugs. 1989;7:464. 3. Zackheim HS, Epstein EH Jr. Low-dose methotrexate for the Sézary syndrome . J Am Acad Dermatol. 1989;21:757-762.Crossref 4. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment . Cancer. 1981;47:207-214.Crossref 5. Bunn PA Jr, Lamberg SI. Report of the committee on staging and classification of cutaneous T-cell lymphomas . Cancer Treat Rep. 1979;63:725-728. 6. Halberg FE, Fu KK, Weaver KA, Zackheim HS, Epstein EH Jr, Wintroub BU. Combined total body x-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides . Int J Rad Oncol Biol Phys. 1989;17:427-432.Crossref

Journal

Archives of Dermatology – American Medical Association

Published: Apr 1, 1992

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