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/m² (vs. 30 mg/m² 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/m²) 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.

Keywords::

• CTCL
• pralatrexate
• leucovorin rescue

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This study was supported in part by SPORE NIH 5P50CA121973-03 Project 5 (to L.G.) and by Grant Numbers UL1 RR024153 from the National Center for Research Resources (NCRR) and NIH (to L.G). The project was also supported by the National Institutes of Health through Grant Numbers UL1 RR024153 and UL1TR000005 (to the UPMC Montefiore Clinical and Translational Research Center).