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Chapter: Clinical Pharmacology: Antineoplastic drugs

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Monoclonal antibodies

Recombinant DNA technology has allowed for the development of monoclonal antibodies directed at such targets as other immunecells or cancer cells.

Monoclonal antibodies

Recombinant DNA technology has allowed for the development of monoclonal antibodies directed at such targets as other immunecells or cancer cells. Monoclonal antibodies include:

·                 alemtuzumab

 

·                 gemtuzumab ozogamicin

 

·                 ibritumomab tiuxetan

 

·                 rituximab

 

·                 trastuzumab.

 

Pharmacokinetics

Because of their large protein molecule structure, monoclonal an-tibodies aren’t absorbed orally. They may have a limited distribu-tion as well as a long half-life, sometimes measured in weeks.

Pharmacodynamics

 

Monoclonal antibodies bind to target receptors or cancer cells and cause tumor death via several mechanisms: They may induce pro-grammed cell death; they may recruit other elements of the im-mune system to attack the cancer cell; or they may deliver a dose of a toxic chemotherapy drug (gemtuzumab) or radiation (ibritu-momab) to the tumor site.

Pharmacotherapeutics

 

Monoclonal antibodies have demonstrated activity in both solid tumors and hematologic malignancies, such as:

 

§    non-Hodgkin’s lymphoma—rituximab and ibritumomab (target CD20 or malignant B lymphocytes)

 

§    chronic lymphocytic leukemia—alemtuzumab (target CD52 antigen or B cells)

 

§    acute myeloid leukemia—gemtuzumab (target CD33 antigen in myeloid leukemic cells)

 

§    breast cancer—trastuzumab (target HER-2 protein in breast cancer cells).

Drug interactions

Although no interactions have been noted with alemtuzumab, mul-tiple drug interactions are associated with other monoclonal anti-bodies.

·               Ibritumomab may interfere with the actions of such drugs as warfarin, aspirin, clopidogrel, ticlopidine, nonsteroidal anti-inflammatory drugs, azathioprine, cyclosporine, and corticoste-roids.

 

·                 Trastuzumab increases the cardiac toxicity associated with an-thracycline administration. (See Adverse reactions to monoclonalantibodies.)

 

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