Chapter 083. Cancer of the Skin (Part 7)

Treatment of Metastatic DiseaseMelanoma can metastasize to any internal organ, the brain being a particularly common site. Metastatic melanoma is generally incurable, with survival in patients with visceral metastases generally
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Chapter 083. Cancer of the Skin (Part 7) Chapter 083. Cancer of the Skin (Part 7) Treatment of Metastatic Disease Melanoma can metastasize to any internal organ, the brain being aparticularly common site. Metastatic melanoma is generally incurable, withsurvival in patients with visceral metastases generally melphalan. High complete response rates have been reported, and responses areassociated with significant palliation of symptoms. A number of drugs and biological therapies have demonstrated minimalantitumor activity (15–20% partial response rates) in metastatic melanoma,including dacarbazine (DTIC); the nitrosoureas carmustine (BCNU), lomustine(CCNU), and semustine (methyl-CCNU); platinum analogues such as cisplatinand carboplatin; vinca alkaloids such as vincristine, vinblastine, and vindesine; thetaxanes paclitaxel and docetaxel; IFN-α; and interleukin 2 (IL-2). Althoughlimited in efficacy, single-agent dacarbazine is still considered the standardtreatment. Ongoing trials are attempting to define superior combinations. IL-2produces response rates similar to those seen with cytotoxic agents; however,active doses usually cause greater toxicity than chemotherapy. Response rates of>50% have been observed with IL-2 for intracutaneous and subcutaneous disease. Melanoma can express cell-surface antigens that may be recognized by hostimmune cells. These melanoma-associated antigens alone or in combination maymake it possible to develop vaccination strategies against melanoma. Suchstrategies include the use of purified tumor proteins as immunogens and the use ofgenetically altered tumor cells to elicit a T cell response. Alternative experimentalapproaches include efforts to expand tumor-specific T cells (either obtained fromthe tumor as tumor-infiltrating lymphocytes or harvested from the peripheral bloodafter vaccination) in vitro and transfer them into patients in large numbers. Inaddition, monoclonal antibodies to tumor antigens are being evaluated. Agentsdirected against the cell cycle pathways are also currently in trial. All of theseexperimental approaches will need considerable further development before beingapplicable on a wide scale. Advances in treating metastatic disease may also proveapplicable in the adjuvant setting. The absence of curative therapy for patients with metastatic melanomaunderscores the importance of early detection and prevention as strategies todecrease melanoma mortality. Patients with stage 4 melanoma are best treated bymedical oncologists with expertise in treating patients with advanced disease.Clinical trials should be considered as an option for this patient group. Nonmelanoma Skin Cancer Nonmelanoma skin cancer (NMSC) is the most common cancer in theUnited States, with an estimated annual incidence of >1.5 million cases. Basal cellcarcinomas (BCCs) account for 70–80% of NMSCs. Squamous cell carcinomas(SCCs), while representing only ~20% of NMSC, are more significant because oftheir ability to metastasize (Fig. 83-2); they account for most of the 2400 deathsannually. Incidence rates have risen dramatically over the past decade. Figure 83-2 Cutaneous neoplasms. A. Non-Hodgkins lymphoma involves the skinwith typical violaceous, plum-colored nodules. B. Squamous cell carcinoma isseen here as a hyperkeratotic crusted and somewhat eroded plaque on the lowerlip. Sun-exposed skin such as the head, neck, hands, and arms are other typicalsites of involvement. C. Actinic keratoses consists of hyperkeratotic erythematouspapules and patches on sun-exposed skin. They arise in middle-aged to olderadults and have some potential for malignant transformation. D. Metastaticcarcinoma to the skin is characterized by inflammatory, often ulcerated dermalnodules. E. Mycosis fungoides is a cutaneous T cell lymphoma, and plaque stagelesions are seen in this patient. F. Keratoacanthoma is a low-grade squamous cellcarcinoma that presents as an exophytic nodule with central keratinous debris. G.This basal cell carcinoma shows central ulceration and a pearly, rolled,telangiectatic tumor border.