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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.
- Spring '11
- The Land