Clinical Pharmacology of Cancer Chemotherapeutic Drugs

CLINICAL PHARMACOLOGY OF CANCER CHEMOTHERAPEUTIC DRUGS

A thorough knowledge of the kinetics of tumor cell proliferation along with an understanding of the pharmacology and mechanism of action of cancer chemotherapeutic agents is important in designing optimal regimens for patients with cancer. The strategy for developing drug regimens also requires knowledge of the spe-cific characteristics of individual tumors. For example, is there a high growth fraction? Is there a high spontaneous cell death rate? Are most of the cells in G₀? Is a significant fraction of the tumor composed of hypoxic stem cells? Are their normal counterparts under hormonal control? Similarly, an understanding of the phar-macology of specific drugs is important. Are the tumor cells sensi-tive to the drug? Is the drug cell cycle specific? Does the drug require activation in certain normal tissue such as the liver (cyclo-phosphamide), or is it activated in the tumor tissue itself (capecit-abine)? Knowledge of specific pathway abnormalities (eg, EGFR mutations, KRAS mutations) for intracellular signaling may prove important for the next generation of anticancer drugs.

For some tumor types, knowledge of receptor expression is important. In patients with breast cancer, analysis of the tumor for expression of estrogen or progesterone receptors is important in guiding therapy with selective estrogen receptor modulators. In addition, analysis of breast cancer for expression of the HER-2/neu growth factor receptor can determine whether the human-ized monoclonal anti-HER-2/neu antibody, trastuzumab, would be appropriate therapy. In the case of prostate cancer, chemical suppression of androgen secretion with gonadotropin-releasing hormone agonists or antagonists is important. The use of specific cytotoxic and biologic agents for each of the main cancers is discussed in this section.