Chemotherapy involves the use of drugs to destroy cancer cells. Although an ideal drug would destroy cancer cells without harming normal cells, most drugs are not that selective. Instead, drugs are designed to inflict greater damage on cancer cells than on normal cells, typically by using drugs that affect a cell's ability to grow. Uncontrolled and rapid growth is characteristic of cancer cells. However, because normal cells also need to grow, and some grow quite rapidly (such as those in the bone marrow and those lining the mouth and intestine), all chemotherapy drugs affect normal cells and cause side effects.

One new approach to limiting side effects and increasing effectiveness uses a variety of "molecularly targeted" drugs. These drugs kill cancer cells by attacking specific pathways and processes vital to the cancer cells' survival and growth. For example, cancer cells need blood vessels to provide nutrients and oxygen. Some drugs can block blood vessel formation to cancer cells or the master signaling pathways that control cell growth. Imatinib, the first such drug, is highly effective in chronic myelocytic leukemia and certain cancers of the digestive tract. Erlotinib and gefitinib target receptors located on the surface of cells in non–small cell lung cancer. Molecularly targeted drugs have proven useful in treating many other cancers, including breast and kidney cancers.

Not all cancers respond to chemotherapy. The type of cancer determines which drugs are used, in what combination, and at what dose. Chemotherapy may be used as the sole treatment or combined with radiation therapy or surgery, or both.

High-Dose Chemotherapy: In an attempt to increase the antitumor effects of cancer drugs, the dose may be increased and the time between cycles of therapy may be decreased (dose-dense chemotherapy). Dose-dense chemotherapy, with shortened rest periods, is routinely used in breast cancer treatment. High-dose chemotherapy is often used for treatment of people whose cancer has recurred after standard dose therapy, particularly for people with myeloma, lymphoma, and leukemia. However, high-dose chemotherapy can cause life-threatening injury to the bone marrow. Therefore, high-dose chemotherapy is commonly combined with bone marrow rescue strategies. In bone marrow rescue, bone marrow cells are harvested before the chemotherapy and returned to the person after chemotherapy. In some cases, stem cells can be isolated from the bloodstream rather than from the bone marrow and can be infused back into the person after chemotherapy to restore bone marrow function.

Side Effects

Chemotherapy commonly causes nausea, vomiting, loss of appetite, weight loss, fatigue, and low blood cell counts that lead to anemia and increased risk of infections. With chemotherapy, people often lose their hair, but other side effects vary according to the type of drug.

Nausea and Vomiting: These symptoms can usually be prevented or relieved with drugs (antiemetics). Nausea may also be reduced by eating small meals and by avoiding foods that are high in fiber, that produce gas, or that are very hot or very cold.

Low Blood Cell Counts: Cytopenia, a deficiency of one or more types of blood cell, can develop because of the toxic effects chemotherapy drugs have on bone marrow (where blood cells are made). For example, a person may develop abnormally low numbers of red blood cells (anemia), white blood cells (neutropenia or leukopenia), or platelets (thrombocytopenia). If anemia is severe, specific growth factors, such as erythropoietin or darbepoietin, can be given to increase red blood cell formation, or packed red blood cells can be transfused. If thrombocytopenia is severe, platelets can be transfused to lower the risk of bleeding.

A person with neutropenia is at increased risk of developing an infection. A fever higher than 100.4° F in a person with neutropenia is treated as an emergency. Such a person must be evaluated for infection and may require antibiotics and even hospitalization. White blood cells are rarely transfused because, when transfused, they survive only a few hours and produce many side effects. Instead, certain substances (such as granulocyte-colony stimulating factor) can be administered to stimulate white blood cell production.

Other Common Side Effects: Many people develop inflammation or even sores of the mucous membranes, such as the lining of the mouth. Mouth sores are painful and can make eating difficult. Various oral solutions (usually containing an antacid, an antihistamine, and a local anesthetic) can reduce the discomfort. On rare occasions, people need nutritional support by a feeding tube that is placed directly into the stomach or small intestine or even by vein. A variety of drugs can reduce the diarrhea caused by radiation therapy to the abdomen

Organ Damage and Other Cancers: Sometimes drugs may damage other organs, such as the lungs, heart, or liver. For example, anthracyclines cause heart damage when used in high total doses

People treated with chemotherapy, particularly alkylating agents, may have an increased risk of developing leukemia several years after treatment. Some drugs, especially alkylating agents, cause infertility in some women and in most men who receive these treatments

Chemotherapy Drugs Examples How the Drug Works Side Effects Alkylating agents Cyclophosphamide Chlorambucil Melphalan Form chemical bond with DNA, causing breaks in DNA and errors in replication of DNA Suppress bone marrow Injure lining of stomach Cause hair loss May decrease fertility Suppress the immune system May cause leukemia Antimetabolites Methotrexate Cytarabine Fludarabine 6-Mercaptopurine 5-Fluorouracil Block synthesis of DNA Same as for alkylating agents Do not increase risk of leukemia Antimitotics Vincristine Paclitaxel Vinorelbine Docetal Abraxane Block division of cancer cells Same as for alkylating agents Also can cause nerve damage Do not cause leukemia Topoisomerase inhibitors Doxorubicin Irinotecan Prevent DNA synthesis and repair through blockage of enzymes called topoisomerases Same as for alkylating agents Doxorubicin can cause heart damage Platinum derivatives Cisplatin Carboplatin Oxaliplatin Form bonds with DNA causing breaks Same as for alkylating agents Also can cause nerve and kidney damage, hearing loss Hormonal therapies Tamoxifen Blocks estrogen action (in breast cancer) Can cause endometrial cancer, blood clots, hot flashes Aromatase inhibitors Bicalutamide Blocks androgen action (in prostate cancer) Can cause erectile dysfunction (impotence) and diarrhea Anastrozole Examestane Letrozole Block estrogen formation Can cause bone loss (osteoporosis) and menopausal symptoms Signaling inhibitors Imatinib Blocks signal for cell division in chronic myelocytic leukemia Can cause abnormal liver function test results and fluid retention Gefitinib Erlotinib Blocks epidermal growth factor receptor Can cause rash, diarrhea Monoclonal antibodies Rituximab Induces cell death through binding to cell surface receptor on lymphocyte-derived tumors Can cause allergic reaction Trastuzumab Blocks growth factor receptor on breast cancer cells Can cause heart failure Gemtuzumab ozogamicin Contains a specific antibody that attaches to a receptor found on leukemic cells and then delivers a toxic dose of its chemotherapeutic component to the leukemic cells Can cause prolonged platelet suppression, which increases the risk of bleeding Biologic response modifiers Interferon-alpha Unknown Can cause fever, chills, bone marrow suppression, thyroid deficiency, hepatitis Differentiating agents Tretinoin Induces differentiation and death of leukemic cells Can cause severe difficulty with breathing (respiratory distress) Arsenic trioxide Induces differentiation and death of leukemic cells Causes abnormal heart rhythms and a rash Agents that block blood vessel formation (antiangiogenic agents) Bevicizumab Blocks vascular endothelial growth factor (VEGF) Can cause high blood pressure, protein loss in urine, bleeding, clotting, intestinal perforation Serafinib Sunitinib Block VEGF receptor Can cause high blood pressure and protein loss in urine

Last full review/revision August 2007 by Bruce A. Chabner, MD; Elizabeth Chabner Thompson, MD, MPH