Cancer is a worldwide epidemic. Since the 1940s, great strides have been made in the development of antineoplastic agents that have extended the survival with patients afflicted with this diagnosis, and in some cases, have lead to a cure. Each individual agent has toxicity and side effects, and the choice of which agent to use in a patient will depend on the results of Phase II and III trials. This chapter will present information on the factors influencing treatment and profiles of common agents utilized in the treatment of gynecologic malignancies.
Scope of the Problem
Currently it is estimated that if every woman lives to the age of 90, 1 in 3 will develop an invasive cancer, and 1 in 5 would die from an invasive cancer . Annually, $107 billion is spent on cancer therapy, and this accounts for roughly 20 percent of all health care costs .
Cell Cycle and Growth Kinetics
The growth capacity of both normal and cancerous cells can be regulated and influenced by internal and external factors. Differences in the growth of various tissues contribute to chemotherapy strategies. In addition, these differences allow us to better understand toxicities associated with various chemotherapy agents.
All tissues can be divided broadly into three distinct growth patterns: static, expanding, and renewing. Static populations are well-differentiated tissues that, after initial proliferative activity, rarely undergo cell division. Examples of static cells included neurons and striated muscle tissue. Expanding populations of cells are ones that under special circumstances will proliferate. These cells are normally quiescent (liver, kidney), but when tissue injury occurs, they go through a surge of proliferation. Renewing cells are constantly in a proliferative state. They have a high cellular turnover, are constantly undergoing cell division, and have a high rate of cell loss. This occurs in bone marrow, gastrointestinal mucosa, and epidermal tissue. Chemotherapy toxicities are generally seen in renewing cell populations, with static and expanding cells having less injury with these agents.
Tumor cells demonstrate unregulated cellular growth, and as such have lost many of the cellular mechanisms operative in noncancerous tissues. These include normal cell cycle regulation and loss of apoptosis. The loss of these brake points leads to continued cell proliferation, and eventually to the death of the host.