Immune Therapies

Interferons

The categories of a, P and y interferons exist; the a interferons are used in the treatment of cancer. Interferon enhances the immune system's attack on cancer cells, can decrease new blood vessel formation, and can augment expression of antigen on tumor cell surfaces. Interferon has an elimination half-life of 3.7 to 8.5 hours. Interferon is filtered through the glomeruli and then degraded during tubular reabsorption. Interferon has shown clinical activity in the treatment of melanoma, kidney cancer, Kaposi's sarcoma, and chronic myelocytic and lymphocytic leukemia. Unfortunately, interferon is not well tolerated by patients because it causes a flu-like syndrome that consists of fevers and chills; depression, malaise, and fatigue are other side effects. Premedication with acetaminophen will help alleviate the flu-like symptoms, which will decrease with chronic administration.

Aldesleukin

Aldesleukin, commonly referred to as interleukin 2, is a lymphokine that promotes Band T-cell proliferation and triggers a cytokine cascade to attack the tumor. The phar-macokinetics are best described by a two-compartment model, with an a-half-life of 13 minutes and a terminal half-life of 85 minutes. Aldesleukin is eliminated by both glomerular filatration and peritubular extraction in the kidney. Aldesleukin has shown clinical activity in the treatment of kidney cancer and melanoma. Side effects of in-terleukin 2 vary by dose and route. IV high-dose interleukin 2 causes a drug-induced shock-like picture. Patients may develop hypotension despite aggressive IV hydration. Patients develop a red, itching skin; liver and kidney function tests change; fluid and electrolyte imbalances occur; and high fevers occur while receiving scheduled acetaminophen and nonsteroidal anti-inflammatory agents. Severe rigors and chills may require IV meperidine for symptom control. All the side effects reverse within 24 hours of stopping the drug. The toxicity profile is much less with subcutaneous admin istration. However, with subcutaneous administration, little nodules form at the injection site and may take months to resolve. Corticosteroids should not be administered to patients while receiving aldesleukin unless a life-threatening emergency should occur. Steroids will reverse all the symptoms and the antitumor effect, even with topical administration. The itching, red skin may be treated with topical creams and anti-histamines.

Denileukin Diftitox

Denileukin diftitox is a combination of the active sections of interleukin 2 and diphtheria toxin. It binds to high-affinity interleukin 2 receptors on the cancer cell (and other cells), and the toxin portion of the molecule inhibits protein synthesis to result in cell death. The pharmacokinetics of denileukin diftitox are best described by a two-compartment model, with an a-half-life of 2 to 5 minutes and a terminal half-life of 70 to 80 minutes. Denileukin diftitox is used for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 receptor. Side effects include vascular leak syndrome, fevers/chills, hypersensitivity reactions, hypotension, anorexia, diarrhea, and nausea and vomiting.

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