Medical Pharmacology Chapter 33-34:  Anticancer Drugs

• Antimetabolites

  • Antifolate Analogues: Pralatrexate (Folotyn)

    • Pralatrexate (Folotyn)

    • Pralatrexate (Folotyn) is another antifolate analog which inhibits DNA, RNA and protein synthesis by means of competitive inhibition for the dihydrofolate reductase:folate binding site.³

      • Pralatrexate is a 10-deaza-aminopterin antifolate analog.

        • This analog was intended to be a better substrates for the RFC-1 (reduce folate) carrier protein.

        • Pralatrexate not only inhibits dihydrofolate reductase but also inhibits enzymes associated with de novo purine nucleotide biosynthesis as well as inhibiting thymidylate synthase.³

          • Similar to methotrexate and pemetrexed, this agent is excreted in the urine and in the presence of renal disease may require dose adjustments.

      • Pralatrexate following cell entry is polyglutamylated by the enzyme folylpolyglutamate synthetase.

        • This drug is not significantly metabolized either by phase I metabolism (cytochrome P450 microsomal metabolizing system) or by phase II glucuronidases.⁷ 

        • The drug is primarily excreted unchanged (urine: about 34%-39%; feces about 34%; respiratory about 10%, exhaled).

          • The elimination half-life is about 12-18 hours.

    • Clinical Use:

      • The principal labeled indication is in the treatment of relapsed or refractory peripheral T-cell lymphoma. (Labeled Use)⁷

         

        • Trends for Treating T-Cell Lymphoma

          Attribution:  O'Connor O Discussion of new approaches in treating T-cell lymphoma including combinations of pralatrexate and romidepsin. https://www.youtube.com/watch?v=a5g5g39sB38 (7/2016) VJHemOnc-Video Journal of Hematological Oncology Youtube Channel:  https://www.youtube.com/channel/UCsQXL4_zTA-FoG9RA1tEGiw

      • With respect off label use, pralatrexate may be helpful in treating relapsed or refractory cutaneous T-cell lymphomas (CTCL)⁸

        •  

          "T-Cell Lymphoma Differential Diagnosis and CD30 Treatment"

          Attribution: Mehta-Shah N T-Cell Lymphoma Differential Diagnosis and CD30 Treatment https://www.youtube.com/watch?v=bMKRQsyv_tk OncLiveTV Youtube Channel:  https://www.youtube.com/channel/UC3aRpa3CR_w4JrxYv_r_pDg CHOP treatment:  combination of Cyclophosphamide + Doxorubicin hydrocholoride (Hydroxydaunorubicin) + Vincristine (Oncovin) + Prednisone

        •  

          Update on T-Cell Lymphoma | LFR Webinars

          Attribution:   Jain S Update on T-Cell Lymphoma | LRF Webinars https://www.youtube.com/watch?v=j-uL72hEN4k (10/2021) Lymphoma Research Foundation Youtube Channel:  https://www.youtube.com/channel/UCtne_KnvT-1sC9QgwH5xAwA

    • Adverse Effects:³

      • Principal side effects: myelosupression, skin rash, diarrhea, mucositis, fatigue.

      • Toxicities related to pralatrexate administration may be diminished with folic acid and vitamin B₁₂ vitamin supplementation.

        • "Leucovorin Rescue in Managing Recurrent Pralatrexate Induced Mucositis"

          Attribution: Haddad P Leucovorin Rescue in Managing Recurrent Pralatrexate Induced Mucositis. https://www.youtube.com/watch?v=PhLw2q9FjzE (1/2012) Oncology TV Youtube Channel:  https://www.youtube.com/channel/UC6DdH8ovsjVeZkRgON5PCpw