Title:Pralatrexate for Peripheral T-Cell Lymphoma (PTCL): Chance Only Supports The
Prepared Mind
Volume: 23
Issue: 3
Author(s): Serdar Altınay*, Alev Kural, Aykut Özmen, Deniz Tural and Yusuf Tutar
Affiliation:
- Medical Faculty, University of Health Sciences, Istanbul, Turkey
- Department of Pathology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
- Department of Molecular Oncology, Institute of Health Sciences, University of Health Sciences, Istanbul, Turkey
Keywords:
Pralatrexate, lymphoma, oncology, clinical trials, folate, metabolite.
Abstract:
Background: Due to their primary effects on DNA synthesis, antimetabolites are most effective against
actively dividing cells and are significantly specific to the cell cycle phase. Pralatrexate (PDX), an antifolate metabolite
designed to accumulate in cancer cells, was the first new agent approved by the US Food and Drug Administration for
the treatment of resistant/recurrent peripheral T-cell lymphomas. PDX was a drug that is frequently used not only for
PTCL, but also for cutaneous T-cell lymphoma (CTCL), extranodal natural killer (NK) / T-cell lymphoma.
Objective: This article reviews Pralatrexate's history, pharmacokinetics, clinical phase studies including phases I, II and
III, types of cancers it is effective on, drug side effects, inhibition mechanism and even its use in the treatment of other
cancers with innovative methods, including its antiviral effect against SARS-CoV-2 infection.
Methods: A comprehensive internet-based research was planned, covering all published and unpublished studies on the
subject. We conducted this review in accordance with Preferred Reporting Items for systematic reviews and metaanalysis
(PRISMA-P), and Cochrane Collaboration reporting items for systematic reviews and meta-analysis. The
results of the studies in the articles were recorded to include all phase studies.
Results: Pralatrexate was structurally designed to have enhanced cellular transport via RFC (reduced folate carrier
type) and be subject to more polyglutamation compared to methotrexate. The enhanced polyglutamylation ability of
pralatrexate is associated with increased tumor cell death and ultimately improved anticancer activity. Pralatrexate is
considered a promising drug for patients with recurrent and treatment-resistant PTCL with a good survival advantage.
At the same time, it is an antifolate agent with a significant advantage over methotrexate as it does not cause myelosuppression.
Conclusion: While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical
to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal
pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.
