GENERAL PRINCIPLES
· The management of malignancy with chemotherapy is the specific specialty of hematologist and medical oncologists. The appropriate and safe use of chemotherapy requires an understanding of various factors including, but not limited to, principles of the cell cycle and tumor growth kinetics, timing of chemotherapy administration, chemotherapy response assessment, and pharmacology of chemotherapy agents, including mechanisms of action, pharmacokinetic/pharmacodynamic properties, adverse effects, and mechanisms of drug resistance. Therefore, the prescribing and administration of these agents should only be done by those specifically trained and experienced healthcare professionals. The intent of this chapter is to provide a brief overview of some of the general principles of chemotherapy, various classes of chemotherapy agents, their respective mechanisms of action, and selected adverse effects.1,2 See Table 16-1 for chemotherapy agent classification, mechanisms of action, selected toxicities, and other pertinent information relating to these agents.
· Endocrine-related tumors are often affected by hormone therapy (e.g., antiestrogens in breast cancer, thyroid hormone to suppress thyroid cancer, and antiandrogens to inhibit prostate cancer). These agents are not discussed here, and the reader is referred to Chapters 18, 25, and 26 for more information regarding those tumors. In addition, please see Chapter 34 for a discussion of nonchemotherapeutic medications and symptomatic and supportive treatments for patients with cancer.
· Most chemotherapy agents are toxic to cells of the human body. The justification for using substances that are toxic to normal cells is that malignant cells are preferentially sensitive to the effects of chemotherapy. A balance must be struck between toxicity to malignant and harm to benign, normal tissues that are intended to be spared. This concept is described as the therapeutic index, which is the ratio of toxicity to tumor cells to that of normal cells. The therapeutic index is quite narrow for many antineoplastic agents. Traditional chemotherapeutic agents interfere with normal cell processes, typically DNA synthesis or repair. However, it should be appreciated that these agents may act in methods other than simple cell killing (e.g., as initiators of apoptosis or cellular maturation agents).
· Several newer agents have been developed that depart from the traditional concept of cell killing as their primary action. These agents are targeted to specific receptors in or on the cancer cell, often in signal transduction pathways that regulate tumor cell growth, proliferation, migration, angiogenesis, and apoptosis. Recent advances in cancer have led to the identification of several specific molecular targets for drug therapy.
Cell Cycle
· The growth and division of cells can be conceptualized by the cell cycle. There are several phases to the life cycle of the dividing cell, including the g rowth (G) phase, synthesis (S) phase, and mitosis (M) phase. There also is a “rest” phase, or G0, in which cells are not actively participating in the cell cycle. Cells can then undergo terminal differentiation or re-enter the cell cycle.
· One of the factors that influence the development of chemotherapy regimens is the phase at which the chemotherapy agent works in the cell cycle. Many chemotherapeutic agents are cell cycle specific (e.g., they have activity only in certain phases of the cell cycle). Those that are non-cell cycle specific may cause damage to a cell during any phase of the cell cycle.
REFERENCES
1. DeVita VT, Rosenberg SA, Hellman S. Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2008.
2. Pazdur R, Wagman LD, Camphausen KA, et al. Cancer Management: A Multidisciplinary Approach. 12th ed. New York: CMP Healthcare Media; 2009.