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1686 Part XI: Malignant Lymphoid Diseases Chapter 103: Cutaneous T-Cell Lymphoma (Mycosis Fungoides and Sézary Syndrome) 1687

cells. Complete responses of 20 percent and overall responses of 60 surface (total skin electron beam therapy [TSEBT]). It delivers a uni-
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percent are reported. 89,90 It is applied in a thin layer to the patches and form dose from the surface to a specific depth, after which the dose
plaques twice daily. The major toxicity is irritation at the site. Oral falls off rapidly, sparing deeper normal tissues. It is usually delivered to
administration of bexarotene is associated with severe birth defects. penetrate only into the dermis, systemic effects are minimal, and the
Considering potential absorption of the drug from the skin surface, complete remission rate is 80 percent. 3,103,104 Twenty percent of patients
bexarotene should not be given to pregnant women. remain relapse free after 3 years. The relapse rate depends on the stage
Phototherapy Phototherapy is a well-established effective treat- of the disease, and the relapse usually is short lived (may be as short as
ment for MF, utilizing ultraviolet radiation of the UVA and UVB spectra. 2 to 3 weeks) in patients with erythroderma or numerous tumors. In
It is not FDA-approved for treatment of MF and SS because of a lack of the past, the treatment regimen was 4 Gy per week to a total dose of
prospective clinical trials, but is considered to be one of the most effective 36 Gy in 8 to 9 weeks. However, low-dose electron beam therapy has
therapies for early disease (mainly patches and thin plaques). Photother- been shown to be nearly as effective, eliminating the usual side effects,
apy may result in complete clearing of the lesions. It was hypothesized such as alopecia, skin atrophy, destruction of skin adnexa, dermatitis,
that the mechanism of action of this therapy is Langerhans’ cells deple- and increased risk of cutaneous malignancy. 105–108 The advantage of elec-
tion from the epidermis. 91 tron beam therapy is the high frequency of durable complete responses
The peak of therapeutic effectiveness of UVB is within 295 without systemic toxicity. Up to three courses of electron beam therapy
to 313 nm. Conventional broad band UVB lamps emit wavelengths can be safely administered when used in a highly fractionated fashion
ranging from 280 to 330 nm, but narrow band UVB (NBUVB) emits (1 Gy per dose).
only wavelengths 311 to 312 nm, eliminating harmful UV rays below Imiquimod (Aldara) Imiquimod is a topical immunomodulator
300 nm, which can cause erythema or severe burning and increase the that is extremely effective in the treatment of condylomata acuminata,
risk of skin cancer. 92–94 Similarly, excimer lasers emitting at 308 nm actinic keratoses, basal cell carcinomas, keratoacanthomas, and other
can be successfully used for hard to reach areas resistant to other ther- cutaneous malignancies. The mode of action is not known but is thought
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apy. NBUVB may be a viable alternative to psoralen with UVA radi- to be related to induction of tumor necrosis factor-α and interferons
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ation (PUVA) with similar response rates in a small cohort. Therapy resulting in activation of a Th1-type immune response and rejection of
should be instituted three times per week. On average, 6 to 12 weeks cancer or virally infected cells. Several groups reported the effectiveness
are required to achieve response. Maintenance therapy is required after of imiquimod in early patch MF. 109,110 It should be used three times per
a response occurs for at least 2 more months, but thereafter the main- week for 3 months. It is not FDA-approved for therapy of MF and SS.
tenance regimen for various light sources is not well established and
depends on the personal experience of the treating physician.
The UVA spectrum ranges from 320 to 400 nm, therefore UVA light SYSTEMIC THERAPY
penetrates deeper than UVB, into the dermis. Phototherapy involving Oral Retinoids
UVA radiation is used with psoralen and is referred to as PUVA. Pso- Bexarotene (Targretin) is an FDA-approved RXR-selective retinoid,
ralen is a phototoxic furocoumarin activated by UVA light. In its active or “rexinoid,” for therapy of the MF. It is a first-line systemic agent
form, psoralen bonds covalently and irreversibly to DNA. Therefore, for patients without contraindications to retinoids. At the currently
psoralen activated by UVA light affects cells primarily in the epidermis FDA-approved dose of 300 mg/m /day the overall response rate to bex-
2
and papillary dermis. A 60 percent complete remission rate and long- arotene monotherapy ranges from 45 to 57 percent with at least 2 per-
term remissions (>10 years) have been reported with PUVA; patients cent complete responses. 111,112 Higher doses are associated with higher
with generalized erythroderma and tumors have lower response rates response rates and shorter time to response, but also with a higher
than patients with plaques. 97–99 Psoralen usually is given at a dose of incidence of adverse events. All patients on bexarotene rapidly develop
0.6 mg/kg orally, 2 hours before the UVA light therapy. Treatments ini- central hypothyroidism and hyperlipidemia (most significantly hyper-
tially are given three times per week. Maintenance therapy may be given triglyceridemia), requiring coadministration of thyroid supplements
every 2 to 4 weeks for an indefinite period. Adverse effects of PUVA and lipid-lowering agents. Other rare adverse events include headaches,
therapy include mild nausea, pruritus, and sunburn-like changes, with possibly a result of pseudotumor cerebri, leucopenia, and pruritus. The
atrophy and dry skin. PUVA is not cross-resistant with other treatment majority of side effects are laboratory findings and dose-dependent;
modalities. Disadvantages of PUVA therapy are its necessity to visit bexarotene is usually well tolerated by the patients. Its use is recom-
doctor’s office frequently (from three times a week to once a month) mended beginning with refractory or persistent stage IA disease as well
and its expense. Long-term side effects include an increased incidence as in more advanced stages (NCCN guidelines). Standard procedures
of skin cancers and melanoma. 100 for management of patients on bexarotene therapy are reviewed.
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Photodynamic Therapy Photodynamic therapy is a photochem- Bexarotene is safe to use long-term for maintenance therapy. Bexaro-
otherapy that utilizes two properties of porphyrins: their selective accu- tene and other retinoids are labeled pregnancy Category X, and must
mulation in tumor sites (e.g., 5-aminolevulinic acid) and their ability not be given to a pregnant woman or a woman who intends to become
to generate cytotoxic oxygen species at the tumor site after red-light pregnant.
irradiation. 5-Aminolevulinic acid is a natural porphyrin precursor and Other retinoids have been used for treatment of MF and SS, includ-
upon irradiation is converted in the tumor to the highly photoactive ing isotretinoin, acitretin, etretinate (not available in United States), and
endogenous protoporphyrin IX. Red-light irradiation is safe and pene- all-trans retinoic acid (ATRA). Activity of these compounds in MF/SS
trates deep in the tissue, allowing for treatment of thick tumors. Photo- has been demonstrated in case series or small open-label pilot studies,
dynamic therapy is especially useful in patients with limited skin area but there are no prospective studies formally evaluating these drugs. 114
involved by few tumors. The main problem with the treatment is that Histone Deacetylase Inhibitors Vorinostat is an oral histone
the pain induced during irradiation limits its use for larger areas. 101,102 It deacetylase inhibitor (HDACi), which was FDA-approved for treat-
is used for therapy of MF off-label. ment of cutaneous manifestations of recurrent, refractory or persistent
Electron Beam Therapy Electron beam therapy is a highly effec- MF and SS in 2008 at the dose of 400 mg by mouth daily. Vorinostat
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tive form of treatment of MF and can be used as a localized therapy was evaluated in an open-label phase IIb clinical trial and was shown
(LEBT) to specific sites or lesions, or as radiation of the entire skin to have an overall response rate of 30 percent. No complete responses

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