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Pralatrexate is a folate analog metabolic inhibitor and antineoplastic agent designed to selectively inhibit dihydrofolate reductase (DHFR) in cancer cells that overexpress the reduced folate carrier protein-1 (RFC-1). It disrupts DNA synthesis and cell division by interfering with folate metabolism, leading to tumor growth inhibition. Pralatrexate is FDA-approved for relapsed or refractory peripheral T-cell lymphoma (PTCL) and has demonstrated higher affinity for tumor cells compared to methotrexate[5][7]. Leucovorin (folinic acid) is a chemically reduced derivative of folic acid used as a rescue agent to mitigate the toxic effects of antifolate chemotherapy such as methotrexate or pralatrexate. It protects healthy cells from antifolate toxicity without reducing anticancer efficacy[1][4]. The combination of pralatrexate with leucovorin has been explored clinically to reduce dose-limiting toxicities like mucositis in patients with cutaneous T-cell lymphoma (CTCL) and PTCL while maintaining therapeutic benefit[2][6].
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