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69 CHAPTER 3 Chemotherapy How Chemotherapy Works Chemotherapy is the use of drugs—chemicals—that are toxic to malignant cells to treat disease. In some cases, chemotherapy is used with the intention of trying to cure cancer. When a cure is not considered possible, chemotherapy may be used to alleviate symptoms of disease and prolong life. Chemotherapy that is used simply to relieve symptoms and improve quality of life is sometimes referred to as palliative. The drugs used to treat cancer, known as antineoplastic agents, are usually taken by mouth or injected into a vein. Since this means that your whole body will be exposed to these drugs, not just the regions that contain cancer cells, chemotherapy is considered a systemic treatment. Monoclonal antibodies, another form of systemic therapy used to treat lymphoma, are discussed in Chapter 5. In the never ending battle against disease, one general principle in selecting therapeutic drugs is to exploit differences between the harmful cells, which you are trying to eliminate, and the innocent cells, which you want to protect. It’s like using an herbicide on a beautiful garden that has been invaded by weeds that are rapidly taking over and choking out all the flowers . You need to find a weed killer that is strong enough to kill (or at least control) all the poison ivy but selective enough to leave the roses and the peonies alone. The tricky part is figuring out what differences between cancer cells (the weeds in the cancer garden) and healthy cells (the flowers) might make the cancer cells susceptible to treatment. Perhaps the most striking difference between most cancer cells and most healthy cells is unrestrained growth. Therefore, most classical forms of chemotherapy —and many antineoplastic drugs used today—are designed to target rapidly dividing cells. Actively growing and dividing cells pass U 70 Treating Lymphoma through several distinct stages in what is known as the cell cycle (see Chapter 9). Some antineoplastic drugs not only act preferentially against actively dividing cells but also act at specific steps in the cell cycle. Another feature that characterizes cancer cells is their failure to undergo apoptosis—a form of programmed cell death used to eliminate cells that are no longer useful —under the appropriate circumstances. This failure to undergo apoptosis allows populations of malignant cells to accumulate. Although different antineoplastic drugs work in different ways, many of them ultimately work by triggering apoptosis, so that the damaged cells commit suicide. In the following discussion, I’ve classified drugs commonly used to treat lymphoma into five basic groups: four As and a C. The five groups are the antimetabolites, the alkylating agents, the anthracyclines, the antimitotics, and the corticosteroids. These categories are used to distinguish different types of drugs by how they work—in other words, by their mechanisms of action. Most of the drugs used to treat lymphoma fall into one of these five categories . If you’re not interested in learning how the drugs work right now, which requires reviewing some basic cell biology, feel free to skip ahead to the section on side effects. You can always come back to the section on drug mechanisms. Antimetabolites With very few exceptions, all of our cells contain DNA, a large molecule that comprises the genetic material that acts as blueprint to specify how to construct and maintain a living being. Actively dividing cells need to duplicate (or replicate) their DNA, so that each of the daughter cells will have a copy of the DNA. As discussed in more detail in Chapter 9, this process of DNA duplication takes place during the S, or synthesis, phase of the cell cycle and uses various DNA components that the cell has amassed previously. The class of antineoplastic drugs known as antimetabolites interfere with DNA synthesis. Some of these drugs inhibit the production of the compounds that make up DNA. Others mimic such compounds well enough to be mistakenly incorporated into DNA. Both of these actions inhibit DNA synthesis. Antimetabolites used in treating lymphoma include methotrexate, fludarabine , cytarabine (cytosine arabinoside), pentostatin (2′-deoxycoformycin), and cladribine (2-chlorodeoxyadenosine). Chemotherapy 71 V Alkylating Agents Another class of antineoplastic drugs, the alkylating agents, add a specific type of chemical group called an alkyl group to inappropriate sites on other molecules. The alkylating agents, which include mechlorethamine, cyclophosphamide , ifosfamide, chlorambucil, carmustine, lomustine, procarbazine , temozolomide, and dacarbazine, bind avidly to DNA and damage it. In some cases, they bind to two separate sites and form a bridge, inappropriately...


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