 |
 |
 |
 |
 |
 |
COMMON QUESTIONS ABOUT BREAST CANCER: WHICH CYTOTOXIC DRUGS ARE GIVEN SYSTEMICALLY?
A variety of cytotoxic agents have been found to be effective in the systemic treatment of breast cancer. Typically, these agents are not used alone but in combination with one another or with other substances. Not all cancer cells are in the same phase of cell division at a given time; thus, some cells may be sensitive to a specific drug while other cells are resistant. To attain maximum benefit from chemotherapy it is vital to use an assortment of drugs that can act on different phases of cancer cell growth. Three categories of systemic drugs typically are used to treat breast cancer: natural products (such as anthracyclines and vinca alkaloids), alkylating agents, and antimetabolites. The categories are differentiated based on the way in which the drugs act to kill cancer cells. Drugs may be selected from each category and used separately or in combination.
Anthracyclines Doxorubicin (trade name Adriamycin), commonly used in the treatment of breast cancer, is a member of a group of antibiotics that are produced by bacteria called streptomyces. Although its exact mechanism of action is poorly understood, doxorubicin appears primarily to interfere with the copying of the primary genetic material DNA before the cell divides.
Vinca Alkaloids The vinca alkaloids include vinblastine and vincristine. These agents are derived from the periwinkle, or vinca plant, and act on cancer cells by interfering with some of the machinery involved in cell division (specifically, the mitotic spindle). The cell can then no longer replicate or copy its genetic material, and it dies in the process of division. Vinca alkaloids are also known as phase-specific agents, because they work on a particular phase of the cell growth cycle. They are most effective in cancer cells that are rapidly dividing, such as those found in newly developing tumors. Unfortunately, these drugs affect normal cells too, so that prolonged use can result in some degree of toxicity to the nervous system, or neurotoxicity.
Alkylating Agents Alkylating agents are synthetic drugs that are believed to function by interfering with a number of cellular processes: copying of the genetic material (replication), converting the cellular information into readable form (transcription), and processing the information into protein (translation). When such interference takes place, cells can no longer reproduce their genetic material—which is a requirement for continued growth. Cyclophosphamide is an example of an alkylating agent. It is commonly used in breast cancer treatment, usually in combination with other drugs such as methotrexate and 5-fluorouracil. This "CMF regimen" was developed by the National Cancer Institute and reportedly has a response rate higher than 50 percent in breast cancer patients. Cyclophosphamide is a phase-nonspecific drug, meaning that its effectiveness does not depend on the rapid division of the cells. It can therefore be used in tumors with slow growth rates (advanced tumors, for example).
Antimetabolites Methotrexate and 5-fluorouracil are both classified as antimetabolites. In general, the chemical structure of antimetabolites is similar to that of the cellular metabolites normally found within a cell. These agents can fool the cell by incorporating themselves into the cellular pathways that are involved in synthesizing materials necessary for cell growth. Both agents interfere with the making of DNA, RNA (ribonucleic acid), and proteins, an action that prevents further growth and replication of the cancer cell.
WHAT ARE THE SIDE EFFECTS OF THESE DRUGS?
Among the primary concerns of patients requiring treatment are the various side effects associated with systemic cytotoxic chemotherapy. Yet the majority of these reactions are temporary. Many side effects, such as nausea and vomiting, last only hours or days. In addition, although each drug has multiple toxicities, the patient will rarely experience all the adverse effects of any one agent. Furthermore, the development of new ways to treat nausea and vomiting, and to aid in the recovery of bone marrow, has significantly reduced the incidence and severity of the side effects of many chemotherapy drugs.
The principal cause of side effects is that the drugs involved affect not only cancer cells but normal cells—especially those characterized by rapid growth. These include cells of the hair follicles, mouth, stomach, and bone marrow. The bone marrow is composed of very fast growing cells that are busily dividing in order to make new red cells, white cells, and platelets. These blood cells eventually work their way into the bloodstream. The red cells carry oxygen to all the tissues of the body; the white cells are part of the immune system, which helps in wound healing and allows the body to fight off infection; the platelets assist in forming blood clots in damaged tissues. Chemotherapy on cells of the bone marrow can generate serious side effects, including a decrease in red cells causing anemia, a decrease in white blood cells potentially enhancing the risk of infection, and a reduction in the number of platelets thus causing bleeding or clotting problems.
The side effects of each drug have been well documented, but unfortunately they are not usually predictable. Some patients experience only mild symptoms; other women receiving the same drugs and dosages experience severe toxicities. Physical and psychological variables exert an influence as well.
*11\320\2*
Cancer