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Australian Prescriber Apr 2019
Review
PubMed: 31048945
DOI: 10.18773/austprescr.2019.020 -
Anti-cancer Agents in Medicinal... 2023Due to their primary effects on DNA synthesis, antimetabolites are most effective against actively dividing cells and are significantly specific to the cell cycle phase.... (Review)
Review
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A comprehensive internet-based research was planned, covering all published and unpublished studies on the subject.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.
Topics: United States; Humans; Folic Acid Antagonists; Lymphoma, T-Cell, Peripheral; Methotrexate; Neoplasm Recurrence, Local; COVID-19; SARS-CoV-2; Systematic Reviews as Topic; Meta-Analysis as Topic; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms
PubMed: 35692151
DOI: 10.2174/1871520622666220610151603 -
Dermatologic Clinics Oct 2015This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides,... (Review)
Review
This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.
Topics: Aminopterin; Antimetabolites, Antineoplastic; Apoptosis; DNA Methylation; Epigenesis, Genetic; Folic Acid Antagonists; Humans; Lymphoma, T-Cell, Cutaneous; Methotrexate; S Phase; Skin Neoplasms
PubMed: 26433846
DOI: 10.1016/j.det.2015.05.009 -
Journal of Clinical Oncology : Official... Mar 2011Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and...
PURPOSE
Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity.
PATIENTS AND METHODS
Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m(2)/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS).
RESULTS
Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
CONCLUSION
To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.
Topics: Adult; Aged; Aged, 80 and over; Aminopterin; Drug Resistance, Neoplasm; Female; Folic Acid Antagonists; Humans; International Agencies; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Remission Induction; Salvage Therapy; Standard of Care; Survival Rate; Treatment Outcome; Young Adult
PubMed: 21245435
DOI: 10.1200/JCO.2010.29.9024 -
Expert Review of Hematology Jun 2020Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and... (Review)
Review
INTRODUCTION
Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and associated with inferior outcomes. Pralatrexate is a novel folate analog, the first FDA approved drug) for the treatment of relapsed/refractory (R/R) PTCL.
AREAS COVERED
This paper provides a comprehensive review of PubMed literature describing the use of pralatrexate in R/R peripheral T-cell lymphoma. Pharmacokinetics and mechanism of action of pralatrexate are discussed as well as its clinical efficacy and safety in comparison to other agents available in R/R PTCL.
EXPERT OPINION
Pralatrexate is an active agent in relapsed/refractory PTCL with lower response rates seen in patients with angioimmunoblastic T cell lymphomas. Mucositis is the most frequently observed adverse event and this can be mitigated by the use of leucovorin along with cyanocobalamin and folic acid.
Topics: Aminopterin; Humans; Lymphoma, T-Cell, Peripheral
PubMed: 32293930
DOI: 10.1080/17474086.2020.1756257 -
Future Oncology (London, England) Jan 2013Pralatrexate is a folate analogue metabolic inhibitor manufactured by Allos Therapeutics, Inc., a wholly-owned subsidiary of Spectrum Pharmaceuticals, Inc. In both... (Review)
Review
Pralatrexate is a folate analogue metabolic inhibitor manufactured by Allos Therapeutics, Inc., a wholly-owned subsidiary of Spectrum Pharmaceuticals, Inc. In both preclinical and clinical studies, pralatrexate demonstrated activity in lymphoma. Pralatrexate was US FDA approved for the treatment of relapsed/refractory peripheral T-cell lymphoma in 2009. Approval was based on data from the PROPEL trial that demonstrated an overall response rate of 29% in a heavily pretreated patient population. The dose and schedule of pralatrexate is 30-mg/m(2) weekly for 6 weeks, given in 7-week cycles. Folate and vitamin B12 supplementation are required to minimize toxicity. The most common toxicities are mucositis, thrombocytopenia, nausea and fatigue.
Topics: Aminopterin; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Humans; Lymphoma, T-Cell; Recurrence
PubMed: 23252560
DOI: 10.2217/fon.12.168 -
Leukemia & Lymphoma Nov 2017It has been nearly 8 years since pralatrexate became the first drug approved by the U.S. Food and Drug Administration for the treatment of relapsed or refractory... (Review)
Review
It has been nearly 8 years since pralatrexate became the first drug approved by the U.S. Food and Drug Administration for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Like most drugs approved for a particular clinical indication, as much or more is learned once it enters mainstream use as in the years leading up to regulatory approval. Over the past several years, many diverse lines of research have shed new insight into both the agent, and the diseases it treats. In this review, we will bring the reader up to date on the many new aspects related to pralatrexate's pharmacology, activity across the panoply of T-cell lymphoproliferative malignancies, as well as some new and emerging guidelines that are likely to improve its safety profile. Finally, the review will close with the many new lines of evidence building a rationale for the combination of these novels: novel combination, and the vision for new platforms in PTCL care.
Topics: Aminopterin; Clinical Trials as Topic; Drug Resistance, Neoplasm; Drug Therapy; Folic Acid Antagonists; Humans; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 28738754
DOI: 10.1080/10428194.2017.1306642 -
Journal of B.U.ON. : Official Journal... 2021Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine...
PURPOSE
Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate.
METHODS
The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study.
RESULTS
The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients.
CONCLUSION
Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.
Topics: Aminopterin; Female; Humans; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Turkey
PubMed: 34565016
DOI: No ID Found -
Expert Opinion on Pharmacotherapy Mar 2013Pralatrexate is a novel antifolate agent that belongs to the class of 10-deazaaminopterins. Its clinical efficacy as a single agent in relapsed or refractory peripheral... (Review)
Review
INTRODUCTION
Pralatrexate is a novel antifolate agent that belongs to the class of 10-deazaaminopterins. Its clinical efficacy as a single agent in relapsed or refractory peripheral T-cell lymphoma (PTCL) has been established in randomized trials. Treatment with this agent is generally safe.
AREAS COVERED
This paper discusses the pharmacokinetics and efficacy of pralatrexate in T-cell lymphoma in clinical trials. In addition, the authors highlight pralatrexate-associated adverse effects and safety concerns.
EXPERT OPINION
Although established as a second-line therapy, pralatrexate offers a clinical benefit to less than one-third of patients with PTCL. In addition, toxicity of this agent can be significant, especially mucositis, immunosuppression and thrombocytopenia. Currently, the potential synergy between pralatrexate and other agents in T-cell lymphoma is being explored in a number of studies. These results will hopefully prove the validity of this approach, leading to improved quantity of life in these patients, with an acceptable comfort index.
Topics: Aminopterin; Animals; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Disease-Free Survival; Drug Screening Assays, Antitumor; Folic Acid Antagonists; Humans; Lymphoma, T-Cell
PubMed: 23409799
DOI: 10.1517/14656566.2013.770474