IMMUNOMODULATING
AGENTS
Levamisole (Ergamisol) is an antiparasitic drug that
has been found to enhance T-cell function and cellular im-munity. The drug
improves survival of patients with re-sected colorectal cancers when combined
with 5-fluo-rouracil; the mechanism of this interaction is not known.
Levamisole does not have antitumor activity against established or metastatic
cancer and has not been found useful in the adjuvant therapy of cancers other
than colorectal cancer.
The major adverse effects of
levamisole are nausea and anorexia. Skin rashes, itching, flulike symptoms, and
fevers also have been observed.
Interferon alfa-2b (Intron A) is a recombinant DNA product
derived from the interferon alfa-2b gene of hu-man white blood cells. Its
mechanism of antitumor ac-tion involves binding to a plasma membrane receptor
but is otherwise poorly understood. Its serum half-life is 2 to 3 hours after
parenteral administration.
Interferon alfa-2b is useful
in the treatment of a rare form of chronic leukemia, hairy cell leukemia, in
which it produces remissions in 60 to 80% of patients. How-ever, it has minimal
antitumor activity in most human cancers. Remissions lasting a few months have
been ob-served in 10 to 20% of patients with lymphomas, multi-ple myeloma,
melanoma, renal cell carcinoma, and ovarian carcinoma.
The adverse effects of
interferon alfa-2b include fever and a flulike syndrome of muscle ache,
fatigue, headache, anorexia, and nausea. Other less common side effects
in-clude leukopenia, diarrhea, dizziness, and skin rash.
Aldesleukin (IL-2, Proleukin) is a human recombinant
interleukin-2 protein. Its antitumor action is thought to include multiple
effects on the immune system, such as enhancement of T-lymphocyte cytotoxicity,
induction of natural killer cell activity, and induction of
interferon-production. Aldesleukin has been used alone and in combination with
lymphokine activated killer (LAK) cells or tumor-infiltrating lymphocytes
(TIL).
The drug produces remissions
in 15% of patients with renal cell carcinoma, with median durations of
re-mission of 18 to 24 months.
Several serious toxicities
have been observed, with a fatality rate of 5% in the initial studies. The
major ad-verse effect is severe hypotension in as many as 85% of patients,
which may lead to myocardial infarctions, pul-monary edema, and strokes. This
hypotension is thought to be due to a capillary leak syndrome resulting from
extravasation of plasma proteins and fluid into ex-travascular space and a loss
of vascular tone. Patients with significant cardiac, pulmonary, renal, hepatic,
or CNS conditions should not receive therapy with aldesleukin. Other adverse
reactions include nausea and vomiting, diarrhea, stomatitis, anorexia, altered
mental status, fevers, and fatigue.
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