eMedicine Specialties > Hematology > Stem Cells and Disorders
Mycosis Fungoides: Treatment & Medication
Updated: Oct 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Conduct the evaluation and treatment of individuals with mycosis fungoides on an outpatient basis (usually). Use symptomatic treatments, emollients, or antipruritics in combination with specific topical and systemic treatment.
Mycosis fungoides treatment selection should be based on the stage and previous treatment history.3,4,13,14,15,16,17,18,19,20,21 In general, topical therapies are indicated for stage I patients, and systemic therapies or combinations of topical and systemic therapies are indicated for patients with stage IIB or greater or for patients with stage I mycosis fungoides whose condition has failed or is intolerant to topical treatments.
Sequential therapies that are stage appropriate are selected based on convenience and availability to the patient and also on short- and long-term toxicity profiles. Therapies may also be selected based on the probability that a given patient's condition will have a response and the time of onset of that response. Because infection is the major cause of death in patients with mycosis fungoides/Sézary syndrome, preservation of cellular immune function is desirable.
- Topical treatments: Generally, use topical steroids, topical retinoids, topical chemotherapy (eg, nitrogen mustard or bischloroethylnitrosourea [BCNU]), ultraviolet B (UV-B) light or UV-A light treatment enhanced with psoralen (PUVA), or total body electron beam radiation in the patch or plaque phase. These modalities are also used in the tumor phase combined with systemic modalities (eg, PUVA plus interferon).
- Systemic treatment: Examples include the following:
- Extracorporeal photopheresis (leukapheresis with PUVA treatment for the collected white blood cells, with reinfusion of treated cells)
- Recombinant alfa interferon
- Oral retinoids
- Fusion toxin treatment
- Histone deacetylase inhibitor treatment
- Monoclonal antibody treatment
- Systemic chemotherapy with a variety of single agents
- Combination chemotherapy: This is generally not used because the infectious complications and short response duration outweigh the modest response rates (compared with other non-Hodgkin lymphomas). Increased survival is not demonstrated with the use of combination chemotherapy relative to sequential topical agents.
- Bone marrow transplantation22 : Allogenic transplants are reported in the literature as case reports or small groups of patients. A German study suggests that "in young patients with a treatment-refractory course of mycosis fungoides, allogeneic stem cell transplantation" may be an important alternative option to manage mycosis fungoides because "complete clinical remission can be obtained even in advanced stages."3
Consultations
- Dermatologist
- Medical oncologist
- Radiation oncologist
Diet
No special diet is required for patients with mycosis fungoides.
Activity
No restrictions on activity are required for patients with mycosis fungoides.
Medication
Topical mycosis fungoides treatments, such as topical steroids, topical retinoids, topical chemotherapy, and light treatment that may be enhanced by the ingestion of psoralen, are used to induce remissions, which may be lengthy in patients whose disease is largely confined to the skin. Systemic treatment, such as oral retinoids, interferon, fusion toxins, monoclonal antibodies, and single-agent chemotherapy, can be used sequentially to palliate symptoms from more advanced mycosis fungoides.
Antipruritics
Nonspecific antipruritic treatments used to control symptoms are useful and often necessary adjuncts to more specific therapies.
Doxepin capsules, doxepin cream 5% (Zonalon, Sinequan, Adapin)
Inhibits histamine release, which in turn reduces pruritus.
Adult
25-75 mg PO qhs
Alternatively, apply topically as a cream sparingly on a limited area of skin.
Pediatric
Not established
Decreases the antihypertensive effects of clonidine but increases the effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin, carbamazepine, and barbiturates.
Documented hypersensitivity; urinary retention; acute recovery phase following myocardial infarction; glaucoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in the presence of cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism and in patients receiving thyroid replacement therapy.
Topical Steroids
A majority of patients with the patch phase will respond, usually to class I (highest potency) steroids. Steroids lyse T lymphocytes and block cytokine secretion.
Clobetasol cream (Temovate) 0.05%
Class I superpotent topical steroid. Suppresses mitosis and increases the synthesis of proteins that decrease inflammation and cause vasoconstriction.
Adult
Apply topically bid to affected areas
Pediatric
Not established
None reported
Documented hypersensitivity; viral or fungal skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use on the face, groin, or axillae; systemic absorption can produce adrenal suppression; may suppress adrenal function in prolonged therapy
Topical Chemotherapy Agents
Topical chemotherapy agents inhibit cell growth and proliferation. Most cases of patch or plaque phase disease will respond (complete response rate 60%).
Nitrogen mustard (Mustargen)
Cytotoxic to cancer cells via DNA alkylation, but topical preparations may succeed via immunogenic mechanism because the drug does not appear to be absorbed systemically. May be mixed by patient 10 mg/40-60 mL tap water and painted on the body. Also available as an ointment mixed by a pharmacist at 10 mg% in Aquaphor.
Adult
Apply from the neck down, sparing the genitals, qd until complete response, and then taper use.
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Delayed hypersensitivity (35-60%) can be overcome with the use of topical steroids or desensitization; less common with use of ointment; associated with an increased risk of nonmelanoma skin cancers
Psoralens
Psoralens inhibit DNA synthesis in tissues exposed to psoralen and UV-A. Most cases of patch or plaque phase disease (76-90% complete responses) will respond when psoralen is combined with UV-A exposure (PUVA).
Methoxsalen (Oxsoralen-Ultra, Uvadex injection)
Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UVA.
Adult
Oxsoralen ultra: 10 mg PO in dose per weight 1.5-2 h before UV-A exposure
Uvadex: During each photopheresis treatment performed, 10 mL (200 mcg) of methoxsalen is injected directly into the photoactivation bag during the first buffy coat collection cycle; at the end of 6 cycles, a total of 740 mL (240 mL of buffy coat, 300 mL of plasma, and 200 mL of isotonic sodium chloride priming fluid) is collected and mixed with 200 mcg of methoxsalen present in the photoactivation bag; after photoactivation, the cells are reinfused; administer methoxsalen on 2 consecutive days q4wk for a minimum of 7 treatment cycles (6 mo).
Pediatric
Not established
Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamides
Documented hypersensitivity; light-sensitive disease states (eg, lupus, porphyria); history of melanoma; hepatic disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patient should wear UV-A–absorbing, wrap-around sunglasses during daylight for 24 h after drug ingestion to prevent cataracts; patients should receive eye examinations yearly; ensure that male genitalia are shielded during treatment unless affected; avoid sun exposure for 48 h after treatment; carefully monitor patients for development of skin cancer, including melanoma.
Biologic Response Modifiers
Biologic response modifiers may inhibit the proliferative capacity of malignant T cells by modulating cytokine production, and they may also enhance the antitumor immune response by augmenting cell-mediated cytotoxicity.
Recombinant alfa interferon (Intron-A, Roferon-A)
Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Adult
Dose and frequency not determined; may initiate treatment with 3 million U 3 times/wk; increase prn to obtain desired response or as patient tolerates
Pediatric
Not established
Theophylline may increase interferon alfa toxicity; cimetidine may increase the antitumor effects; zidovudine and vinblastine may increase the toxicity of interferon alfa
Documented hypersensitivity; history of cardiovascular disease; preexisting psychiatric condition, especially depression or history of severe psychiatric disorder; patients with preexisting thyroid abnormality whose thyroid function cannot be maintained in the reference range by medication
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Because of fever and other flulike symptoms associated with recombinant alfa interferon, use the drug cautiously in patients with other debilitating medical conditions (eg, pulmonary disease, diabetes); caution patients about performing tasks that require complete mental alertness (such as operating machinery or driving a motor vehicle) if they are experiencing severe fatigue; closely monitor any patient who develops liver function abnormalities during treatment and, if appropriate, discontinue treatment; variations in dose, routes of administration, and adverse reactions may exist among different brands of interferon; therefore, do not use different brands in any single treatment regimen.
Retinoids
Retinoids are vitamin A analogues involved in the modulation of cell growth, division, reproduction, and differentiation.23 Their biologic effects result from alterations in gene expressions that are mediated through 2 major types of nuclear receptors, the retinoic acid receptor (RAR) and the retinoic X receptor (RXR). Each receptor subtype likely controls the expression of both unique and common genes. Subclass-specific retinoids are available.
Bexarotene (Targretin)
An X-receptor–specific retinoid. May inhibit sebaceous gland differentiation and abnormal keratinization. Has been demonstrated in vivo to enhance apoptosis of cells, as well as upregulate the alpha and beta subunits of IL2 receptor.
Adult
300 mg/m2/d PO single dose with meal
Pediatric
Not established
On the basis of metabolism of bexarotene by cytochrome P-450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P450 3A4 may increase serum bexarotene levels; rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P-450 3A4 may reduce plasma bexarotene levels; caution when administering bexarotene to patients using insulin, agents enhancing insulin secretion, or insulin sensitizers, because bexarotene could enhance their action.
Documented hypersensitivity; uncontrolled hyperlipidemia or hypothyroidism before drug initiation; patients with risk factors for pancreatitis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
When used in women of childbearing potential, obtain a negative pregnancy test result 1 wk before therapy and monthly thereafter; instruct women of childbearing potential to use 2 reliable forms of contraception simultaneously (unless abstinence is the chosen method of contraception) for 1 month before therapy, during therapy, and 1 month following discontinuation of the drug; instruct male patients with sexual partners who are pregnant or who have childbearing potential to use condoms during sexual intercourse while taking the drug and for 1 mo afterward; perform fasting blood lipid determinations before the therapy is initiated and weekly until the lipid response to the drug is established; obtain and serially monitor baseline CBC counts, liver function, and thyroid function tests; advise patients to limit vitamin A supplements and to minimize exposure to sunlight and artificial UV light.
Fusion Toxins
Recombinant toxins are generated by fusion of a plant or bacterial toxin gene to a receptor ligand. The first such toxin to enter clinical trial was DAB-IL2.
Denileukin diftitox (Ontak)
A molecule in which the diphtheria toxin and the receptor-binding domain of human interleukin 2 (IL-2) are fused. Targets cells by binding to medium- and high-affinity IL-2 receptors. Then, it is internalized by receptor-mediated endocytosis, inhibiting protein synthesis by toxin-mediated ADP ribosylation of elongation factor 2. About 50% of patients with MF or SS have malignant cells that express CD25. When the drug was administered to heavily pretreated patients with mycosis fungoides or Sézary syndrome who had CD25 expression in at least 20% of their malignant cells, a 30% overall response occurred.
Adult
9 or 18 mcg/kg/d IVPB for 5 consecutive d q21d infused over 45-60 min
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Ensure that drugs for the treatment of acute hypersensitivity reactions and resuscitative equipment are readily available during administration; carefully monitor weight, edema, blood pressure, and serum albumin levels on an outpatient basis; check CBC counts, blood chemistries (eg, liver, renal function, serum albumin) before the initiation of drug and qwk during therapy; delay administration until the serum albumin level is at least 3 g/dL; take special care in patients with preexisting cardiovascular disease.
Histone Deacetylase Inhibitors
Histone deacetylase inhibitors may inhibit gene transcription.
Vorinostat (Zolinza)
Histone deacetylase (HDAC) inhibitor. HDAC inhibition results in hypoacetylation of core nucleosomal histones, condenses chromatin structure, and represses gene transcription. Indicated for treatment of progressive, persistent, or recurrent cutaneous T-cell lymphoma.
Adult
400 mg PO qd with food; if intolerant to therapy, may decrease dose to 300 mg PO qd; if necessary, further reduce to 300 mg PO qd for 5 consecutive days qwk
Pediatric
Not established
Coadministration with other HDAC inhibitors (eg, valproic acid) has caused severe thrombocytopenia and GI bleeding; coadministration with warfarin prolongs PT duration and INR.
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include diarrhea, nausea, anorexia, weight loss, vomiting, and constipation (antiemetics, antidiarrheals, or fluid and electrolyte replacement may be required to prevent dehydration); also commonly causes fatigue or chills; pulmonary embolism and deep vein thrombosis have been reported; dose-related thrombocytopenia and anemia have occurred (may require dose reduction or discontinuance); may cause hyperglycemia; data are limited on the effect on QTc (monitor potassium, magnesium, and calcium levels and perform periodic ECGs); data are limited in patients with renal or hepatic insufficiency
Systemic Chemotherapy Agents
Many active agents, including antimetabolites, alkylating agents, topoisomerase II inhibitors, anthracyclines, and purine analogues exist. The most extensive data exist for the use of methotrexate.
Methotrexate (Folex PFS, Rheumatrex)
Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response is observed in 3-6 wk following administration.
Adult
5-10 mg PO q1wk; not to exceed 90 mg; doses higher than 25 mg are best administered IVPB
Pediatric
Not established
NSAIDs and salicylates may reduce excretion; toxicity may be increased with concomitant use of phenytoin due to displacement from serum albumin; renal clearance of methotrexate may be reduced by probenecid and penicillin; may decrease the clearance of theophylline
Documented hypersensitivity; do not administer to patients with known liver disease; patients with impaired renal function, ascites, pleural effusion, or significant edema can experience reduced elimination and require careful monitoring
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Pulmonary symptoms require immediate evaluation; diarrhea and mucositis require interruption of therapy.
More on Mycosis Fungoides |
| Overview: Mycosis Fungoides |
| Differential Diagnoses & Workup: Mycosis Fungoides |
 Treatment & Medication: Mycosis Fungoides |
| Follow-up: Mycosis Fungoides |
| Multimedia: Mycosis Fungoides |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Hoff NP, Groffik A, Mota R, et al. [Successful use of allogeneic stem cell transplantation for treatment-refractory mycosis fungoides] [German]. Hautarzt. Oct 2008;59(10):779-82. [Medline].
Rook AH, Yoo EK, Grossman DJ, et al. Use of biological response modifiers in the treatment of cutaneous T-cell lymphoma. Curr Opin Oncol. Mar 1998;10(2):170-4. [Medline].
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Further Reading
Related eMedicine Topics
- Cutaneous T-Cell Lymphoma [in the Dermatology section]
- Erythroderma (Generalized Exfoliative Dermatitis) [in the Dermatology section]
- Heart-Lung Transplantation [in the Transplantation section]
- Lymphoma, Cutaneous T-Cell [in the Hematology section]
- Staphylococcus Aureus Infection [in the Pediatrics: General Medicine section]
Clinical Trials
- Photopheresis as an Interventional Therapy for the Treatment of CTCL (Cutaneous T-Cell Lymphoma, Mycosis Fungoides) Stage 1A, 1B, 2A
- Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides
- Study of Alemtuzumab to Treat Advanced Mycosis Fungoides/Sezary Syndrome
- Improving outcomes for people with skin tumours including melanoma. National Collaborating Centre for Cancer - National Government Agency [Non-U.S.]. 2006 Feb. 174 pages. NGC:004876
Keywords
mycosis fungoides, MF, cutaneous T-cell lymphoma, CTCL, malignant T-cell lymphoma of the skin, Sézary syndrome, SS, pagetoid reticulosis, erythroderma, malignant lymphoma, skin lesions, Staphylococcus aureus, , Pseudomonas aeruginosa, , non-Hodgkin lymphoma, non-Hodgkin's Lymphoma, NHL
