pralatrexate

Pralatrexate is a chemotherapy agent classified as a folate analogue metabolic inhibitor (antimetabolite). It is designed to enter cancer cells more efficiently than normal cells and to become trapped inside them after polyglutamation, increasing its intracellular retention and duration of action. The drug is marketed under the brand name Folotyn and is used in the treatment of peripheral T-cell lymphoma.

Mechanism of action

Pralatrexate is taken up by cancer cells primarily through the reduced folate carrier and is rapidly polyglutamated by folylpolyglutamate synthase, which enhances its retention and activity. Inside the cell, it inhibits dihydrofolate reductase, disrupting folate-dependent biosynthesis of thymidine and purines, and thereby impairs DNA synthesis and cell replication. The combination of selective uptake and polyglutamation contributes to a higher cytotoxic effect in malignant cells compared with some normal tissues.

Clinical use

Pralatrexate was approved by the U.S. Food and Drug Administration in 2009 for relapsed or refractory peripheral T-cell lymphoma in adults. It is administered intravenously, typically at 30 mg/m2 once weekly for six weeks within a 21-day cycle, and continued until disease progression or intolerable toxicity. To reduce mucositis and other toxicities, patients receive folic acid supplementation (commonly 400–1000 micrograms daily) beginning before the first dose and continuing throughout treatment, and vitamin B12 injections prior to starting therapy and at regular intervals during treatment. Supportive care, including antiemetics and monitoring of blood counts and liver function, is recommended.

Adverse effects commonly include mucositis, myelosuppression (neutropenia and thrombocytopenia), nausea, fatigue, liver enzyme elevations, and rash. Dose adjustments are needed for toxicity, and careful monitoring is advised during treatment.