04 Malignant Skin Lesions

04 Malignant Skin Lesions

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Unformatted text preview: combination regimens—including BOLD (bleomycin, vincristine, lomustine [CCNU], DTIC), CVT (cisplatin, vincristine, DTIC), and CBDT (cisplatin, carmustine [BCNU], DTIC, tamoxifen)—have been employed, with response rates ranging from 9% to 55%.72 The oral alkylating agent temozolamide has been studied in stage IV melanoma patients; compared with DTIC, it yields a modest prolongation of survival, with an acceptable side-effect profile.73 Melanoma vaccines. Several experimental melanoma vaccines are being investigated for possible use in advanced-stage melanoma. These agents use a variety of modalities to present melanoma antigens to host immune cells in an immunostimulatory context.74-76 There was considerable initial optimism regarding this approach, but a 2004 review of the experience at the National Cancer Institute found that the response rate for cancer vaccines was only 2.6%77 (a figure comparable to the results obtained by others). The authors concluded that the use of cancer vaccines may still prove to be a viable strategy, but profound changes will be required to enhance the efficacy of these agents. Immunotherapy. At present, immunotherapy is perhaps the most promising area of investigation with respect to the treatment of advanced melanoma. Immunotherapy has been defined in various ways, but in general, it can be thought of as a form of treatment based on the concept of modulating the immune system to achieve a therapeutic goal.78 There are several different modalities that can be considered immunotherapy, including monoclonal antibody therapy and interferon-based therapy. For present purposes, we will focus on two modalities that are currently under active investigation: highdose interleukin-2 (IL-2) therapy and adoptive cell transfer. In initial studies, the response rates after high-dose IL-2 therapy for melanoma have ranged from 15% to 20%, with about half of the responding patients experiencing complete regression.79 In those patients who do achieve a complete response, the effect is often durable.80 Unfortunately, IL-2 immunotherapy is associated with severe side effects. Adoptive cell transfer involves the administration of activated cytotoxic T lymphocytes (CTLs) that are generated against specific tumor types.These CTLs can be generated either by using specific tumor-associated antigens or by culturing lymphocytes with tumor cells.The objective is to encourage the selection of tumor-specific T lymphocytes that are capable of generating a strong immunologic response and thereby help break the body’s immunologic tolerance of the tumor. Unfortunately, initial clinical trials of activated T cell transfer for other types of malignancy found that the transferred cells did not remain present in sufficient concentrations to yield a significant clinical effect.81 However, the addition of nonmyeloablative lymphodepleting chemotherapy, followed by autologous transfer of tumor-specific CTLs in conjunction with IL-2 administration, was shown to result in rapid clonal...
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This note was uploaded on 03/21/2011 for the course ONC 01 taught by Professor Dzodic during the Spring '11 term at Multimedia University, Cyberjaya.

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