title: Preemptive leucovorin administration minimizes pralatrexate toxicity without sacrificing efficacy.
abstract: Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a novel antifolate with a higher affinity for tumor cells than methotrexate, Food and Drug Administration (FDA) approved for use in relapsed and refractory peripheral T-cell lymphoma (PTCL) and transformed mycosis fungoides (T-MF). Patients with T-MF have a higher incidence of adverse events than patients with other lymphomas, necessitating a lower recommended dose of 15 mg/m(2) (vs. 30 mg/m(2) for PTCL). Dose-limiting toxicity (DLT) mucositis occurs in about 25% of patients with T-MF, but milder mucositis is observed in almost all patients with T-MF, frequently leading to therapy discontinuation despite clinical response. Leucovorin rescue is the standard of care for high-dose methotrexate therapy, but has not been studied or recommended for use with PDX. We report our clinical experience using leucovorin with PDX (30 mg/m(2)) with good clinical response and no DLTs. Prophylactic leucovorin deserves further investigation in prospective clinical trials to allow patients with cutaneous lymphomas to receive the full benefit of PDX therapy without intolerable toxicity.
authors: Department of Dermatology, University of Pittsburgh Medical Center , Pittsburgh, PA , USA.
authors: Ellen
authors: E
authors: Koch
authors: Sara K
authors: SK
authors: Story
authors: Larisa J
authors: LJ
authors: Geskin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000630:Aminopterin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D009182:Mycosis Fungoides / Q000175:diagnosis / Q000188:drug therapy; D011292:Premedication; D012867:Skin / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D005493:Folic Acid Antagonists; D000630:Aminopterin; D002955:Leucovorin