To doctors, nurses, pharmacists, and most other health professionals, the word chemotherapy means any drug (such as aspirin or penicillin) used for treating people with any disease. Most people, however, think of medicines to treat cancer when they hear the term chemotherapy. Two other medical terms often used to describe cancer chemotherapy are antineoplastic (meaning anticancer) therapy and cytotoxic (cell-killing) therapy.

History of Chemotherapy

The first drug used for cancer chemotherapy was not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was studied further during World War II. During a military operation in World War II, a group of people were accidentally exposed to mustard gas and were later found to have very low white blood cell counts. It was reasoned that an agent that damaged the rapidly growing white blood cells might have a similar effect on cancer. Therefore, in the 1940s, several patients with advanced lymphomas (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas. Their improvement, although temporary, was remarkable. That experience led researchers to look for other substances that might have similar effects against cancer. As a result, many other drugs have been developed to treat cancer.

Why Chemotherapy Is Different From Other Treatments

Chemotherapy is often the first choice for treating many cancers. It differs from surgery or radiation in that it is almost always used as a systemic treatment. This means the medicines travel throughout the whole body rather than being confined to one area, such as the breast, lung, or colon. This is important because chemotherapy can reach cancer cells that may have spread to other parts of the body.

More than 100 drugs are currently used for chemotherapy -- either alone or in combination with other drugs or treatments. Many more drugs are expected to become available and much promising research is being done in this field. These medicines vary widely in their chemical composition, how they are taken, their usefulness in treating specific forms of cancer, and their side effects. New medicines are first developed through research in test tubes and animals. Then their safety and effectiveness are tested in clinical trials in humans.

Chemotherapy in Clinical Trials

Clinical trials are studies of new or experimental medicines (or other new treatments). The studies are done when there is a reason to believe a new drug or a new combination of drugs may be of value in curing or controlling cancer.

If you wish to take part in a clinical trial, the researchers will fully explain to you and your family what is required. You always have the chance to refuse to take part in the study or to leave the study at a later time if you change your mind. Being in a clinical trial does not keep you from getting other medical or nursing care that you need.

People who take part in clinical trials make an important contribution to medical care because the study results will also help future patients. At the same time, they may also be among the first to benefit from these new treatments. For more information, please see the American Cancer Society document, “Clinical Trials: What You Need to Know.”

The American Cancer Society offers a clinical trials matching service for patients, their family, and friends. You can reach this service at 1-800-303-5691 or through our Web site at http://clinicaltrials.cancer.org. Based on the information you provide about your cancer type, stage, and previous treatments, this service can compile a list of clinical trials that match your medical needs. In finding a center most convenient for you, the service can also take into account where you live and whether you are willing to travel.

You can also get a list of current clinical trials by calling the National Cancer Institute's Cancer Information Service toll free at 1-800-4-CANCER or by visiting the NCI clinical trials Web site at http://www.cancer.gov/clinicaltrials.

To understand how chemotherapy works as a treatment, it is helpful to understand the normal life cycle of a cell in the body. All living tissue is composed of cells. Cells grow and reproduce to replace cells lost during injury or normal "wear and tear." The cell cycle is a series of steps that both normal cells and cancer cells go through in order to grow and reproduce to form new cells.

This discussion is somewhat technical, but it can help you understand how doctors predict which drugs are likely to work well together and how doctors decide how often doses of each drug should be given.

There are 5 phases in the cell cycle, designated by letters and numbers:

The Cell Cycle

G₀ phase (resting stage): Cells have not yet started to divide. Cells spend much of their lives in this phase. Depending on the type of cell, it can last for a few hours to a few years. When the cell is signaled to reproduce, it moves into the G1 phase.

G₁ phase: During this phase, the cell starts making more proteins to get ready to divide. This phase lasts about 18 to 30 hours.

S phase: In the S phase, the chromosomes containing the genetic code (DNA) are copied so that both of the new cells formed will have the right amount of DNA. This phase lasts about 18 to 20 hours.

G₂ phase: The G2 phase is just before the cell starts splitting into two cells. It lasts from 2 to 10 hours.

M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2 new cells.

This cell cycle is important to cancer doctors (oncologists) because many chemotherapy drugs work only on actively reproducing cells (not on cells in the resting phase, G0). Some of these drugs specifically attack cells in a particular phase of the cell cycle (the M or S phases, for example). Understanding how these drugs function helps oncologists predict which drugs are likely to work well together. Doctors can also effectively plan how often doses of each drug should be given based on the timing of the cell phases.

Although chemotherapy drugs attack reproducing cells, they cannot tell the difference between reproducing cells of normal tissues (that are replacing worn-out normal cells) and cancer cells. The damage to normal cells can result in side effects.

Each time chemotherapy is given, it involves trying to find a balance between destroying the cancer cells (in order to cure or control the disease) and sparing the normal cells (to lessen unwanted side effects).

Revised: 11/17/2006

There are 3 possible goals for chemotherapy treatment.

• Cure: If possible, chemotherapy is used to cure the cancer, meaning that the tumor or cancer disappears and does not return.

• Control: If cure is not possible, the goal is to control the disease (stop the cancer from growing and spreading) in order to extend life and provide the best quality of life. The cancer is not gone, but is controlled and managed as a chronic disease, much like hypertension or diabetes.

• Palliation: Sometimes control is unlikely if the cancer is at an advanced stage. At this point the goal is called palliation. This means that chemotherapy drugs may be used to relieve symptoms caused by the cancer, thereby improving the quality of life, even though the drugs may not lengthen life.

For some people, chemotherapy is the only treatment used in an attempt to cure, control, or palliate their cancer. In other cases, chemotherapy may be given along with other treatments. It may be used as neoadjuvant therapy (before surgery or radiation), or as adjuvant therapy (after surgery or radiation).

• Neoadjuvant chemotherapy may be used to shrink a large tumor so that it can then be removed by surgery (with a less extensive operation) or can be treated more effectively with radiation.

• Adjuvant chemotherapy is given to prevent the growth of stray cancer cells remaining in the body after surgery or radiation. In most cases, these cells cannot be seen on routine tests such as CT scans but may still be present.

Revised: 11/17/2006

Chemotherapy drugs are divided into several groups based on how they affect specific chemical substances within cancer cells, which cellular activities or processes the drug interferes with, and which specific phases of the cell cycle the drug affects. Knowing this helps oncologists decide which drugs are likely to work well together and, if more than one drug will be used, plan exactly when each of the drugs should be given (in which order and how often).

Alkylating Agents

Alkylating agents directly damage DNA to prevent the cancer cell from reproducing. As a class of drugs, these agents are not phase-specific (in other words, they work in all phases of the cell cycle). These drugs are active against chronic leukemias, non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma, and lung, breast, ovarian, and certain other cancers.

Some examples of alkylating agents include busulfan, cisplatin, carboplatin, chlorambucil, cyclophosphamide, ifosfamide, dacarbazine, mechlorethamine (nitrogen mustard), melphalan, and temozolomide.

Nitrosoureas

Nitrosoureas act in a similar way to alkylating agents. They interfere with enzymes that help copy and repair DNA. They, too, are not phase specific. Unlike many other drugs, these agents are able to travel from the blood to the brain, so they are often used to treat brain tumors. They may also be used to treat Hodgkin and non-Hodgkin lymphomas, multiple myeloma, and malignant melanoma.

Examples of nitrosoureas include streptozocin, carmustine, and lomustine.

Antimetabolites

Antimetabolites are a class of drugs that interfere with DNA and RNA growth. These agents damage cells during the S phase and are commonly used to treat leukemias, tumors of the breast, ovary, and the gastrointestinal tract, as well as other cancers.

Examples of antimetabolites include 5-fluorouracil, capecitabine, 6-mercaptopurine, methotrexate, gemcitabine, cytarabine, fludarabine, and pemetrexed.

Anthracyclines and Related Drugs

Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. These agents work in all phases of the cell cycle. Thus, they are widely used for a variety of cancers. A major consideration when giving these drugs is the toxic effects they can have on heart muscle. For this reason, life time dose limitations are often placed on these drugs.

Examples include daunorubicin, doxorubicin, epirubicin, idarubicin, and mitoxantrone.

Topoisomerase Inhibitors

These drugs interfere with enzymes called topoisomerases, which are important in accurate DNA replication. They are used to treat certain leukemias, as well as lung, ovarian, gastrointestinal, and other cancers.

Examples of topoisomerase I inhibitors include topotecan and irinotecan.

Examples of topoisomerase II inhibitors include etoposide and teniposide.

Mitotic Inhibitors

Mitotic inhibitors are plant alkaloids and other compounds derived from natural products. They can stop mitosis or inhibit enzymes from making proteins needed for reproduction of the cell. These work primarily during the M phase of the cell cycle but can cause cellular damage in all phases. They are used to treat many different types of cancer including breast, lung, myelomas, lymphomas, and leukemias. These drugs are known for their potential to cause peripheral nerve damage, which can be a dose-limiting side effect.

Examples of mitotic inhibitors include the taxanes (paclitaxel, docetaxel) and the vinca alkaloids (vinblastine, vincristine, and vinorelbine).

Corticosteroid Hormones

Steroids are natural hormones and hormone-like drugs that are useful in treating some types of cancer (lymphoma, leukemias, and multiple myeloma) as well as other illnesses. When these drugs are used to kill cancer cells or slow their growth, they are considered chemotherapy drugs. They are often combined with other types of chemotherapy drugs to increase their effectiveness.

Examples include prednisone, solumedrol, and dexamethasone.

Miscellaneous Chemotherapy Drugs

Some chemotherapy drugs act in slightly different ways and do not fit well into any of the other categories.

Examples include such drugs as L-asparaginase, hydroxyurea, dactinomycin, thalidomide, and tretinoin.

Other Types of Cancer Drug Therapies

Some other drugs and biological treatments are used to treat cancer but are not usually considered to be "chemotherapy." While chemotherapy drugs take advantage of the fact that cancer cells divide rapidly, these other drugs target different properties that set cancer cells apart from normal cells. They often have less serious side effects than those commonly caused by chemotherapy drugs because they are targeted to work primarily on cancer cells, not normal, healthy cells. Many are used in combination with chemotherapy.

Targeted therapies: As researchers have come to learn more about the inner workings of cancer cells in recent years, they have begun to create new drugs that attack cancer cells more specifically than traditional chemotherapy drugs can. Most attack cells with mutant versions of certain genes, or cells that express too many copies of a particular gene. These drugs can be used as part of primary treatment or after treatment to maintain remission or decrease recurrence.

Only a handful of these drugs are available at this time. Examples include imatinib, gefitinib, erlotinib, and bortezomib. Targeted therapies are a huge research focus and there will likely many more developed in the future.

Sex hormones: Sex hormones, or hormone-like drugs, alter the action or production of female or male hormones. They are used to slow the growth of breast, prostate, and endometrial (uterine) cancers, which normally grow in response to natural hormone levels in the body. These hormones do not work in the same ways as standard chemotherapy drugs, but rather by preventing the cancer cell from using the hormone it needs to grow, or by preventing the body from making the hormones.

Examples include anti-estrogens (tamoxifen, fulvestrant), aromatase inhibitors (anastrozole, exemestane, letrozole), progestins (megestrol acetate), anti-androgens (bicalutamide, flutamide), and LHRH agonists (leuprolide, goserelin).

Immunotherapy: Some drugs are given to people with cancer to stimulate their natural immune systems to more effectively recognize and attack cancer cells. These drugs offer a unique method of treatment, and are often considered to be separate from "chemotherapy." Compared to other forms of cancer treatment, such as surgery, radiation therapy, or chemotherapy, immunotherapy is still relatively new.

There are different types of immunotherapy. Active immunotherapies stimulate the body’s own immune system to fight the disease. Passive immunotherapies do not rely on the body to attack the disease; instead, they use immune system components (such as antibodies) created outside of the body.

Types of immunotherapies include:

• cancer vaccines (active specific immunotherapies)
• monoclonal antibody therapy (passive immunotherapies)
• non-specific immunotherapies and adjuvants (other substances or cells that boost the immune response)

For more specific information on these types of drugs see the American Cancer Society’s document, " Immunotherapy." You can get this document by calling 1-800-ACS-3456.

Revised: 11/17/2006

In some cases, the best choice of doses and schedules for giving each drug are relatively clear, and most oncologists would recommend the same treatment. In other cases, less may be known about the single best way to treat people with certain types and stages of cancer. In these situations different cancer doctors might choose different drug combinations with different schedules.

Factors to consider in choosing which drugs to use for a chemotherapy regimen include:

• type of cancer
• stage of the cancer (how far it has spread)
• age
• general state of health
• other serious health problems (such as heart, liver or kidney diseases)
• other types of anticancer treatments given in the past

Doctors take these factors into account, along with information published in medical journals and textbooks describing the outcomes of similar patients treated with chemotherapy.

Chemotherapy regimens or treatment plans may use a single drug or a combination of drugs. Oncologists usually recommend a combination of drugs for most people with cancer. This is often more effective than a single drug, as the cancer cells can be attacked in several different ways. Doctors must also consider side effects of each drug and any potential interactions among the drugs.

Side Effects

Different drugs may have different side effects, so it is often better to use moderate doses of 2 drugs that will cause bearable side effects, rather than very high doses of a single drug that might cause severe side effects and possible permanent damage to an important organ. However, there are important exceptions to this rule, and a single chemotherapy drug may be the best option for some people with certain types of cancer.

Doctors try to give chemotherapy at levels high enough to cure or control the cancer, while keeping side effects at a minimum. They also try to avoid drugs with similar and additive side effects.

Doctors try to give chemotherapy at levels high enough to cure or control the cancer, while keeping side effects at a minimum. They also try to avoid drugs with similar and additive side effects.

Drug Interactions

In addition to considering how to best combine 2 or more chemotherapy drugs, doctors must also consider potential interactions between chemotherapy drugs and other medications, including vitamins and nonprescription medicines. In some cases, these interactions may make side effects worse. In others they may interfere with the effectiveness of the chemotherapy. Therefore, it is important that you tell your doctor about all medicines, including vitamins, herbal or dietary supplements, and nonprescription medicines that you are taking.

For example, platelets are the blood cells that cause blood to clot and prevent bleeding. Many chemotherapy drugs temporarily slow down the bone marrow’s production of platelets. Taking aspirin or other related drugs can also weaken blood platelets. This is not a problem for healthy people with normal platelet counts. But for people with low platelet counts due to chemotherapy, this combination may put the patient at risk of a serious bleeding problem.

Vitamins: Many people want to take an active role in improving their general health in order to help their body's natural defenses fight the cancer and to speed up their recovery from the side effects of chemotherapy.

Because most people think of vitamins as a safe way to improve health, it is not surprising that many people with cancer take high doses of one or more vitamins. But few realize that some vitamins might make their chemotherapy less effective.

Certain vitamins, such as A, E, and C act as antioxidants. This means that they can prevent formation of ions that damage DNA. This damage is thought to have an important role in causing cancer. There is some evidence that getting enough of these vitamins (through a balanced diet and, perhaps, by taking vitamin supplements) may help reduce the risk of developing some types of cancer.

On the other hand, some chemotherapy drugs (and radiation) work by producing these same types of ions to severely damage the DNA of cancer cells, so the cells are unable to grow and reproduce. Some scientists believe that taking high doses of antioxidant vitamins during treatment may make chemotherapy or radiation less effective. Few studies have been done to thoroughly test this theory. Until we know more about the effects of vitamins on chemotherapy drugs, many oncologists recommend the following during chemotherapy:

• If your doctor has not prescribed vitamins for a specific reason, it is best not to take any on your own.

• A simple multivitamin is probably acceptable for people who want to take a vitamin supplement, but check with your doctor first.

• It is safest to avoid taking high doses of antioxidant vitamins during chemotherapy treatment. Ask your doctors when it might be safe to start such vitamins after treatment is finished.

• If you are concerned about nutrition, you can usually get plenty of vitamins by eating a well-balanced diet.

Revised: 11/17/2006

Chemotherapy treatments may be given in the following locations:

• hospital
• doctor’s office
• outpatient clinic
• home
• workplace

The type of health insurance you have, your personal preference, convenience, the type of drugs to be used, and how the drugs are to be given must all be considered when deciding the best place to give chemotherapy. For example, a chemotherapy regimen that requires placement of a special intravenous catheter and infusion over 24 hours or longer may need to be done in a hospital. The specific drugs and their doses, as well as your general state of health, will determine the expected side effects and whether you need to be monitored more closely during treatment.

Revised: 11/17/2006