Skin-Directed Therapies

This piece was written by Guide Contributors

Patients with cutaneous T-cell lymphoma (CTCL) who have early-stage disease can be treated effectively with skin-directed therapies.3 Skin-directed treatments for CTCL include topical therapies like topical steroids, phototherapy, and radiation. Topical treatments are applied to the skin directly and are mostly active on the surface of the skin, without much absorption into the bloodstream. This can limit side effects. Patients can often use skin-directed therapies for a long time.4,5 Although the disease will probably come back (relapse), the same treatment that worked previously often works again. Skin-directed therapies are recommended alone or in combination for treating mycosis fungoides and other early-stage CTCLs. 

CUTANEOUS T- CELL LYMPHOMA TREATMENT: EARLY STAGE

EXPERT PRESENTER

Alain H. Rook, MD, Professor of Dermatology, University of Pennsylvania, Perelman School of Medicine

Topical Corticosteroids

Topical corticosteroids (sometimes referred to simply as steroids) are one of the more established treatments for CTCL. These agents cause the immune system to become more active and also have anti-inflammatory effects. There are many options in steroid treatment, and multiple formulations are available including creams, gels, ointments, and lotions. With modest efficacy,8,9 steroids can be particularly useful in reaching some areas of the skin that are more difficult to reach with other forms of treatment, such as under the arms. They are also helpful in alleviating symptoms of itching.

However, steroids are associated with several side effects such as thinning of the skin (atrophy), stretch marks/striae (irregular areas of skin that look like bands, stripes, or lines), acne/pimples, and hair growth, which should be considered when evaluating this option. Although they may be used independently, steroids are frequently used in combination with other treatments.  

Topical Chemotherapy

Alkylating agents are a class of chemotherapy that act by chemically modifying DNA and preventing cancer cells from growing. Mechlorethamine (Mustargen® and Valchlor™), commonly known as nitrogen mustard, and carmustine (BiCNU®) are examples of these. They have been mixed into solution or compounded into ointments and used topically to treat CTCL.10-12 Recently, a gel form of mechlorethamine (Valchlor™) has become available for treatment of CTCL.

During the course of topical chemotherapy, patients sometimes experience redness, irritation, and/or allergy (dermatitis), development of fine, dilated blood vessels (telangiectasias), or darkening of the skin (hyperpigmentation) in the treated area. Dermatitis and hyperpigmentation may cause physicians and patients to choose another treatment when the affected area is visual, such as the face. 

Imiquimod

Topical imiquimod (Aldara®) is a cream that works by stimulating the release of interferon and cytokines, which have anti-tumoral effects.13 While the exact mechanism behind the anti-tumoral response is still unclear, imiquimod is thought to stimulate dendritic cells, which leads to immune activation. Although large clinical trials are needed, there is mounting evidence from clinical practice that imiquimod has activity against CTCL. In most cases reported to date, imiquimod was used for patients who had failed at least one other topical therapy, suggesting imiquimod may be beneficial in disease for which the initial treatment has stopped working (resistant or refractory disease).14,15 

One current limitation is that this cream is distributed in small packets, making it difficult to use over larger areas of the body.

Retinoids

Retinoids are another, newer class of agents that are available as topical or oral formulations, which include bexarotene (Targretin®) and tazarotene gel (Tazorac®). These vitamin A-derived agents regulate a wide range of biological processes, including cell growth and death.16 Retinoids have been shown to be effective at killing cancer cells and inhibit the ability of cancer cells to move into the skin, which helps with itching and redness.17 Topical bexarotene is approved by the US Food and Drug Administration (FDA) for the treatment of Stage 1A and 1B CTCL in patients who have not responded to or tolerated other therapies.18 There are also oral forms available (see Systemic Therapies).

Common side effects with the topical form of bexarotene include redness, itching, warmth of the skin, swelling, burning, scaling, and other skin irritations. The treated areas should also be protected from prolonged exposure to sunlight or other sources of ultraviolet (UV) light, such as tanning lamps.

What are the differences between PUVA, UVB and Narrow Band UVB light treatments?

EXPERT PRESENTER

Christiane Querfeld, MD, PhD, Dermatologist/Dermapathologist, City of Hope National Medical Center (At time of publication: Memorial Sloan Kettering)

Radiation Therapy
Radiation Therapy

Radiation Therapy

Radiation therapy is considered the most effective single treatment for primary cutaneous lymphoma.25,26 Advances in radiation therapy have led to the use of low-energy orthovoltage X-rays and electron beam radiotherapy. Orthovoltage X-rays can successfully treat recurrent lesions; however, these rays will also penetrate and damage the underlying tissues, such as blood vessels, muscles, and bone marrow. Local radiation therapy is typically used for patients with limited extent tumors (T3) with or without patches and/or plaques. 

Total Skin Electron Beam

Total skin electron beam (TSEB) therapy is a type of radiation therapy that has shown high response rates, particularly in early-stage disease.27-31 Patients usually receive only one TSEB treatment. However, repeat treatments after disease relapse are possible when other therapies have failed. This treatment penetrates only the superficial portions of the skin, limiting damage to underlying tissues.

This is a complicated treatment that requires a skilled multidisciplinary team of oncologists, physicists, radiographers, nurses, and dermatologists experienced in the management of cutaneous lymphoma. There are also risks including infection, blisters, skin discoloration, and pain.32 TSEB therapy is commonly used in combination with chemotherapy.33-35

Brachytherapy

Brachytherapy, also known as internal radiotherapy, is a newer method for delivering radiation in cancer treatment. The term “brachy” is from the Greek word “brachys,” meaning short distance. Very small radioactive seeds or sources called implants are placed in or near the tumor by computer-controlled delivery through a thin plastic catheter or metal tube called an applicator. The implants are about the size of a grain of rice. A computer controls where the seeds are delivered and how long they remain in any location. They are located so as to harm as few healthy cells as possible. The radioactive material may be left for a short time or more permanently. The applicator may be left until all treatments are completed. The procedure, which is done in a hospital operating room, may only last a few minutes.

Locating the radiation source so close to the cancerous tissue helps to spare surrounding healthy tissue from radiation exposure. Short-range radiation sources are used. It can be used alone or in combination with other therapies such as surgery, external beam radiotherapy, or chemotherapy. One trial investigating the use of brachytherapy in the treatment of patients with mycosis fungoides analyzed 23 facial lesions in 10 patients. This trial reported dramatic clinical improvement and no recurrences in these patients during the 6.3-month follow-up period; however, longer-term follow-up is still needed.36 

 

Link to References used on page.

Radiation Therapy
Q&A Session followed presentation with topics including:
- Is it usual to follow total skin electron beam therapy with systemic chemotherapy?
- How might facial lesions be treated?
- How frequently can total skin electron beam therapy be repeated?
- How frequently can localized electron beam therapy be repeated?
- Can radiation be used on open lesions or lesions that are not healing?
- Romidepsin, dose reduction and Sezary Syndrome
- Recurrence of lesions and type and length of treatment
- Effectiveness of Doxil in treating cutaneous lymphoma
- What determines how actively "clear" skin may be pursued?
- What treatment can safely be used around the eyes?

EXPERT PRESENTER

John O'Malley, MD, PhD, Harvard Medical School, Brigham and Women’s Hospital

Learn More

Fertility

Couple with physician
When it comes to family planning, using even mild therapies for a long period of time can be an issue. Because many therapies only work while they are being given, aspects of family planning often need to be considered when choosing a therapy.

Staging Cutaneous T-cell Lymphoma

Staging describes how much of the body is affected by cutaneous lymphoma and where. Identifying your stage is important in determining appropriate treatment.
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