Chapter: Modern Pharmacology with Clinical Applications: Antineoplastic Agents

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Immunomodulating Agents

Levamisole (Ergamisol) is an antiparasitic drug that has been found to enhance T-cell function and cellular im-munity.

IMMUNOMODULATING AGENTS

 

Levamisole

 

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

 

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.

Interleukins

Aldesleukin

 

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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