Abstract
Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase II study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received prior chemotherapy, were initially treated with 25 mg piritrexim orally administered trice daily for four days, repeated weekly, with provision for dose escalation or reduction according to observed toxicity. Of twenty-one patients evaluable for tumour response, one patient achieved a partial response which lasted for 24 weeks. Three patients had stable disease during 12 weeks of treatment, seventeen had progressive disease. Pirtrexim was generally well tolerated, in eighteen patients the dose could be escalated. Myelotoxicity was the most frequent observed toxicity of this piritrexim regimen. Leucopenia and thrombocytopenia grade 3/4 occurred in 38% of the patients sometime during treatment. Pharmacokinetic analysis of piritrexim in three patients during the first treatment cycle, revealed peak levels 1 to 2 h after an oral dose, with a trend towards a higher peak plasma levels and AUCs on the fourth dosing day compared with the first dosing day. In conclusion, orally administered piritrexim appears to be a regimen with little activity in patients with locally advanced or metastatic breast carcinoma.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Vries, E., Gietema, J., Workman, P. et al. A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer. Br J Cancer 68, 641–644 (1993). https://doi.org/10.1038/bjc.1993.400
Issue Date:
DOI: https://doi.org/10.1038/bjc.1993.400
This article is cited by
-
Medicines associated with folate–homocysteine–methionine pathway disruption
Archives of Toxicology (2019)
-
Design and synthesis of some new piritrexim analogs as potential anticancer agents
Research on Chemical Intermediates (2018)
-
From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates
Investigational New Drugs (2006)