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Chemotherapy +kE-mO-!ther-u-pE

by Bruce A. Chabner, MD, Elizabeth Chabner Thompson, MD, MPH

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.

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—see Combination Cancer Therapy).

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.

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.

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

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 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).

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 it has fewer side effects.

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. Corticosteroids may increase appetite and promote weight gain. Diarrhea may be a side effect of some chemotherapy drugs. Antidiarrheal drugs can be used as needed.

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.

Some Chemotherapy Drugs

Examples

How the Drug Works

Some Side Effects

Alkylating agents

Chlorambucil

Cyclophosphamide

Melphalan

Form a chemical bond with DNA, causing breaks in DNA and errors in replication of DNA

Su00ppress bone marrow

Injure lining of stomach

Cause hair loss

May decrease fertility

Suppress the immune system

May cause leukemia

Antimetabolites

Cytarabine

Fludarabine

5-Fluorouracil

Methotrexate

6-Mercaptopurine

Block synthesis of DNA

Same as for alkylating agents

Do not increase risk of leukemia

Antimitotics

Abraxane

Cabazitaxel

Docetaxel

Paclitaxel

Vincristine

Vinorelbine

Block division of cancer cells

Same as for alkylating agents

Also can cause nerve damage

Do not cause leukemia

Topoisomerase inhibitors

Daunorubicin

Doxorubicin

Etoposide

Idarubicin

Irinotecan

Topotecan

Prevent DNA synthesis and repair through blockage of enzymes called topoisomerases

Same as for alkylating agents

Doxorubicin can cause heart damage

Platinum derivatives

Carboplatin

Cisplatin

Oxaliplatin

Form bonds with DNA, causing breaks

Same as for alkylating agents

Also can cause nerve and kidney damage and hearing loss

Hormonal therapy

Tamoxifen

Blocks estrogen action (in breast cancer)

Can cause endometrial cancer, blood clots, and hot flashes

Aromatase inhibitors

Bicalutamide

Flutamide

Leuprolide

Block androgen action (in prostate cancer)

Can cause erectile dysfunction (impotence) and diarrhea

Anastrozole

Exemestane

Letrozole

Block estrogen formation

Can cause bone loss (osteoporosis) and menopausal symptoms

Signaling inhibitors

Bosutinib

Dasatinib

Imatinib

Nilotinib

Ponatinib

Block 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 and diarrhea

Monoclonal antibodies

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

Rituximab

Induces cell death through binding to cell surface receptors on lymphocyte-derived tumors

Can cause an allergic reaction

Trastuzumab

Blocks growth factor receptors on breast cancer cells

Can cause heart failure

Biologic response modifier (drug that activates the body's immune system to fight cancer)

Interferon-alpha

Unknown

Can cause fever, chills, bone marrow suppression, thyroid deficiency, and hepatitis

Differentiating drugs (drugs that cause cancer cells to mature and stop their growth)

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

Antiangiogenic drugs (drugs that block blood vessel formation)

Bevacizumab

Blocks vascular endothelial growth factor (VEGF)

Can cause high blood pressure, protein loss in urine, bleeding, clotting, and intestinal perforation

Pazopanib

Sorafenib

Sunitinib

Vandetanib

Vemurafenib

Block VEGF receptors

Can cause high blood pressure and protein loss in urine

Tumor lysis syndrome

Tumor lysis syndrome may occur after chemotherapy because, when cancer cells are killed, they may release substances into the bloodstream. The syndrome occurs mainly in acute leukemias and non-Hodgkin lymphomas but can also occur after treatment of other types of cancer. The substances that circulate in the bloodstream may damage the kidneys or heart. 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 the substances quickly.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • TARCEVA
  • GLEEVEC
  • No US brand name
  • SPRYCEL
  • SUTENT
  • TASIGNA
  • CARAC
  • AROMASIN
  • NAVELBINE
  • CAPRELSA
  • NOLVADEX
  • CYTOXAN (LYOPHILIZED)
  • HERCEPTIN
  • CAMPTOSAR
  • PLATINOL
  • ARIMIDEX
  • ALKERAN
  • HYCAMTIN
  • ETOPOPHOS
  • OTREXUP
  • ELOXATIN
  • MARQIBO KIT
  • PURINETHOL
  • AVASTIN
  • CASODEX
  • TAXOL
  • IDAMYCIN PFS
  • LEUKERAN
  • RITUXAN
  • LUPRON
  • FEMARA
  • TAXOTERE
  • ZELBORAF
  • NEXAVAR
  • ZYLOPRIM