Cutaneous T-Cell Lymphoma Medication

Updated: Jun 23, 2017
  • Author: Lauren C Pinter-Brown, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

Medication Summary

Cutaneous T-cell lymphomas are a heterogeneous group of entities. One should distinguish indolent, low-risk mycosis fungoides and Sézary syndrome from aggressive HTLV-1–associated adult T-cell leukemia/lymphoma. [128]

Treatment for early stage cutaneous T-cell lymphomas includes topical therapies with or without interferon alfa or oral agents, while advanced-stage patients are treated with chemotherapy and novel agents. Multiagent cytotoxic regimens may be palliative, but they seem to lack a demonstrated survival benefit. [6]

Novel therapies for cutaneous T-cell lymphoma include bexarotene, which has demonstrated efficacy in advanced refractory cases of the disease. Other novel agents include the following:

  • IL-2 fusion toxin (Ontak)
  • IL-12
  • Pentostatin (a potent adenosine deaminase inhibitor)
  • Forodesine
  • Gemcitabine [129]
  • Histone deacetylase inhibitors (eg, romidepsin, [130] depsipeptide)
  • NF-kappa-B inhibitors
  • Cytokine-receptor antagonists
  • Immunomodulatory therapies
  • Allogeneic stem cell therapy

Forodesine is a potent inhibitor of purine nucleoside phosphorylase that promotes apoptosis in T- and B- cells through intracellular accumulation of deoxyguanosine triphosphate. In a phase II study of oral forodesine therapy in 144 patients with CTCL who had already failed three or more systemic therapies, no patients achieved complete remission but 11% achieved partial remission and 50% had stabilization of disease. [131]

The value of new therapeutic approaches to cutaneous T-cell lymphoma needs to be critically assessed with regard to overall survival and disease-specific survival.

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Antineoplastics, Other

Class Summary

These agents inhibit cell growth and proliferation.

Chlorambucil (Leukeran)

Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.

Vorinostat (Zolinza)

Vorinostat is a histone deacetylase (HDAC) inhibitor. HDAC inhibition causes hypoacetylation of core nucleosomal histones, condenses chromatin structure, and represses gene transcription. This agent is indicated for treatment of progressive, persistent, or recurrent cutaneous T-cell lymphoma.

Methotrexate (Trexall, Otrexup, Rasuvo)

Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase, an enzyme needed to make DNA.

Etoposide (Toposar)

Etoposide inhibits topoisomerase II and causes DNA strand breakage, resulting in the arrest of cell proliferation in the late S or early G2 portion of the cell cycle.

Romidepsin (Istodax)

Romidepsin is a histamine deacetylase (HDAC) inhibitor. It is indicated for cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy.

Denileukin diftitox (Ontak)

This product was discontinued in January 2014. This is a fusion protein (amino acid sequence of diphtheria linked to IL-2 amino acid sequence) that selectively delivers cytotoxic activity of diphtheria toxin to targeted cells. Denileukin diftitox is used only in T-cell lymphoma in which malignant cells express the CD25 component of the IL-2 receptor. It interacts with the high-affinity IL-2 receptor on the surface of malignant cells to inhibit intracellular protein synthesis, which in turn causes cell death.

Carmustine (BiCNU)

Carmustine alkylates and cross-links DNA strands, inhibiting cell proliferation.

Mechlorethamine (Mustargen)

This is a topical nitrogen mustard that, as an alkylating agent, inhibits DNA replication.

Bexarotene (Targretin)

Bexarotene (Targretin) is an X-receptor–specific retinoid. The receptor works as transcription factors that regulate genes that control cellular differentiation and proliferation. It may inhibit sebaceous gland differentiation and abnormal keratinization.

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Immunomodulators

Class Summary

These agents may modulate the host immune system to inhibit the growth and proliferation of malignant cells.

Interferon alfa 2b (Intron-A)

Interferon alfa 2b is a protein product manufactured by recombinant DNA technology. Its mechanism of antitumor activity is not clearly understood. However, direct antiproliferative effects against malignant cells and modulation of the host immune response may play important roles.

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Antineoplastics, Monoclonal Antibody

Class Summary

Monoclonal antibodies against a T-cell antigen may inhibit cell growth and proliferation of malignant cells.

Alemtuzumab (Campath, Lemtrada)

Alemtuzumab is a monoclonal antibody against CD52, an antigen found on B cells, T cells, and almost all CLL cells. It binds to the CD52 receptor of lymphocytes, slowing the proliferation of leukocytes.

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Topical Skin Products

Class Summary

Agents that induce secretion of interferon and other cytokines have shown efficacy. The topical alkylating agent, mechlorethamine, has also been shown to be effective.

Imiquimod 5% cream (Aldara, Zyclara)

This agent binds to Toll-like receptors 7 and 8 and induces the secretion of interferon alfa and other cytokines. Its mechanism of action is unknown.

Mechlorethamine topical (Valchlor)

Mechlorethamine topical is an alkylating agent that inhibits rapidly proliferating cells. It is indicated for mycosis fungoides-type cutaneous T-cell lymphoma.

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Retinoid-like Agents

Class Summary

Retinoids regulate genes that control cellular differentiation and proliferation.

Alitretinoin

Alitretinoin is a retinoid, related to vitamin A. It has immunomodulating and anti-inflammatory effects. Binds to both retinoid acid receptor and retinoid X receptor.

Tazarotene gel (Avage, Fabior, Tazorac)

This agent is a retinoid prodrug with an active metabolite that modulates the differentiation and proliferation of epithelial tissue. It may also have anti-inflammatory and immunomodulatory properties.

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Rayos)

Prednisone is an immunosuppressant; it should be used together with other agents such as low-dose chlorambucil and interferon alfa. Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body.

Prednisolone (Orapred, Pediapred, Millipred)

It is an immunosuppressant; it should be used together with other agents such as low-dose chlorambucil and interferon alfa. Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body.

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