Pralatrexate is a second generation antifolate that targets dihydrofolate reductase. It was found to have a higher affinity to reduced folate carrier type 1 (RFC-1), the primary folate transporter, and has high intracellular retention via enhanced polyglutamylation. Mucositis, rather than bone marrow toxicity, is the dose limiting toxicity (DLT) in patients. In this study, we examine whether the use of leucovorin (folinic acid) can reduce pralatrexate DLT when used in mouse xenografts, and possibly enable high dose pralatrexate treatment. Nude mice bearing H2052 mesothelioma xenografts were treated with pralatrexate at normal and toxic doses with or without leucovorin administration 24 hours later. Tumors were measured three times weekly and toxicity monitored through weight loss. Leucovorin was found to abrogate pralatrexate toxicities at high doses without sacrificing efficacy. These results demonstrate that high dose pralatrexate with subsequent leucovorin rescue may be a viable treatment strategy in mesothelioma and other cancers.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A266.

Citation Format: Philip M. Tedeschi, Iqra Farooqi, Yamini Kathari, Joseph R. Bertino. Leucovorin rescue of high dose pralatrexate in mesothelioma xenografts. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A266.

Copyright © November 2013, American Association for Cancer Research
2013