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Chemotherapy

By

Robert Peter Gale

, MD, PhD, Imperial College London

Last full review/revision Sep 2020| Content last modified Sep 2020
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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.

Chemotherapy is used to cure cancer. It may also decrease the chance that cancer will return, slow the growth of a cancer, or shrink tumors that are causing pain or other problems.

Although a single chemotherapy drug may be effective against some types of cancer, often doctors give several chemotherapy drugs at the same time (combination chemotherapy).

One newer 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.

The number of drugs used to treat cancer is increasing rapidly, particularly as research leads to development of immunotherapies for cancer. The National Cancer Institute maintains an up-to-date list of drugs used to treat cancer. The list provides a brief summary of each drug's uses and links to additional information.

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, surgery, or both (see also Cancer Treatment Principles).

High-dose chemotherapy

In an attempt to increase the tumor-destroying 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 chemotherapy, 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 strategies to protect the bone marrow (rescue). 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 of Chemotherapy

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. People also 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. In some states, marijuana can be prescribed to relieve nausea and vomiting caused by chemotherapy.

Low blood cell counts

Cytopenia, a deficiency of one or more types of blood cell, can develop because of the toxic effects that chemotherapy drugs have on the bone marrow (where blood cells are made). For example, a person may develop abnormally low numbers of

A person with anemia may be pale or have fatigue or weakness. People with more severe anemia may have dizziness, thirst, sweating, or even shortness of breath and chest pain. If anemia is severe, packed red blood cells can be transfused. A red blood cell growth factor, erythropoietin, also can be given, but transfusion is preferred because there is less risk of a blood clot.

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.

A person with thrombocytopenia is likely to bruise and bleed easily. If thrombocytopenia is severe, platelets can be transfused to lower the risk of bleeding.

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.

Chemotherapy may cause loss of appetite, and nutritional supplements may be needed.

Diarrhea may be a side effect of some chemotherapy drugs. Antidiarrheal drugs can be used as needed.

Depression

Depression may be the result of cancer therapy as well as the cancer itself.

Organ damage and other cancers

Sometimes chemotherapy drugs may damage other organs, such as the lungs, heart, or liver. For example, anthracyclines (such as doxorubicin), a type of topoisomerase inhibitor, 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.

Tumor lysis syndrome and cytokine release syndrome

Tumor lysis syndrome may occur after chemotherapy because, when cancer cells are killed, they may release their contents into the bloodstream. These contents may damage the kidneys or heart. Tumor lysis syndrome occurs mainly in acute leukemias and non-Hodgkin lymphomas but can also occur after treatment of other types of cancer. Sometimes doctors are able to prevent tumor lysis syndrome by giving allopurinol before and during chemotherapy. Doctors may also give fluids by vein to cause the kidneys to excrete these toxic products quickly.

Cytokine release syndrome is related to but distinct from the tumor lysis syndrome. Cytokine release syndrome occurs when large numbers of white blood cells are activated and release inflammatory substances called cytokines. It is a frequent complication of cell-based therapies such as those using CAR-T-cells and some monoclonal antibodies. Symptoms include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, rapid breathing, headache, confusion, and hallucinations. In general, treatment for mild cytokine release syndrome is supportive and involves relieving symptoms like fever, muscle pain, or fatigue. Oxygen therapy, fluids and drugs to raise blood pressure, and drugs to decrease inflammation may be needed in people with more severe cytokine release syndrome.

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