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Pemetrexed disodium, a novel antifolate with multiple targets

Lookup NU author(s): Professor Nicola Curtin, Dr Andrew Hughes

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Abstract

Pemetrexed disodium is a potent new antifolate which inhibits many folate-dependent reactions that are essential for cell proliferation. Its primary target is thymidylate synthase but it also inhibits folate-dependent enzymes involved in purine synthesis. Cells that are resistant to antifolates are generally less resistant to pemetrexed, irrespective of the mechanism of resistance. Pemetrexed has shown good activity in preclinical models with human tumour cells and xenografts. In the majority of clinical trials of pemetrexed, the dose-limiting toxic effect is neutropenia; other side-effects are mostly gastrointestinal. Preclinical studies indicate that the toxic effects of pemetrexed can be reduced by dietary folate, resulting in an improved therapeutic index. Low folate status is also associated with higher levels of toxicity in patients. As a single agent pemetrexed has shown good activity against non-small-cell lung cancer, squamous-cell carcinoma of head and neck, colon cancer, and breast cancer, and it appears to be particularly active in combination with cisplatin against non-small-cell lung cancer and mesothelioma. Phase II and III studies are underway. © 2001 Elsevier Science Ltd.


Publication metadata

Author(s): Curtin, N.J., Hughes, A.N.

Publication type: Review

Publication status: Published

Journal: Lancet Oncology

Year: 2001

Volume: 2

Issue: 5

Pages: 298-306

Print publication date: 01/05/2001

ISSN (print): 1470-2045

ISSN (electronic): 1474-5488

URL: http://dx.doi.org/10.1016/S1470-2045(00)00325-9

DOI: 10.1016/S1470-2045(00)00325-9

PubMed id: 11905785


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