Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma.
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Foss FM
Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma.
Expert Opin Drug Metab Toxicol. 2011 Sep;7(9):1141-52. doi: 10.1517/17425255.2011.595404. Epub 2011 Jul 5.
- PubMed ID
- 21726160 [ View in PubMed]
- Abstract
INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T-cell neoplasms. Most patients with PTCL have a poor outcome with conventional therapies and are not cured without stem-cell transplantation. Pralatrexate, a novel antifolate chemotherapeutic agent, was rationally designed to impede folate metabolism by inhibiting dihydrofolate reductase (DHFR) and to be more efficiently internalized into tumor cells. Pralatrexate is the first drug that is FDA approved for patients with relapsed and refractory PTCL. AREAS COVERED: Pralatrexate has been used as a single agent and in combination with other agents in clinical trials for non-Hodgkin's lymphoma and Hodgkin's disease as well as in solid tumors. This review will cover the development of pralatrexate, the pharmacokinetics of pralatrexate, preclinical findings with pralatrexate and clinical studies of pralatrexate in hematologic malignancies. EXPERT OPINION: Pralatrexate has significant activity in vitro, and in early Phase I/II trials, responses were noted in patients with aggressive T-cell lymphomas. The Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma trial demonstrated the activity of pralatrexate across a spectrum of heavily pretreated patients with different aggressive T-cell lymphoma subtypes, and studies in cutaneous T-cell lymphoma have shown efficacy at different doses and schedules. The most frequent adverse events in these trials were mucositis, reversible thrombocytopenia and fatigue.
DrugBank Data that Cites this Article
- Drugs
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Pralatrexate Serum albumin Protein Humans NoBinderDetails