In 2012, there were 1.5 million persons with newly diagnosed invasive cancer in the United States.41 Among patients receiving chemotherapy for their disease, some will seek further care at an emergency department and require inpatient hospitalization for effects related to their treatment.10,35,38 In a prospective analysis of cancer registry data, 8.7% (179/2068) of patients receiving chemotherapy were admitted to the hospital for chemotherapy-related effects.14 Fever, neutropenia, and severe gastroenteritis are common reasons for inpatient care among patients receiving chemotherapy.14,21,35
The chemotherapeutics employed in curative and palliative regimens in many cases preclude cell division via a variety of mechanisms. Chemotherapeutics have also found expanded use in a variety of rheumatologic, dermatologic, and autoimmune disorders. Clinicians caring for patients affected by chemotherapeutics should understand the expected cellular responses from an initial and long-term exposure perspective. Chemotherapeutics cause damage primarily to deoxyribonucleic acid (DNA). This chapter will provide the reader with a focused review of cellular growth and proliferation, DNA damage from chemotherapeutics, the response of the cell to DNA damage, and the response of the tissues commonly affected by chemotherapeutics. This information will enhance the clinician’s management of patients affected by chemotherapeutics. New cancer therapies, such as targeted therapeutics and immunotherapies, are available for clinical use, and these therapies are discussed elsewhere (Chap. 50).23
CELL GROWTH AND PROLIFERATION
Cell activities are growth, metabolism, proliferation, apoptosis, and senescence. The cell cycle is the classic paradigm that depicts cell proliferation in sequential steps that are represented by phases, and it is coordinated by the cell-cycle control system (Fig. 23–1).47 The phases are G0 (resting phase), G1, S (synthesis), G2, and M (mitosis). Stem cells tend to reside at G0. When cells are stimulated by a mitotic stimulant, such as a growth factor, they leave the resting phase and enter the cell cycle. G1-, S-, and G2-phases are known as the interphase of the cell cycle, and they encompass cell growth and DNA replication. G1 and G2 are growth or gap phases, and they allow for growth and regulatory processes that aid in the transition from the S-phase to the M-phase. The G1-phase is the most variable in duration among cell types, and it controls or determines the length of the cell cycle. A typical cell cycle takes about 24 hours, and mitosis takes about 20 to 60 minutes.15 The replication of DNA occurs in the S-phase, and mitosis and cytokinesis occur in the M-phase. The G2-phase likely serves to prevent the unintended consequence of a cell undergoing separation with an incomplete copy of the DNA. The fidelity of cellular duplication is ensured by checkpoints located throughout the cell cycle.