Cancer Health Center

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Another approach using anti-inflammatory agents (pioglitazone and rofecoxib) coupled with trofosfamide in a specific timed sequence was successful in two patients with disease resistant to standard chemotherapy treatment.[9]

Treatment of single-system skin disease

• Localized lesions can be treated by surgical excision, but as with bone, mutilating surgery, including hemivulvectomy, should be avoided unless the disease is refractory to available therapy.
• Topical therapies are described in greater detail in the childhood isolated skin involvement section of this summary and include topical or intralesional corticosteroid, topical tacrolimus, imiquimod, and psoralen and long-wave ultraviolet radiation (PUVA). Therapies such as PUVA may be more useful in adults where long-term toxicity may be less of a consideration.[10,11,12]
• Systemic therapy for severe skin LCH includes oral methotrexate, oral thalidomide, oral interferon-alpha, or combinations of interferon and thalidomide.[13,14] Recurrences after stopping treatment may occur but may respond to retreatment.
• Oral isotretinoin has achieved remission in some refractory cases of skin LCH in adults.[15]

Chemotherapy for the treatment of single-system and multisystem disease

Chemotherapy is generally used for skin LCH associated with multisystem disease in adults.

• Etoposide has been used with some success in single-system and multisystem LCH. Use of prolonged oral etoposide in adults with skin LCH has been reported with minimal toxicity, while 3-day courses of intravenous (IV) etoposide 100 mg/m² /day achieved complete remission in a small number of patients with resistant single-system and multisystem disease.[16] Another study at the same center found that azathioprine was the most successful drug for localized disease in adults with the addition of etoposide for refractory and multisystem disease.[17]
• For patients who do not respond to front-line therapy with etoposide, 2-CdA is effective for adults with skin, bone, lymph node, and probably pulmonary and central nervous system (CNS) disease.[18,19,20] The first study that used 2-CdA to treat refractory and recurrent disease reported on 16 patients with a median age of 44 years (range 19-72 years) who received one to six courses (median three courses) of 2-CdA at 0.14 mg/kg intravenously over 2 hours/day for 5 days. Most had localized disease: skin (n = 10), bone (n = 6), lung (n = 6), adenopathy (n = 5), or diabetes insipidus (n = 4). Complete response was seen in 44% of patients and partial response in 19% of patients for an overall response rate of 63%. Five of seven complete response patients remained in remission at 97.1 or more months. Leukopenia was the major toxicity seen in 50% of patients.[21,22]Three patients developed a second malignancy which may not be more than expected for this population group as five malignancies were found in 52 adult LCH patients in a series from Germany.[23] Similar to children, 2-CdA clearly has activity in single-system and low-risk multisystem disease but the number of courses should be limited in view of the potential for cumulative and sometimes long-lasting myelosuppression and immunosuppression. As discussed earlier, higher dose 2-CdA combined with high-dose cytosine arabinoside appears to be the best salvage protocol to date for refractory high-risk childhood LCH, but the combination, which requires acute myeloid leukemia-type supportive care, may be too toxic for elderly adults.
• An adult lymphoma treatment regimen, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin), was used in three patients with multisystem LCH and four with single-system multifocal bone LCH from 1995 to 2007.[24] Total duration of therapy was 12 weeks, response was seen in all patients, two with partial response and five with complete response. Three recurrences were seen after stopping therapy.[24] Despite the small number of patients and the retrospective nature of the study, MACOP-B may be useful as salvage therapy in adult patients with LCH and deserves further study.[25]
• Anecdotal reports have described the successful use of the bisphosphonate pamidronate in controlling severe bone pain in patients with multiple osteolytic lesions.[4,5,6]
• Imatinib mesylate has been effective in the treatment of four adult LCH patients who had skin, lung, bone, and/or CNS involvement.[26,27] Another adult LCH patient did not respond to imatinib mesylate.[28]