pralatrexate + gemcitabine

Pralatrexate + gemcitabine is an investigational combination therapy of two antineoplastic agents used mainly in clinical trials for relapsed or refractory lymphoproliferative malignancies, including Hodgkin’s lymphoma, peripheral T-cell lymphoma, and B-cell lymphoma[1][3][9]. - **Pralatrexate** is a folate analog and competitive inhibitor of dihydrofolate reductase (DHFR), acting via enhanced uptake through the reduced folate carrier (RFC-1) and intracellular retention via polyglutamylation[2][6]. This disrupts folate metabolism required for DNA synthesis, resulting in inhibition of tumor growth and cell proliferation[2][6]. - **Gemcitabine** is a nucleoside analog that, following intracellular phosphorylation, inhibits DNA synthesis both by incorporation into the DNA chain (“masked chain termination”) and by reducing deoxycytidine triphosphate pools essential for DNA replication through inhibition of ribonucleotide reductase[4]. Preclinical studies have shown **synergy** between pralatrexate and gemcitabine in lymphoma models, with enhanced apoptosis and efficacy over either monotherapy[1]. The combination is highly schedule-dependent, with both sequential and simultaneous dosing explored in clinical trials to optimize tolerability and antitumor effect[1][5].

Other names

pralatrexate and gemcitabine combination