Chemotherapy

Definition

Chemotherapy is the systemic (whole body) treatment of cancer with anticancer drugs.

Purpose

The main purpose of chemotherapy is to kill cancer cells. It can be used as the primary form of treatment or as a supplement to other treatments. Chemotherapy is often used to treat patients with cancer that has spread from the place in the body where it started (metastasized), but it may also be used the keep cancer from coming back (adjuvant therapy). Chemotherapy destroys cancer cells anywhere in the body. It even kills cells that have broken off from the main tumor and traveled through the blood or lymph systems to other parts of the body.

Chemotherapy can cure some types of cancer. In some cases, it is used to slow the growth of cancer cells or to keep the cancer from spreading to other parts of the body. When a cancer has been removed by surgery, chemotherapy may be used to keep the cancer from coming back (adjuvant therapy). It is also helpful in reducing the tumor size prior to surgery (primary [neoadjuvant] chemotherapy). Chemotherapy can ease the symptoms of cancer (palliate), helping some patients have a better quality of life.

Types of chemotherapy

Chemotherapy may be used as the first line of treatment or it may be started after a tumor is removed. A variety of factors, including the type and stage of cancer, will determine the type of chemotherapy used.

Adjuvant chemotherapy

Adjuvant chemotherapy refers to giving patients anti-cancer drugs after the primary tumor has been removed and there is no evidence that cancer remains in the body. It was first studied in the 1950s. This form of treatment initially gained popularity because it showed promise in improving the survival for patients with certain cancers. The theory was that adjuvant chemotherapy would attack microscopic cancer cells that remained after tumor removal. Adjuvant chemotherapy may be effective in some types of cancers, including breast cancer , colorectal cancer, osteogenic sarcoma, and Wilms' tumor .

A patient's response to adjuvant therapy is determined by a variety of factors, including drug dosage, schedule of drug therapy, and drug resistance . Toxic side effects and cost-effectiveness are other important issues. This area is undergoing further investigation.

Primary (neoadjuvant) chemotherapy

Primary chemotherapy, also sometimes called neoadjuvant chemotherapy or induction chemotherapy, is the use of anticancer drugs as the main form of treatment. Chemotherapy can be the primary treatment with cancers such as these: certain lymphomas, childhood and some adult forms of Hodgkin's disease , Wilms' tumor, embryonal rhabdomyosarcoma , and small cell lung cancer.

Primary chemotherapy can also be used to treat tumors prior to surgery or radiation. In some cases, the tumor may be so large that surgery to remove it would destroy major organs or would be quite disfiguring. Primary neoadjuvant chemotherapy may reduce the tumor size, making it possible for a surgeon to perform a less traumatic operation. Examples of cancers in which primary chemotherapy may be followed-up with less extensive surgeries include: anal cancer , bladder cancer , breast cancer, esophageal cancer , laryngeal cancer , osteogenic sarcoma, and soft tissue sarcoma.

An advantage of primary chemotherapy is that the blood vessels are intact since they have not been exposed to surgery or radiation. Therefore, drugs can easily travel through the bloodstream toward the tumor. In fact, the therapy can improve the tumor's blood flow, making it more receptive to the impact of radiation. In addition, the use of chemotherapy before surgical removal of cancer allows the physician to assess the responsiveness of the tumor to the drug (s) used. Since not all chemotherapy regimens are equally effective, knowing how a particular tumor responds to the chemotherapy regimen prescribed can be an advantage in treating the disease.

Primary chemotherapy does have drawbacks. Some cancer cells may be drug-resistant, making the therapy ineffective. (Although discovering that the drug is ineffective minimizes the number of cycles of the drug that the patient must undergo.) The drug may not significantly reduce tumor size, or the tumor may continue to grow despite treatment. Furthermore, the initial use of a drug may lead to higher toxicity when chemotherapy is given later in the course of treatment.

Primary chemotherapy is becoming the norm in treating some patients with certain cancers, such as specific types of lymphomas, some small cell lung cancers, childhood cancers , head and neck cancers , and locally advanced breast cancer. Additional research using this type of chemotherapy is underway.

Combination chemotherapy

In most cases, single anticancer drugs cannot cure cancer alone. The use of two or more drugs together is often a more effective alternative. This approach is called combination chemotherapy. Scientific studies of different drug combinations help doctors learn which combinations work best for various types of cancers.

Combination chemotherapy provides a higher chance of destroying cancerous cells. An oncologist decides which chemotherapy drug or combination of drugs will work best for each patient. Different drugs attack cancer cells at varying stages of their growth cycles, making the combination a stronger weapon against cancerous cells. Furthermore, using a combination of drugs may reduce the chance of drug resistance.

When selecting the combination of drugs, a variety of factors are examined. It is important for each drug to be effective against the particular tumor being targeted. Toxicity must also be studied to be sure that each different drug used in a combination is not toxic for the same organ. For example, if two drugs are each toxic to the liver, the combination could be more damaging to that organ.

How chemotherapy is given

Chemotherapy medications enter a person's body in different ways, depending on the drugs to be given and the type of cancer.

The goal is for the chemotherapy drug to reach the tumor. Some areas of the body are less accessible for anticancer drugs, and this is considered when the doctor determines the route of administration. For example, the blood-brain barrier refers to the inability of some anticancer drugs to travel through the bloodstream and enter the brain or the fluid surround the brain. Areas of the body that are inaccessible to a particular drug create a phenomenon called the sanctuary effect. In other words, the tumor is safe because the chemotherapy cannot reach it. To overcome a problem such as this one, the doctor must consider the route that will most effectively deliver the drug to the cancerous cells. Chemotherapy may be given by one or more of the following methods:

• oral (by mouth)
• injection (intramuscular or subcutaneous)
• intravenous (IV)
• intra-arterial (into the arteries)
• intralesional (directly into the tumor)
• intraperitoneal (into the peritoneal cavity)
• intrathecal (into the spinal fluid)
• topically (applied to the skin)

Orally

Oral chemotherapy is given by mouth in the form a pill, capsule, or liquid. This is the easiest method and can usually be done at home.

Injection

Intramuscular (IM) chemotherapy is injected into a muscle. Chemotherapy given by intramuscular injection is absorbed into the blood more slowly than IV chemotherapy. Because of this, the effects of IM chemotherapy may last longer than chemotherapy given intravenously. Chemotherapy may also be injected subcutaneously (SQ or SC), which means under the skin.

Intravenous

Intravenous (IV) chemotherapy is the most common way to deliver anticancer drugs into a person's body. The drug is injected directly into a vein. A small needle is inserted into a vein on the hand or lower arm.

Chemotherapy may also be given by a catheter or port inserted into a central vein or body cavity, where it can remain for an extended period of time. A port is a small reservoir or container that is placed in a vein or under the skin in the area where the drug will be given. These methods eliminate the need for repeated injections and may allow patients to spend less time in the hospital while receiving chemotherapy. A common location for a permanent catheter is the external jugular vein in the neck. Catheters and ports require meticulous care and cleaning to avoid complications, such as blood clots or infection. They may be inserted using a surgical procedure.

Chemotherapy given by the IV method may be administered intermittently or continuously. The main reasons for a continuous flow are to increase effectiveness against the tumor or to lower toxicity. Some drugs perform more effectively when exposed to the cancer over a period of time, making a continuous flow more desirable. A drug that is commonly used to treat colorectal cancer in continuous infusions is fluorouracil , also known as 5-FU. A drug that has less toxicity to the heart with continued infusion is doxorubicin , also known as Adriamycin. In some cases, toxicity occurs when the drug reaches a peak level. Offering a continuous infusion prevents the drug from reaching this level, thus lowering the chance of toxic side effects.

Intra-arterial

Cancerous tumors require a supply of blood and oxygen so that they can grow. They get these essentials from the arteries that supply organs with their blood and oxygen. Putting chemotherapy drugs into the arteries provides good access to the cancerous tumor. Intra-arterial chemotherapy is not designed for all patients. The tumor must be confined to one specific organ and the blood supply to the tumor must be accessible. The liver is

the most common organ targeted in this type of chemotherapy, although it is also effective in certain brain cancers. Its use in head and neck cancers remains controversial. Further use of this type of chemotherapy is being investigated.

A catheter is inserted using radiologic techniques or surgery. Surgical insertion is the most common. Although it is less costly and less stressful, radiologic insertion results in a catheter that cannot stay in place as long as one inserted surgically. A radiologically inserted catheter stays in place for weeks compared to surgically inserted catheters designed to stay in place from weeks to years. In the long run, the surgically implanted arterial catheter has fewer complications, such as thrombosis or infection, and is more highly acceptable to the patient.

The radiologically placed catheter is initially inserted into an artery in the person's arm or leg, and then it is guided to its final destination near the tumor, where it can remain for an extended period.

The catheters require meticulous care to keep them clean and securely in place, which lessen the chance of complications. Problems associated with catheters include movement of the tip, blood clots and infection.

Pumps may be used to move the drug through the artery and into the tumor. A pump may be external or internally planted. External pumps range from large machines found in hospitals to portable wallet-sized devices. Implanted pumps give patients greater freedom, and are safe and effective. Some internal pumps deliver a constant flow of drugs, while others are programmed to deliver intermittent doses.

Drugs used for intra-arterial chemotherapy include FUDR (floxuridine ), FU (fluorouracil), mitomycin, cisplatin , and streptomycin. Less frequently, doxorubicin has been used intra-arterially for treating certain cancers of the breast, bladder, stomach, and other areas.

Intralesional

Intralesional chemotherapy is the injection of anti-cancer drugs directly into a tumor that is in the skin, under the skin, or in an organ inside the body. Some examples involving the use of intralesional chemotherapy include melanoma and Kaposi's sarcoma . This type of chemotherapy shows promise for other malignancies such as laryngeal cancers, and further uses are under investigation.

Intraperitoneal

Intraperitoneal (IP) chemotherapy is administered into the abdominal cavity through a catheter or port that is put into place by surgery.

Ovarian cancer is sometimes treated with IP chemotherapy because this type of cancer usually stays within a confined area. This type of therapy is only suitable for some patients. Ovarian cancer patients whose tumors have a diameter greater than two centimeters may not receive this therapy because the anticancer drug does not reach very far into the tumor. Also, patients whose cancers are resistant to certain drugs may not undergo IP therapy. Patients with smaller tumors, or those who show response to chemotherapy are better candidates.

Drugs used in IP chemotherapy include cisplatin, paclitaxel , floxuridine, 5-FU, mitoxantrone , carboplatin , and alfa-interferon.

Intrathecal

Intrathecal chemotherapy is the injection of anti-cancer drugs into the spinal fluid. This method is used primarily in treating acute lymphocytic leukemia . It is effective in placing the anticancer drug directly into the cerebrospinal fluid that surrounds the spinal cord and the brain. A spinal tap, also called lumbar puncture , is the procedure usually used to gain access to the spinal fluid. If many treatments are needed, a device called an Ommaya reservoir may be used. This device is inserted under the scalp and allows injection of anticancer drugs throughout the spinal fluid via the reservoir. Patients can go home with the Ommaya reservoir in place. Common drugs used intrathecally include methotrexate and cytarabine , which are usually given by a doctor with a nurse's assistance. Some leukemia patients receive IV treatments at the same time they are having intrathecal treatments.

Topical chemotherapy

Topical chemotherapy is given as a cream or ointment applied directly to the cancer. This method is more common in the treatment of certain types of skin cancer. An example is fluorouracil, also known as 5-FU, which is a topical anticancer cream.

Chemotherapy drugs

More than 50 chemotherapy drugs are currently available to treat cancer and many more are being tested for their ability to destroy cancer cells. About 30% of anticancer drugs come from or are derived from natural sources. Most chemotherapy drugs interfere with the cell's ability to grow or multiply. Although these drugs affect all cells in the body, many useful treatments are most effective against rapidly growing cells. Cancer cells grow more quickly than most other body cells. Other cells that grow fast are cells of the bone marrow that produce blood cells, cells in the stomach and intestines, and cells of the hair follicles. Therefore, the most common side effects of chemotherapy are linked to their effects on other fast growing cells. Some tumor cells are resistant to drugs, making them more difficult to target.

Alkylating agents

Alkylating drugs kill cancer cells by directly attacking DNA, the genetic material of the genes. By attacking the DNA, the drug prevents the cell from forming new cells. Nitrogen mustards, which were the first nonhormonal chemicals with anticancer abilities, are alkylating drugs. Cyclophosphamide and Mustargen are two alkylating agents. Cyclophosphamide, the most common alkylating agent, is often used in combination with other drugs to treat breast cancer, lymphomas, and other tumors in both children and adults. Mustargen is part of the treatment for Hodgkin's disease.

Platinum drugs

Drugs containing platinum are useful in treating a number of malignant tumors. Examples of these drugs include cisplatin, carboplatin, and oxaliplatin . Cisplatin is more toxic than the other two, and it is subject to resistance by the cancerous tumors. In fact, it was cisplatin's high toxicity that prompted the discovery of the other two platinum drugs, which are less toxic and more effective. Carboplatin has been shown to cause less nausea and vomiting than cisplatin, and it has replaced cisplatin in many treatment regimes. New platinum drugs are being investigated.

Antimetabolites

Antimetabolites interfere with the production of DNA and keep cells from growing and multiplying. They are used to treat a variety of cancers including breast cancer, leukemia, lymphoma , colorectal cancer, head and neck cancer, osteogenic sarcoma, choriocarcinoma (a rare uterine cancer), and urothelial cancer. Some drug resistance has occurred with these types of drugs. Examples of antimetabolites are 5-fluorouracil (5-FU), Tegafur, and Uracil.

Antitumor antibiotics

Antitumor antibiotics are made from natural substances such as fungi in the soil. They interfere with important cell functions, including production of DNA and cell proteins. Doxorubicin, daunorubicin , idarubicin , epirubicin , dactinomycin , and bleomycin belong to this group of chemotherapy drugs.

Topoisomerase inhibitors

Topoisomerase inhibitors are effective in treating a number of cancers. Topoisomerase is an enzyme necessary for the replication of DNA within the cell. The topoisomerase inhibitors act on this enzyme, and the cell eventually dies. Drugs in this class include etoposide and teniposide .

Camptothecin analogues are also classed as topoisomerase inhibitors. Specific drugs are topotecan and irinotecan .

Anthracyclines are topoisomerase inhibitors such as daunorubicin, doxorubicin, epirubicin, and idarubicin. A drawback of the anthracyclines is their toxicity to the heart. Because of this, there have been efforts to develop synthetic drugs similar to the anthracyclines. Mitoxantrone and losoxantrone are two examples of synthetics.

Dactinomycin is another drug acting on the DNA of the cell. It is an effective drug for treating a variety of cancers including Ewing's sarcoma , Wilms' tumor, embryonal rhabdomyosarcoma, and gestational choriocarcinoma (rare uterine cancer). It has also been used to treat cancer of the testicles, lymphoma, and Kaposi's sarcoma.

Antimicrotubule Agents

A microtubule is an important part of a cell, and is the target of a class of anticancer drugs.

Vinca alkaloids, which attack the cell's micro-tubules, are found in very small amounts in the periwinkle plant. Three types of vinca alkaloids are vincristine , vinblastine and vinorelbine . Vincristine is used more frequently in treating childhood, rather than adult, cancers. It is used in combination chemotherapy for the treatment of acute lymphocytic leukemia and Hodgkin's and non-Hodgkin's lymphoma, as well as other cancers. Vinblastine is used in combination chemotherapy for Kaposi's sarcoma, as well as cancers of the bladder, brain and breast. It is also used in the treatment of advanced cases of lymphoma and germ cell cancers.

The taxanes are another group of antimicrotubule agents. They are from the Pacific yew tree, and were first isolated in 1963. In 1971, paclitaxel was found to be an active ingredient in the bark of this tree. Paclitaxel has shown promising results in people with cancers of the ovaries or breasts. It is also used for AIDS patients who have Kaposi's sarcoma, and in combination with cisplatin in the treatment of non-small cell lung cancer. Paclitaxel is also part of the chemotherapy treatment in breast cancer patients whose cancer has spread to the lymph nodes. A related drug, docetaxel is used for treating advanced cases of breast cancer as well as certain non-small cell lung cancers.

Estramustine phosphate is related to nitrogen mustard. This drug acts on the microtubule of the cell, and has been effective in treating certain prostate cancers.

Hormones

Steroid hormones slow the growth of some cancers that depend on hormones. For example, tamoxifen is used to treat breast cancers that depend on the hormone estrogen for growth. Additionally, androgen suppression therapy is used in the treatment of prostate cancer . The goal of this therapy is to lower the levels of male hormones (androgens), especially testosterone , that can cause prostate cancer cells to grow. Lutenizing hormone-releasing hormone (LHRH) analogs lower testosterone levels by decreasing the androgens produced by the testicles. Two LHRH analogs available in the U.S. in 2001 are leuprolide acetate and goserelin .

Treatment location and schedule

Patients may take chemotherapy at home, in the doctor's office, or as an inpatient or outpatient at the hospital. Most patients stay in the hospital when first beginning chemotherapy, so their doctor can check for any side effects and change the dose if needed. A very important part of chemotherapy is determining the appropriate dose. To do this, the doctor must consider the person's size as well as any toxic side effects the drug may have.

How often and how long chemotherapy is given depends on the type of cancer, how patients respond to the drugs, patients' health and ability to tolerate the drugs, and on the types of drugs given. Chemotherapy administration may take only a few minutes or may last as long as several hours. Chemotherapy may be given daily, weekly, or monthly. A rest period may follow a course of treatment before the next course begins. In combination chemotherapy, more than one drug may be given at a time, or they may be given alternately, one following the other.

Precautions

There are many different types of chemotherapy drugs. Oncologists, doctors who specialize in treating cancer, determine which drugs are best suited for each patient. This decision is based on the type of cancer, the patient's age and health, and other drugs the patient is taking. Some patients should not be treated with certain chemotherapy drugs. Age and other conditions may affect the drugs with which a person may be treated. Heart disease, kidney disease, and diabetes are conditions that may limit the choice of treatment drugs. Pregnancy is another precaution because of the anticancer drug's impact on fetal development.

Preparation

A number of medical tests are done before chemotherapy is started. The oncologist will determine how much the cancer has spread from the results of x rays and other imaging tests and from samples of the tumor taken during surgery.

A patient's complete medical history will be taken, including any past chemotherapy. The patient will be asked to sign a consent form, and will be told about the drugs and procedures involved with chemotherapy. It is essential that the patient understand both the risks and benefits of treatment.

The nurse explains what will take place during the treatment, and what side effects to expect. In addition to the physical side effects, the stress of chemotherapy will be discussed. Patients who are better prepared tend to have fewer side effects and a higher emotional ability to handle the chemotherapy treatments.

Blood tests give the doctor important information about the function of the blood cells and levels of chemicals in the blood. A complete blood count (CBC) is commonly done before and regularly during treatment. The CBC shows the numbers of white blood cells, red blood cells, and platelets in the blood. Because chemotherapy affects the bone marrow, where blood cells are made, levels of these cells often drop during chemotherapy. The white blood cells and platelets are most likely to be affected by chemotherapy. A drop in the white blood cell count means that the immune system cannot function properly. Low levels of platelets can cause a patient to bleed easily from a cut or other wound. A low red blood cell count can lead to anemia (deficiency of red blood cells) and fatigue .

When a chemotherapy treatment takes a long time, the patient may prepare for it by wearing comfortable clothes. Bringing a book to read or a tape to listen to may help pass the time and ease the stress of receiving chemotherapy. Some patients bring a friend or family member to provide company and support during treatment.

Sometimes, patients taking chemotherapy drugs known to cause nausea are given medications called anti-emetics before chemotherapy is administered. Anti-emetic drugs help to lessen feelings of nausea. Two anti-nausea medications that may be used are Kytril and Zofran.

Other ways to prepare for chemotherapy and help lessen nausea are:

• Regularly eat nutritious foods and drink lots of fluids.
• Eat and drink normally until about two hours before chemotherapy.
• Eat high carbohydrate, low-fat foods and avoid spicy foods.

Aftercare

To control side effects after chemotherapy, patients should:

• Follow any instructions given by the doctor or nurse.
• Take all prescribed medications.
• Eat small amounts of bland foods.
• Drink lots of fluids.
• Get plenty of rest.

Some patients find it helps to breathe fresh air or get mild exercise, such as taking a walk.

Risks

Chemotherapy drugs are toxic to normal cells as well as cancer cells. A dose that will destroy cancer cells will probably cause damage to some normal cells. Doctors adjust doses to do the least amount of harm possible to normal cells. Some patients feel few or no side effects, and others may have more serious side effects. In some cases, a dose adjustment is all that is needed to reduce or stop a side effect.

A person may experience a side effect right away or the reaction may be delayed. Side effects are classified as follows:

• acute, develops within 24 hours of treatment
• delayed, develops after 24 hours but within six to eight weeks of treatment
• short-term, combination of acute and delayed
• late/long-term, develops months or years after treatment, or lasts for an extended period of time
• expected, a side effect that develops in three quarters of patients
• common, occurs in 25-75% of patients
• uncommon/occasional, occurs in less than a quarter of patients
• rare, occurs in 5% of patients
• very rare, occurs in less than 1% of patients

Certain chemotherapy drugs have more side effects than others. While some drugs have immediate effects, other effects are delayed. Patients are encouraged to discuss the potential for side effects with their doctor. They must seek immediate medical attention if they are experiencing any unusual symptoms. Some of the most common side effects are discussed in this section.

Nausea and vomiting/loss of appetite

Nausea and vomiting are common, but can usually be controlled by taking antinausea drugs, drinking enough fluids, and avoiding spicy foods. Loss of appetite (anorexia ) may be due to nausea or the stress of undergoing cancer treatment. Drugs that have a high likelihood of causing nausea or vomiting include cisplatin, mechlorethamine , streptozocin , dacarbazine , carmustine , and dactinomycin. Those with moderate nausea-inducing potential include cyclophosphamide, doxorubicin, carboplatin, mitomycin, and L-asparaginase . Anticancer drugs with a low chance of causing nausea or vomiting include fluorouracil, methotrexate, etoposide, vincristine, and bleomycin.

Hair loss

Some chemotherapy drugs cause hair loss (alopecia ), but it is almost always temporary. Hair re-growth may not begin until several weeks have passed since the final treatment. This is the most common impact that chemotherapy has on the outer surfaces of the body. In some patients, an ice wrap, called an ice turban, can reduce hair loss. The effectiveness will depend on factors such as the type of drug, dose, and treatment schedule. This preventive treatment must be avoided by patients with leukemia, lymphoma, mycosis fungoides or by those with scalp tumors. People should use with caution if they have conditions such as vasculitis, cryoglobulinemia or a history of radiation to the head. Patients should discuss the ice turban treatment with their doctor before trying it.

Anemia and fatigue

Low blood cell counts caused by the effect of chemotherapy on the bone marrow can lead to anemia , infections, and easy bleeding and bruising. Patients with anemia have too few red blood cells to deliver oxygen and nutrients to the body's tissues. Anemic patients feel tired and weak. If red blood cell levels fall too low, a blood transfusion may be given.

Infections

Patients receiving chemotherapy are more likely to get infections. This happens because their infection-fighting white blood cells are reduced. The level of reduction can vary depending on the dose and schedule of treatments, and whether the drug is used alone or in combination with other anticancer agents.

It is important for chemotherapy patients to avoid infection. When the white blood cell count drops too low, the doctor may prescribe medications called colony stimulating factors that help white blood cells grow. Neupogen and Leukine are two colony stimulants used as treatments to help fight infection.

Easy bleeding and bruising

Platelets are blood cells that make the blood clot. When patients do not have enough platelets, they may bleed or bruise easily, even from small injuries. Patients with low blood platelets should take precautions to avoid injuries. Medicines such as aspirin and other pain relievers can affect platelets and slow down the clotting process.

Sores in the mouth

Chemotherapy can cause irritation and dryness in the mouth and throat. An inflammation in the mouth is called stomatitis . Painful sores may form that can bleed and become infected. Precautions to avoid this side effect include getting dental care before chemotherapy begins, brushing the teeth and gums regularly with a soft brush, and avoiding mouth washes that contain salt or alcohol. Good oral hygiene is important. It is helpful for some patients to chew on ice chips for half an hour during chemotherapy treatments, but this should be discussed with the doctor before it is done.

Neuropathy and other damage to the nervous system

Cancer patients may develop neurological problems due to the cancer or the anticancer drugs. A variety of problems can develop, including altered mental alertness, changes in taste and smell, seizures, and peripheral neuropathy (tingling and burning sensations and/or weakness or numbness in the hands and/or feet). Different drugs can lead to different types of neurological disorders. Patients should discuss neurological symptoms with the doctor.

Heart damage

Some anticancer drugs are damaging to the heart. In these cases, the dosage is closely monitored in an attempt to avoid heart damage. Specific drugs that may be toxic to the heart include doxorubicin, daunorubicin, high doses of cyclophosphamide, and, in some cases, 5-FU. Patients experiencing chest pain or any cardiac symptoms should seek immediate medical help.

Kidney damage

A number of anticancer drugs can damage the kidney. Examples include high doses of methotrexate or 6-MP, as well as regular doses of L-asparaginase, cisplatin, mithramycin, streptozocin, and mitomycin C. Some kidney problems can be lessened by taking in adequate amounts of fluids. A secondary danger of kidney damage is that a less functional kidney can be more susceptible to further toxicity caused by other anticancer drugs that the patient is taking.

Respiratory problems

Cancer patients who have had radiation in the chest area are more susceptible to respiratory complications. Nitrosourea or bleomycin cause the most common type of respiratory toxicity, called pulmonary fibrosis. Patients should get immediate medical assistance if they have difficulty breathing.

Sexual function

Some drugs can lead to impaired sexual function. Alkylating agents and procarbazine may result in the absence of sperm in a man and the lack of menstruation in a woman. Patients of child-bearing age are usually told to refrain from conceiving while undergoing chemotherapy because of the defects it can cause in the fetus.

Vision problems

Some anticancer drugs can impact a person's vision. High doses of cyclophosphamide can cause blurred vision in children, while some alkylating agents can cause cataracts. Tamoxifen may be damaging to the retina, and cisplatin can damage the optic nerve. Conjunctivitis, commonly called pinkeye, is a treatable problem that occurs with many anticancer drugs.

Results

The main goal of chemotherapy is to cure cancer. Many cancers are cured by chemotherapy. The chemo-therapy treatment may be used in combination with surgery to keep a cancer from spreading to other parts of the body. Some widespread, fast-growing cancers are more difficult to treat. In these cases, chemotherapy may slow the growth of the cancer cells.

Doctors can tell if the chemotherapy is working by the results of medical tests. Physical examination, blood tests, and x rays are all used to check the effects of treatment on the cancer.

The possible outcomes of chemotherapy are:

• Complete remission or response. The cancer completely disappears for at least one month. The course of chemotherapy is completed and the patient is tested regularly for a recurrence.
• Partial response. The cancer shrinks in size by at least 30-50%, the reduction in size is maintained for at least one month, and no new lesions are found during treatment. The same chemotherapy may be continued or a different combination of drugs may be used.
• Minor response. The cancer shrinks 1-29%.
• Stabilization. The cancer does not grow or shrink. Other therapy options may be explored. A tumor may stay stabilized for many years.
• Progressive disease. The cancer continues to increase in size by at least 25%, or new lesions are noted. Other therapy options may be explored.
• A secondary malignancy may develop from the one being treated, and that second cancer may need additional chemotherapy or other treatment.

See Also Cancer biology; Clinical trials; Complementary cancer therapies; Fatigue; Fertility issues; Infection and sepsis; Memory change; Metastasis; Nutritional support; Pregnancy and cancer; Radiation therapy; Second cancers; Sexuality; Taste alteration; Vascular access

Resources

BOOKS

DeVita, Vincent T. et al, eds. Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2001.

Dollinger, Malin, Ernest H. Rosenbaum, and Greg Cable. Everyone's Guide to Cancer Therapy. Rev. 3rd ed. Kansas City, MO: Andrews McMeel Publishing, 1997.

Drum, David. Making the Chemotherapy Decision. Los Angeles, CA: Lowell House, 1996.

Haskell, Charles M. Cancer Treatment, 5th ed. Philadelphia, PA: W.B.Saunders Company, 2001.

McKay, Judith, and Nancee Hirano. The Chemotherapy Survival Guide. Oakland, CA: New Harbinger Publications, 1993.

Perry, Michael C. The Chemotherapy Source Book. 2nd ed. Baltimore, MD: Williams & Wilkins, 1996.

ORGANIZATION

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, GA 30329. 1-800-ACS-2345.

Cancer Information Service of the National Cancer Institute. 1-800-4-CANCER.

OTHER

American Cancer Society. "How Will the Chemotherapy BeAdministered?" 28 May 2001. <http://www3.cancer.org>.

American Cancer Society. Laryngeal and Hypopharyngeal Cancer Resource Center. "How Are Laryngeal and Hypopharyngeal Cancers Treated?" 28 May 2001. <http://www3.cancer.org>.

Cuesta-Romero, Carlos, and Grado-Pena, Jesus de. "Intralesional Methotrexate in Solitary Keratoacanthoma." Archives of Dermatology, April, 1998. 28 May 2001. <http://archderm.ama-assn.org/issues/v134n4/ffull/dIt0498-6.html>.

National Cancer Institute. National Institutes of Health."Chemotherapy and You: A Guide to Self-Help During Treatment." <http://www.cancernet.nci.nih.gov/chemotherapy/chemoint.html>.

OncoLink. "What is Chemotherapy?" University of PennsylvaniaCancer Center, September, 1997. <http://www.oncolink.upenn.edu/specialty/chemo/general/whatis_chemo.html>.

OncoLink. "Introduction to Chemotherapy." University of Pennsylvania Cancer Center, 1998. <http://www.oncolink.upenn.edu/specialty/chemo/general/chemo_intro.html>.

Toni Rizzo

Rhonda Cloos, R.N.

KEY TERMS

Adjuvant therapy

—Treatment given after surgery or radiation therapy when there is no further evidence of cancer to prevent the cancer from coming back.

Alkaloid

—A type of chemical commonly found in plants and often having medicinal properties.

Alykylating drug

—A drug that kills cells by directly damaging DNA.

Antiemetic

—A medicine that helps control nausea; also called an anti-nausea drug.

Antimetabolite

—A drug that interferes with a cell's growth or ability to multiply.

Combination chemotherapy

—The use of two or more anticancer drugs over the same course of treatment.

Lumbar puncture

—A procedure in which a person lies on his or her side and a doctor inserts a needle into the spinal column. It can be used to withdraw spinal fluid or to deliver chemotherapy into the spinal fluid.

Peritoneal cavity

—The space between the two layers of the peritoneum, the membrane that covers the abdominal wall of the body.

Platelets

—Blood cells that function in blood clotting.

Primary chemotherapy

—Chemotherapy that is the primary form of treatment. It may be used to shrink a tumor prior to surgically removing it.

QUESTIONS TO ASK THE DOCTOR

• What type of anticancer drugs will be used?
• Why were these drugs selected?
• How will the drugs be administered?
• Where will the chemotherapy take place?
• What preparation is necessary before treatment?
• What are the side effects?
• How can side effects be lessened?
• What are the symptoms of dangerous side effects?
• Who will give the chemotherapy?
• How often will the chemotherapy be given?
• How often are blood tests needed between treatments?
• What special care is needed while undergoing this type of treatment?
• When will the treatments be completed?
• What is the expected result?

Chemotherapy

Definition

Chemotherapy, sometimes referred to as "chemo," is the treatment of cancer with anticancer drugs.

Purpose

The main purpose of chemotherapy is to kill cancer cells. It usually is used to treat patients with cancer that has spread from the place in the body where it originated (metastasized). Chemotherapy destroys cancer cells anywhere in the body. It even kills cells that have broken off from the main tumor and traveled through the blood or lymph systems to other parts of the body.

Chemotherapy can cure some types of cancer. In some cases, it is used to slow the growth of cancer cells or to keep the cancer from spreading to other parts of the body. Chemotherapy may be given before surgery or radiation therapy to shrink the tumor (neoadjuvant therapy). When a cancer has been removed by surgery or treated with radiation therapy, chemotherapy may be used to keep the cancer from coming back (adjuvant therapy).

Once a remission is achieved, consolidation chemotherapy, also called intensification chemotherapy, is given to sustain a remission. Maintenance chemotherapy is chemotherapy given in lower doses as a treatment to prolong a remission in certain types of cancer. Chemotherapy also can ease the symptoms of cancer (palliative chemotherapy), helping some patients have a better quality of life.

Description

Chemotherapy for the treatment of cancer began in the 1940s with the use of nitrogen mustard. More than 100 chemotherapy drugs are now available to treat cancer, and many more are being tested for their ability to destroy cancer cells.

Most chemotherapy drugs interfere with the ability of cells to grow or multiply. Although these drugs affect all cells in the body, many useful treatments are most effective against rapidly growing cells. Cancer cells grow more quickly than most other body cells. Other cells that grow fast are cells of the bone marrow that produce blood cells, cells in the stomach and intestines, and cells of the hair follicles. Therefore, the most common side effects of chemotherapy are linked to the treatment's effects on other fast-growing cells.

Types of chemotherapy drugs

Chemotherapy drugs are classified according to how they work. The main types of chemotherapy drugs are:

• Alkylating drugs—kill cancer cells by directly attacking DNA, the genetic material of the genes. Cyclophosphamide is an alkylating drug.
• Antimetabolites—interfere with the production of DNA and keep cells from growing and multiplying. An example of an antimetabolite is 5-fluorouracil (5-FU).
• Antitumor antibiotics—made from natural substances such as fungi in the soil. They interfere with important cell functions, including production of DNA and cell proteins. Doxorubicin and bleomycin belong to this group of chemotherapy drugs.
• Plant alkaloids—prevent cells from dividing normally. Vinblastine and vincristine are plant alkaloids obtained from the periwinkle plant.
• Steroid hormones—slow the growth of some cancers that depend on hormones. For example, tamoxifen is used to treat breast cancers whose growth depends on the hormone estrogen.
• Topoisomerase inhibitors—interfere with the action of topoisomerase enzymes, the enzymes that control the part of DNA needed to multiply. Etoposide belongs to this group.

Biological therapy

Biological therapy, also called immunotherapy, consists of treatment with substances that boost the body's own immune system against cancer. The body usually produces these substances in small amounts to fight diseases. These substances can be made in the laboratory and given to patients to destroy cancer cells, change the way the body reacts to a tumor, or help the body repair or make new cells destroyed by chemotherapy.

Combination chemotherapy

Chemotherapy usually is given in addition to other cancer treatments, such as surgery and radiation therapy. When given with other treatments, it is called adjuvant chemotherapy. An oncologist decides on the specific chemotherapy drug or combination of drugs that will work best for each patient. The use of two or more drugs together—combination chemotherapy—often works better than using a single drug. Scientific studies of different drug combinations help doctors learn the combinations that work best for each type of cancer. For example, research in 2003 found that a combination of chemotherapy and gene therapy stopped breast cancer and its metastasis (spread to other organs or parts of the body).

Clinical trials

Some patients may be eligible to participate in clinical trials, research programs conducted with patients to evaluate a new drug, medical treatment, device, or combination of treatments. The purpose of clinical trials is to find new and improved methods of treating different diseases and special conditions. More information is available at the National Institutes of Health's clinical trials Web site, <www.clinicaltrials.gov> or by calling (888) FIND-NLM, (888) 346-3656 or (301) 594-5983. Another resource is the National Cancer Institute's Web site, <www.cancer.gov/clinicaltrials>.

Precautions

There are many different types of chemotherapy drugs. Oncologists, doctors who specialize in treating cancer, determine the drugs that are best suited for each patient. This decision is based on the type and severity of cancer, location of the cancer, patient's age and health, and other drugs the patient takes. Some patients should not be treated with certain chemotherapy drugs. Age and other conditions may affect the drugs selected for treatment. Heart disease, kidney disease, and diabetes are conditions that may limit the choice of treatment drugs. In 2003, research revealed that obesity appears to reduce the effectiveness of high-dose chemotherapy. Researchers said further study was needed to determine the best dosage for obese patients receiving therapy.

How chemotherapy is given

Chemotherapy is administered in different ways, depending on the drugs to be given and the type of cancer. Doctors determine the dose of chemotherapy drugs based on many factors, including the patient's height and weight.

Chemotherapy may be given by one or more of the following methods:

• orally (by mouth)
• injection
• through a catheter or port
• topically (via the skin)

Oral chemotherapy is given by mouth in the form of a pill, capsule, or liquid. This is the easiest method and can usually be done at home.

Intravenous (IV) chemotherapy is injected into a vein. A small needle is inserted into a vein on the hand or lower arm. The needle usually is attached to a small tube called a catheter, which delivers the drug to the needle from an IV bag or bottle.

Intramuscular (IM) chemotherapy is injected into a muscle. Chemotherapy given by intramuscular injection is absorbed into the blood more slowly than IV chemotherapy. Because of this, the effects of IM chemotherapy may last longer than chemotherapy given intravenously. Chemotherapy also may be injected subcutaneously (SQ or SC), which means under the skin. Injection of chemotherapy directly into the cancer is called intralesional (IL) injection.

Chemotherapy also may be given by a catheter or port permanently inserted into a central vein or body cavity. A port is a small reservoir or container that is placed in a vein or under the skin in the area where the drug will be given. These methods eliminate the need for repeated injections and may allow patients to spend less time in the hospital while receiving chemotherapy. A common location for a permanent catheter is the external jugular vein in the neck.

Intraperitoneal (IP) chemotherapy is administered into the abdominal cavity through a catheter or port. Chemotherapy given by catheter or port into the spinal fluid is called intrathecal (IT) administration. Catheters and ports also may be placed in the chest cavity, abdomen, bladder, or pelvis (intracavitary or IC catheter), depending on the location of the cancer to be treated.

Topical chemotherapy is given as a cream or ointment applied on the surface of the skin. This method is more common in treatment of certain types of skin cancers.

Treatment location and schedule

Patients may take chemotherapy at home, in the doctor's office, or as an inpatient or outpatient at the hospital. The choice of where to have chemotherapy depends on the drugs, delivery method, and sometimes the patient's and family's personal preferences. Most patients receive chemotherapy as an outpatient. Some patients stay in the hospital when first beginning chemotherapy, so their doctor can check for any side effects and change the dose if needed.

Frequency and length of chemotherapy treatment depends on the form of cancer, types of drugs, how the patient responds to the treatment, and the patient's health and ability to tolerate the drugs. Chemotherapy administration may take only a few minutes or as long as several hours. Chemotherapy may be given daily, weekly, or monthly. A rest period may follow a course of treatment before the next course begins, allowing new cells to grow and the patient to recover and regain strength. In combination chemotherapy, more than one drug may be given at a time, or the drugs may be given alternately, one following the other.

Maintaining the prescribed treatment schedule is essential to ensuring that the drugs work properly. The doctor should be contacted as soon as possible if a treatment session is missed, or a dose of the drug is skipped, for whatever reasons. Sometimes the doctor may need to delay a treatment based on the results of certain blood tests. Specific instructions will be provided if a treatment delay becomes necessary.

Preparation

TESTS A number of medical tests are done before chemotherapy is started. The results of x rays , other imaging tests, and tumor samples taken during biopsy or surgery will help the oncologist determine how much the cancer has spread.

Blood tests give the doctor important information about the function of the blood cells and levels of chemicals in the blood. A complete blood count (CBC) is commonly done before and regularly during treatment. The CBC shows the numbers of white blood cells, red blood cells, and platelets in the blood. Because chemotherapy affects the bone marrow, where blood cells are made, levels of these cells often drop during chemotherapy. The white blood cells and platelets are most likely to be affected by chemotherapy. A drop in the white blood cell count means the immune system cannot function properly. Low levels of platelets can cause a patient to bleed easily from a cut or other wound. A low red blood cell count can lead to anemia (deficiency of red blood cells) and fatigue.

INFORMED CONSENT Informed consent is an educational process between health care providers, patients, and/or their legal guardians. Before any procedure is performed or any form of medical care is provided, the patient and parents (if the patient is under age 18), are asked to sign a consent form, which provides permission for the child to receive chemotherapy treatment. The health care provider will review the informed consent form with the parents before they are asked to sign it. Before signing the form, the patient and parents should understand the nature and purpose of the treatment, its risks and benefits, and alternatives, including the option of not proceeding with the treatment. During the discussion about treatment, the health care providers are available to answer the patient's and parents' questions about the consent form or course of treatment.

PREPARING FOR THE TREATMENT When a chemotherapy treatment takes a long time, the patient may prepare for it by wearing comfortable clothes. Packing a book, favorite game, or an audiotape may help pass the time and ease the stress of receiving chemotherapy.

Usually parents stay with their child during the treatment. It is necessary to drive the child home (even if he or she is old enough to drive), since the medications taken to control nausea and the chemotherapy treatment itself can cause drowsiness.

ANTI-EMETIC DRUGS Sometimes, patients taking chemotherapy drugs known to cause nausea are given medications called anti-emetics before chemotherapy is administered. Anti-emetic drugs help to lessen feelings of nausea. Two anti-nausea medications that may be used are Kytril and Zofran. To decrease nausea from occurring just after a chemotherapy session, the child should not eat for about two hours before the treatment appointment.

Research published in 2003 revealed that taking melatonin, a natural hormone substance, may help improve chemotherapy's effectiveness and reduce the toxic effects of the drugs.

Aftercare

Tips for helping to control side effects after chemotherapy include:

• following any instructions given by the doctor or nurse
• taking all prescribed medications
• eating small amounts of bland foods
• maintaining good nutrition by getting enough calories, including protein in the diet, and taking a daily multivitamin (as recommended by the child's physician)
• drinking at least eight cups of fluids per day
• getting plenty of rest
• exercising regularly

Some patients find it helpful to breathe fresh air or get mild exercise , such as taking a walk.

Side effects and their severity are not indicators of how well the chemotherapy is working, since they vary greatly among patients and from drug to drug. Tests and exams can help determine the effectiveness of the chemotherapy.

Risks

Chemotherapy drugs are toxic to normal cells as well as cancer cells. A dose that will destroy cancer cells will probably cause damage to some normal cells. Doctors adjust doses to do the least amount of harm possible to normal cells. Side effects are temporary, and damaged non-cancerous cells will be replaced with healthy cells.

Some patients feel few or no side effects, and others may have more serious side effects. In some cases, a dose adjustment is all that is needed to reduce or stop a side effect. The types and severity of side effects depend on the chemotherapy drugs, dose, length of therapy, the body's reaction to the drug, and the child's overall health at the start of chemotherapy.

Some chemotherapy drugs have more side effects than others. Among the most common side effects are:

• fatigue
• nausea and vomiting
• loss of appetite
• diarrhea
• hair loss
• anemia
• infection
• easy bleeding or bruising
• sores in the mouth and throat
• neuropathy and other damage to the nervous system
• kidney damage

Fatigue (feeling tired and lacking energy) is the most common side effect of cancer and chemotherapy medications. Fatigue gradually goes away as the cancer responds to treatment. To help a child cope with fatigue, parents should plan rest periods, provide nutritious meals to maintain energy and meet caloric needs, limit caffeine , and encourage exercise and activity.

Nausea and vomiting are common, but can usually be controlled by taking anti-nausea drugs; consuming adequate fluids; drinking fluids at least one hour before or after a meal; eating and drinking slowly, chewing food completely; eating smaller meals throughout the day; choosing high-carbohydrate, low-fat foods; and avoiding sweet, fried, or spicy foods. When vomiting episodes stop, the child may feel better after eating easy-to-digest and bland foods such as clear liquids, crackers, gelatin, and plain toast.

Loss of appetite may be due to nausea, changes in taste and smell, or the stress of undergoing cancer treatment. To help maintain the child's appetite, meals and snacks should be small rather than large. Food should be served when the child is hungry, and he or she should be offered favorite foods. It is recommended that children help select and prepare foods. Calories may be boosted by offering high-calorie and high-protein snacks and foods. Sometimes a feeding tube may be needed to maintain a child's weight or for children who cannot eat or drink.

If the child has diarrhea, high-fiber and high-fat foods, gassy foods, and carbonated beverages should be avoided. It is important for the child to continue drinking fluids throughout the day to avoid dehydration from diarrhea or vomiting.

Some chemotherapy drugs cause hair loss, but it is almost always temporary. The doctor can advise the parents and patients if hair loss is expected with the type of chemotherapy drug to be given. When hair loss occurs, it may begin after a few treatments, or several weeks after the first treatment. To care for the scalp and hair during chemotherapy, the child should use a mild shampoo and soft brush, and low heat for hair drying. The head should be protected from heat and sun with a hat or scarf. If desired, a wig or hair piece may be worn.

Low blood cell counts caused by the effect of chemotherapy on the bone marrow can lead to anemia, infections, and easy bleeding and bruising. Patients with anemia have too few red blood cells to deliver oxygen and nutrients to the body's tissues. Anemic patients feel tired and weak, are short of breath, and may have a rapid heartbeat. If red blood cell levels fall too low, a blood transfusion may be given.

Patients receiving chemotherapy are more likely to acquire infections because their infection-fighting white blood cells are reduced. It is important to take measures to avoid infections. When the white blood cell count drops too low, the doctor may prescribe medications called colony stimulating factors, which help white blood cells grow. Neupogen and Leukine are two colony stimulants that help fight infection. To reduce the risk of infection, thorough and frequent hand washing and safe food preparation are essential.

Platelets are blood cells that make the blood clot. When patients do not have enough platelets, they may bleed or bruise easily, even from small injuries. Patients with low blood platelets should take precautions to avoid injuries. Medicines such as aspirin and other pain relievers can affect platelets and slow down the clotting process.

Chemotherapy can cause irritation and dryness in the mouth and throat. Painful sores may form that can bleed and become infected. To help avoid mouth sores and irritation, the child should have a dental cleaning before chemotherapy begins, take care of the teeth and gums by brushing and flossing after every meal with a soft brush, rinse with a solution of baking soda and water, and avoid mouth washes or rinses that contain salt or alcohol. After use, the toothbrush should be rinsed thoroughly and stored in a dry place.

To help the child cope with a dry mouth, parents should encourage him or her to drink plenty of liquids. Popsicles or lollipops offer relief. Soft foods may be prepared, and dry foods may be moistened with sauce, butter, or gravy.

Tiredness, confusion, and depression can occur from chemotherapy's effect on certain central nervous system functions. The doctor should be notified if these symptoms occur.

Tests will be performed to monitor the effects of chemotherapy medications on the patient's kidneys and liver. Monitoring kidney and liver function helps to avoid potential damage or complications.

Normal results

The main goal of chemotherapy is to cure cancer. In fact, many cancers are cured by chemotherapy. Chemotherapy may be used in combination with surgery to keep a cancer from spreading to other parts of the body. Some widespread, fast-growing cancers are more difficult to treat. In these cases, chemotherapy may slow the growth of cancer cells.

The results of medical tests provide information so doctors can tell if the chemotherapy is working. Physical examination, blood tests, and x rays are used to check the effects of treatment on the cancer.

The possible outcomes of chemotherapy are:

• Complete remission or response. The cancer completely disappears; there is no evidence of disease. The course of chemotherapy is completed and the patient is tested regularly for a recurrence.
• Partial remission or response. The cancer shrinks in size but does not disappear. The same chemotherapy may be continued or a different combination of drugs may be given.
• Stabilization. The cancer does not grow or shrink. Other therapy options may be explored. A tumor may stay stabilized for many years.
• Progression. The cancer continues to grow. Other therapy options may be explored.
• A secondary malignancy may develop from the one being treated, and that second cancer may need additional chemotherapy or other treatment.

Parental concerns

Some important questions parents can ask about their child's course of chemotherapy include:

• What specific drugs will be given?
• How will the drugs be administered, and where will they be given?
• What are the potential benefits and risks of these drugs?
• What are some other possible treatments for the child's type of cancer?
• What is the standard care for the child's type of cancer?
• Are there any applicable clinical trials currently enrolling children?
• How many treatments will be needed? How long will they last?
• What are the potential side effects? When might they occur? How can they be treated or relieved? How serious are they likely to be? What side effects should be reported to the child's doctor?
• Can the child take other prescription or over-the-counter medications while receiving chemotherapy?
• What activities should be restricted or limited during the course of treatment?
• What is the long-term effect of chemotherapy?

Most school-age children can continue to go to school while receiving chemotherapy. However, the school schedule may need adjustment according to how the child feels and what side effects he or she experiences. During the cold and flu season, it may be best to keep the child home to prevent infection. If possible, treatments should be scheduled on a day when there is no school the next day, to provide time to recover.

To reduce the child's exposure to colds and illnesses and to help the child avoid infection:

• The child should avoid crowded areas, such as shopping malls.
• The child and entire family should be encouraged to wash hands frequently.
• People who are sick should be avoided, and they should be asked to refrain from visiting until they are healthy.
• The child should stay away from children who have recently received live virus vaccines such as chicken pox and oral polio since they may be contagious to people with a low blood cell count.
• Contact with animal litter boxes and waste, bird cages, and fish should be prevented.
• Contact with standing water, such as bird baths, flower vases, or humidifiers, should be prevented.
• Food must be safely prepared and cooked thoroughly to avoid food-borne illnesses.
• Parents should check with the child's doctor before scheduling immunizations, flu, or pneumonia vaccines.

Aspirin and products containing aspirin should be avoided, as they can affect platelet counts. Parents should check with the child's doctor before giving any vitamins , herbal supplements, and any over-the-counter medications.

The child's doctor should provide specific activity guidelines, including recommendations regarding the child's sports participation. Contact sports may be discouraged to reduce the risk of injury.

Treatment and care for a child with cancer can be costly, and some health insurance plans may not cover all expenses associated with a child's hospitalization or treatment. Help is available to cover medical expenses. The parents can discuss financial aid with the hospital. Some organizations provide financial assistance to children in need of chemotherapy or other cancer treatments.

Caring for a child with cancer is demanding. Support groups are available to help parents and caregivers cope with the challenges of providing care for children with special medical needs. It is important for parents to take care of themselves, too, by eating properly, exercising regularly, taking care of personal hygiene, keeping in contact with friends and family members for support, and managing stress by practicing relaxation techniques.

When to call the doctor

If a child has any of these symptoms, the parent or caregiver should call the child's doctor right away, as they could indicate an infection, blood clotting problem, or effect on the central nervous system:

• abdominal pain, vomiting, or diarrhea that awakens the child during the night
• persistent or severe abdominal pain, vomiting, or diarrhea
• unexplained weight loss
• fever
• chills or sweating
• frequent urgency to urinate, burning during urination, or change in color of urine
• rectal bleeding, or black or bloody bowel movements
• severe cough or sore throat
• redness, swelling, or tenderness, especially around a wound or sore
• earaches, headaches, or stiff neck
• mouth sores, or blisters on the lips or skin
• sinus pain or pressure
• headaches
• changes in vision
• unexplained bleeding or bruising
• red spots under the skin
• confusion
• persistent depressed mood
• worsening overall health

KEY TERMS

Adjuvant therapy —A treatment that is intended to aid primary treatment.

Alkaloid —A type of chemical commonly found in plants and often having medicinal properties.

Alkylating agent —A chemical that alters the composition of the genetic material of rapidly dividing cells, such as cancer cells, causing selective cell death; used as a chemotherapeutic agent.

Alopecia —The loss of hair, or baldness.

Anti-emetic —A preparation or medication that relieves nausea and vomiting. Cola syrup, ginger, and motion sickness medications are examples of antiemetics.

Antimetabolite —A drug or other substance that interferes with a cell's growth or ability to multiply.

Benign —In medical usage, benign is the opposite of malignant. It describes an abnormal growth that is stable, treatable, and generally not life-threatening.

Blood cell count —The number of red blood cells, white blood cells, and platelets in a sample of blood. Also called a complete blood count (CBC).

Bone marrow —The spongy tissue inside the large bones in the body that is responsible for making the red blood cells, most white blood cells, and platelets.

Catheter —A thin, hollow tube inserted into the body at specific points in order to inject or withdraw fluids from the body.

Chest x ray —Brief exposure of the chest to radiation to produce an image of the chest and its internal structures.

Infusion —Introduction of a substance directly into a vein or tissue by gravity flow.

Lymph nodes —Small, bean-shaped collections of tissue located throughout the lymphatic system. They produce cells and proteins that fight infection and filter lymph. Nodes are sometimes called lymph glands.

Malignant —Cells that have been altered such that they have lost normal control mechanisms and are capable of local invasion and spread to other areas of the body. Often used to describe a cancer.

Metastatic —The term used to describe a secondary cancer, or one that has spread from one area of the body to another.

Platelet —A cell-like particle in the blood that plays an important role in blood clotting. Platelets are activated when an injury causes a blood vessel to break. They change shape from round to spiny, "sticking" to the broken vessel wall and to each other to begin the clotting process. In addition to physically plugging breaks in blood vessel walls, platelets also release chemicals that promote clotting.

Radiation therapy —A cancer treatment that uses high-energy rays or particles to kill or weaken cancer cells. Radiation may be delivered externally or internally via surgically implanted pellets. Also called radiotherapy.

Red blood cells —Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.

Remission —A disappearance of a disease and its symptoms. Complete remission means that all disease is gone. Partial remission means that the disease is significantly improved, but residual traces of the disease are still present. A remission may be due to treatment or may be spontaneous.

Tumor —A growth of tissue resulting from the uncontrolled proliferation of cells.

White blood cells —A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system; they fight infection.

Resources

BOOKS

Fischer, David A., et al. The Cancer Chemotherapy Handbook. London: C.V. Mosby, 2003.

McKay, Judith, and Nancee Hirano. The Chemotherapy and Radiation Therapy Survivor's Guide, 2nd ed. Oakland, CA: New Harbinger Publications, 1998.

Skeel, Roland T. K. Handbook of Cancer Chemotherapy, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2003.

PERIODICALS

"Chemotherapy and You: A Guide to Self-Help During Cancer Treatment." National Institutes of Health, National Cancer Institute. NIH Publication No. 03-1136, 2003.

"Gene Therapy and Chemotherapy Combine to Stop Breast Cancer and its Metastasis." Gene Therapy Weekly (Oct. 30, 2003): 2.

"Melatonin Improves the Efficacy of Chemotherapy and Quality of Life" Biotech Week (Sept. 10, 2003): 394.

"Obesity May Reduce Efficacy of High-Dose Chemotherapy." Health Medicine Week (Aug. 11, 2003): 385.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA 30329-4251. (800) 227-2345 or (404) 320-3333. Web site:<www.cancer.org>.

Cancercare. (800) 813-4673. Web site: <www.cancercare.org>.

National Cancer Institute. U.S. National Institutes of Health. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 422-6237. Web site: <www.cancer.gov>.

WEB SITES

CancerAnswers. Available online at: <www.canceranswers.com>.

Chemocare.com. Available online at: <www.chemocare.com>.

OncoLink. University of Pennsylvania Cancer Center. Available online at: <www.oncolink.upenn.edu>.

Planet Cancer. Available online at: <www.planetcancer.org>.

Toni Rizzo Teresa G. Odle Angela M. Costello

Chemotherapy

Chemotherapy is the controlled use of chemicals for a medicinal purpose. The term was coined by the German bacteriologist Paul Ehrlich, around 1900, when he examined aniline dyes and arsenicals as possible treatments for diseases such as trypanosomiasis and syphilis. He envisioned "magic bullets" that could target invading organisms and leave the host unscathed. This goal of providing therapeutic benefits with minimal side effects continues in all areas of drug development. Remarkable successes have been obtained in compounds that modulate normal biochemistry within the human body. These include analgesics , antihistamines, cardiac rhythm regulators, blood pressure modifiers, anesthetics, anti-inflammatory agents, sedatives, diuretics, and vasodilators. In the battle against the unwanted growth of invading organisms and mutated cells (cancer), the greatest successes have occurred in the bacterial antibiotics; in the twentieth century they have increased human longevity more than any other medication. Similar successes for drugs treating viral infections and cancer have been elusive.

In recent years chemotherapy has become a popular form of anticancer treatment. The goal of a magic bullet endures, but it is often difficult to attain because most of chemotherapy's useful agents are poisonous. This results from the similarities between cancerous cells and normal cells. Drugs that kill tumors are not specific enough to leave normal cells unharmed. Therefore, virtually all cancer chemotherapy is a delicate compromise between effectiveness and toxicity, resulting in significant side effects. Patients and physicians accept this because the alternatives are limited and the progression of the often fatal disease usually occurs more quickly without some intervening form of chemotherapy treatment.

The pursuit of chemical agents that can more effectively treat cancer has led to many decades of research by a multitude of chemists, biochemists, microbiologists, biologists, and research physicians. Thousands of chemicals have been synthesized and tested in tissue cultures and animal models. Only a modest number have proved to be useful in treating humans, but they have become the mainstay of the chemotherapeutic attack on cancer. In combination with early detection, surgery, radiation, and newly developing immunotherapies and targeted therapies, the judicious use of chemotherapy can kill tumors and limit their recurrence.

Common Agents

The most active chemotherapeutic agents fall into a small number of broad categories depending on their mode of action: alkylating/cross-linking agents that interact with DNA ; antibiotics that can kill mammalian cells instead of bacteria; antimetabolites/inhibitors that interfere with normal biochemistry; hormones that interact with receptors on tumor cells; and cytokines that can alter the balance of the intercellular communication system. Some commonly used agents, and their classifications, are listed in Table 1.

All these drugs, more generally, can be classified as either reactive or interactive. In the first case, biological activity depends on the chemical reaction of the drug with a target molecule. The resulting adduct interferes with normal cellular processes and may enhance cell death. Such reactive molecules are often indiscriminant, however, and are prone to powerful side effects. In the second case, biological activity depends only on the drug's structure, allowing it to interfere with cellular pathways that depend on lock-and-key recognition processes. These interactions can often be very specific, but may be limited in efficacy due to the existence of parallel pathways for most critical processes.

Reactions with DNA are prototypical of reactive anticancer chemicals. Alkylating and cross-linking agents such as nitrogen mustards, platinum compounds, alkane sulfonates, nitrosoureas, and methylating agents are believed to achieve their therapeutic effect by irreversibly binding to DNA and blocking its replication. This class of drugs is used routinely to treat most forms of cancer: sarcoma, carcinoma, teratoma, and leukemia.

Naturally occurring antibiotics (i.e., produced by other organisms) are complicated, multipurpose compounds. They often contain unsaturated polycyclic rings that can squeeze between DNA bases (intercalation) and interrupt DNA replication; quinone redox sites that can create free radicals

in the cell; and electrophilic moieties that can alkylate the guanine of DNA. They are used routinely in the treatment of leukemia, germ cell tumors of the testis and ovary, lymphomas, and some childhood cancers.

Antimetabolites substitute for naturally occurring compounds in normal metabolism and biosynthesis reactions. They are designed to interfere with the normal biochemistry of a cell by deactivating or retarding enzyme action or by replacing normal nucleic acids in DNA and RNA with analogs that inhibit replication or repair. Special classes of inhibitory molecules include the microtubule-targeting drugs and topoisomerase inhibitors, which interfere with specific targets within a cell. They are used routinely in all forms of cancer, usually in combination with each other and with the alkylating/cross-linking agents.

Hormones and hormone receptor inhibitors can be administered because some tumors have hormone receptors. The response of the tumor to such therapy, however, is difficult to predict. It can be detrimental or beneficial depending on the hormone, the type of cancer, and even the individual. These drugs are used routinely to treat breast cancer patients with receptor-positive tumor types.

Cytokines, like hormones, are interactive molecules. They bind to receptors on either effector cells of the immune system or the tumor cells themselves. In doing so, they activate programs within the cells that may be useful at a particular time and location in killing the tumor or attracting immune killer cells. A special class of immune system cytokines, called interleukins, has been tested in melanoma and renal carcinoma with some encouraging results. Although cytokines are still largely experimental, their use is growing due to increased understanding of the complex signaling of the immune system.

Kinetics

To understand why chemical compounds are useful drugs in treating diseases like cancer, scientists study their complicated kinetics within the human body. The first concern is their rate of reaction or target binding affinities with other biological compounds. The second is their rate of distribution and excretion . Together, these are referred to as pharmacokinetics. This is part of a broader series of effects, referred to as pharmacodynamics, which include the positive and negative physiological changes induced by a drug. When a drug is administered (orally or by injection), it must reach the desired target in the organism before it is excreted or altered by detoxifying enzymes (usually located in the liver). Studies using radioactive forms of drugs have been used as tracers to follow both the chemical modifications and their distributions in various compartments of the body. Results have allowed the synthesis of new drugs with better chemistries, distributions, and toxicity profiles.

The most useful reactive drugs are those that have biologically relevant reaction rates. This means that they react slowly enough to reach their targets but fast enough to damage target cells before they are cleared. This appears to be a simple concept for drug design, but the immense number of reactions that can occur in a biological environment have made the discovery and development of such drugs a tedious procedure.

A successful strategy for achieving this kinetic balance is to use a compound that has a long-lived intermediate form which keeps it near its target. Two widely used drugs, cyclophosphamide and cisplatin, are good examples of this, but for different reasons.

In cyclophosphamide, the nitrogen mustard moiety of the parent compound is unreactive because the electron-withdrawing property of the ring reduces the reactivity of the lone pair of nitrogen electrons. The result is a drug that is both nontoxic and nontherapeutic. As the drug circulates in the bloodstream, liver enzymes (cytochrome P450) oxidize the 4th position of the ring (see Figure 1). The 4-OH form undergoes nonenzymatic cleavage of the acyclic tautomer, forming a phosphoramide mustard. This last step occurs slowly enough for the 4-OH form to leave the liver and enter other cells. Once the charged product forms, it cannot escape the cells that it enters. The chloro-ethyl side groups then cyclize sequentially into highly reactive aziridinium forms, which attack and cross-link DNA, leading to cell death.

In cisplatin, the +2 oxidation state of the platinum atom forms four coordination bonds in a square plane. Each ammine supplies two electrons

from the filled orbital of nitrogen, while each chloride anion supplies two electrons and one negative charge that neutralizes the molecule. The result is a molecule stable to nucleophilic attack and able to cross cell membranes due to its charge neutrality. In the presence of low chloride, such as inside a cell, the chlorides begin to leave the platinum at a slow rate (a half-life of 5–6 hours). They are replaced by water molecules forming first mono-aquo and then di-aquo species, which are singly and doubly charged, respectively. These forms cannot penetrate the cell membrane and are confined inside the cell. Water makes a much better leaving group than Cl⁻, resulting in rapid reactions with intracellular nucleophiles. With two sites of attack, the cross-linking of protein and DNA occurs readily.

In the case of interactive drugs, the most useful are those that exhibit long-term biological stability which allows them to reach their targets before they are degraded. They also have very high affinities for their targets so they can block normal molecules from binding. Many of these have been extracted from fungi, bacteria, and plants. Years of evolution have fine-tuned these complex molecules into effective poisons that have been targeted against the predators of these organisms. In humans, many have shown remarkable antitumor properties with manageable toxicities. Others have been chemically modified to give them the necessary pharmacokinetic properties suitable for fighting cancer. It is believed that many more of these molecules remain to be discovered and that much will be learned by studying their mechanisms of action.

Specificity

Many successful drugs have shown specificity for certain tumors. The reason for this selectivity is usually not obvious, since the expected mechanisms of action often suggest that they would kill all cells equally well. In fact, many do harm normal cells, leading to the unpleasant side effects that most patients experience. Nonetheless, such drugs can be effective in reducing or eliminating large tumors while sparing the patient.

The specificity of a given drug for a particular tumor has largely been discovered by trial and error on patients enrolled in clinical trials. In many cases, the reasons for that specificity are still unknown but appear to result from the different biochemistries of tumor cells. In particular, the regulatory pathways in tumor cells are dramatically out of balance. This is often the result of several mutations in oncogenes and suppressor genes disabling the control elements of cell division and homeostasis. DNA replication accelerates and remains unwrapped longer, exposing it to more cross-linking. In some tumors, DNA repair enzymes are expressed at reduced levels, allowing damage to accumulate faster. There is also evidence that many active agents shift the unbalanced regulation of tumor cells into apoptosis (programmed cell death), causing the tumor to essentially commit suicide. These various lines of research show that although tumor cells are aggressive and uncontrolled, they are also vulnerable to the right kind of attack.

The continuing goal of mechanism-of-action and specificity research is to provide a better understanding of the interaction between drugs and tumor cells. This will allow the rational design of new drugs that are lower in toxicity and higher in effectiveness. As cellular targets are identified, as new proteins are characterized from the human genome project, as cell–cell communication pathways are elucidated, and as high-power computation is established, rational drug design will become more practical. Future chemotherapy will likely be targeted, individualized therapy, where patients will be fitted to therapies just as they would be to finely tailored clothes.

see also Coordination Compounds; Ehrlich, Paul.

David A. Juckett

Bibliography

Berkow, Robert, ed. (1997). The Merck Manual of Medical Information: Home Edition. Whitehouse Station, NJ: Merck Research Laboratories.

Drews, Jurgen (2000). "Drug Discovery: A Historical Perspective." Science 287:1960–1964.

Gibbs, J. B. (2000). "Mechanism-Based Target Identification and Drug Discovery in Cancer Research." Science 287:1969–1973.

Hardman, Joel; Limbird, Lee; and Gilman, Alfred, eds. (2002). Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill.

Perry, Michael C., ed. (2001). The Chemotherapy Source Book, 3rd edition. Philadelphia: Lippincott Williams & Wilkins.

Schreiber, Stuart L. (2000). "Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery." Science 287:1964–1969.

Workman, Paul, and Kaye, Stanley B. (2002). "Translating Basic Cancer Research into New Cancer Therapeutics." Trends in Molecular Medicine 8(4) (Suppl.): S1–S9.

Internet Resources

"Chemotherapy and You: A Guide to Self-Help During Cancer Treatment." National Cancer Institute. Available from <http://www.nci.nih.gov/cancerinfo/chemotherapy-and-you>.

"Specific Chemotherapy Drugs." Cancer Information and Support International. Available from <http://www.cancer-info.com/chemotypes.htm>.

Chemotherapy

Definition

Chemotherapy is treatment of cancer with anticancer drugs.

Purpose

The main purpose of chemotherapy is to kill cancer cells. It usually is used to treat patients with cancer that has spread from the place in the body where it started (metastasized). Chemotherapy destroys cancer cells anywhere in the body. It even kills cells that have broken off from the main tumor and traveled through the blood or lymph systems to other parts of the body.

Chemotherapy can cure some types of cancer. In some cases, it is used to slow the growth of cancer cells or to keep the cancer from spreading to other parts of the body. When a cancer has been removed by surgery, chemotherapy may be used to keep the cancer from coming back (adjuvant therapy). Chemotherapy also can ease the symptoms of cancer, helping some patients have a better quality of life.

Precautions

There are many different types of chemotherapy drugs. Oncologists, doctors who specialize in treating cancer, determine which drugs are best suited for each patient. This decision is based on the type of cancer, the patient's age and health, and other drugs the patient is taking. Some patients should not be treated with certain chemotherapy drugs. Age and other conditions may affect the drugs with which a person may be treated. Heart disease, kidney disease, and diabetes are conditions that may limit the choice of treatment drugs. In 2003, research revealed that obesity appears to reduce the effectives of high-dose chemotherapy. Researchers said further study was needed to determine the best dosage for obese patients receiving therapy.

Description

More than 50 chemotherapy drugs are currently available to treat cancer and many more are being tested for their ability to destroy cancer cells. Most chemotherapy drugs interfere with the ability of cells to grow or multiply. Although these drugs affect all cells in the body, many useful treatments are most effective against rapidly growing cells. Cancer cells grow more quickly than most other body cells. Other cells that grow fast are cells of the bone marrow that produce blood cells, cells in the stomach and intestines, and cells of the hair follicles. Therefore, the most common side effects of chemotherapy are linked to the treatment's effects on other fast growing cells.

Types of chemotherapy drugs

Chemotherapy drugs are classified based on how they work. The main types of chemotherapy drugs are described below:

• Alkylating drugs kill cancer cells by directly attacking DNA, the genetic material of the genes. Cyclophosphamide is an alkylating drug.
• Antimetabolites interfere with the production of DNA and keep cells from growing and multiplying. An example of an antimetabolite is 5-fluorouracil (5-FU).
• Antitumor antibiotics are made from natural substances such as fungi in the soil. They interfere with important cell functions, including production of DNA and cell proteins. Doxorubicin and bleomycin belong to this group of chemotherapy drugs.
• Plant alkaloids prevent cells from dividing normally. Vinblastine and vincristine are plant alkaloids obtained from the periwinkle plant.
• Steroid hormones slow the growth of some cancers that depend on hormones. For example, tamoxifen is used to treat breast cancers that depend on the hormone estrogen for growth.

Combination chemotherapy

Chemotherapy usually is given in addition to other cancer treatments, such as surgery and radiation therapy. When given with other treatments, it is called adjuvant chemotherapy. An oncologist decides which chemotherapy drug or combination of drugs will work best for each patient. The use of two or more drugs together often works better than a single drug for treating cancer. This is called combination chemotherapy. Scientific studies of different drug combinations help doctors learn which combinations work best for each type of cancer. For example, new research in 2003 found that a combination of chemotherapy and gene therapy stopped breast cancer and its metastasis (spread to other organs or parts of the body).

How chemotherapy is given

Chemotherapy is administered in different ways, depending on the drugs to be given and the type of cancer. Doctors decide the dose of chemotherapy drugs considering many factors, among them being the patient's height and weight.

Chemotherapy may be given by one or more of the following methods:

• orally
• by injection
• through a catheter or port
• topically

Oral chemotherapy is given by mouth in the form a pill, capsule, or liquid. This is the easiest method and can usually be done at home.

Intravenous (IV) chemotherapy is injected into a vein. A small needle is inserted into a vein on the hand or lower arm. The needle usually is attached to a small tube called a catheter, which delivers the drug to the needle from an IV bag or bottle.

Intramuscular (IM) chemotherapy is injected into a muscle. Chemotherapy given by intramuscular injection is absorbed into the blood more slowly than IV chemotherapy. Because of this, the effects of IM chemotherapy may last longer than chemotherapy given intravenously. Chemotherapy also may be injected subcutaneously (SQ or SC), which means under the skin. Injection of chemotherapy directly into the cancer is called intralesional (IL) injection.

Chemotherapy also may be given by a catheter or port permanently inserted into a central vein or body cavity. A port is a small reservoir or container that is placed in a vein or under the skin in the area where the drug will be given. These methods eliminate the need for repeated injections and may allow patients to spend less time in the hospital while receiving chemotherapy. A common location for a permanent catheter is the external jugular vein in the neck. Intraperitoneal (IP) chemotherapy is administered into the abdominal cavity through a catheter or port. Chemotherapy given by catheter or port into the spinal fluid is called intrathecal (IT) administration. Catheters and ports also may be placed in the chest cavity, bladder, or pelvis, depending on the location of the cancer to be treated.

Topical chemotherapy is given as a cream or ointment applied directly to the cancer. This method is more common in treatment of certain types of skin cancer.

Treatment location and schedule

Patients may take chemotherapy at home, in the doctor's office, or as an inpatient or outpatient at the hospital. Most patients stay in the hospital when first beginning chemotherapy, so their doctor can check for any side effects and change the dose if needed.

How often and how long chemotherapy is given depends on the type of cancer, how patients respond to the drugs, patients' health and ability to tolerate the drugs, and the types of drugs given. Chemotherapy administration may take only a few minutes or may last as long as several hours. Chemotherapy may be given daily, weekly, or monthly. A rest period may follow a course of treatment before the next course begins. In combination chemotherapy, more than one drug may be given at a time, or they may be given alternately, one following the other.

Preparation

A number of medical tests are done before chemotherapy is started. The oncologist will determine how much the cancer has spread from the results of x rays and other imaging tests and from samples of the tumor taken during surgery or biopsy.

Blood tests give the doctor important information about the function of the blood cells and levels of chemicals in the blood. A complete blood count (CBC) is commonly done before and regularly during treatment. The CBC shows the numbers of white blood cells, red blood cells, and platelets in the blood. Because chemotherapy affects the bone marrow, where blood cells are made, levels of these cells often drop during chemotherapy. The white blood cells and platelets are most likely to be affected by chemotherapy. A drop in the white blood cell count means the immune system cannot function properly. Low levels of platelets can cause a patient to bleed easily from a cut or other wound. A low red blood cell count can lead to anemia (deficiency of red blood cells) and fatigue.

When a chemotherapy treatment takes a long time, the patient may prepare for it by wearing comfortable clothes. Bringing a book to read or a tape to listen to may help pass the time and ease the stress of receiving chemotherapy. Some patients bring a friend or family member to provide company and support during treatment.

Sometimes, patients taking chemotherapy drugs known to cause nausea are given medications called anti-emetics before chemotherapy is administered. Anti-emetic drugs help to lessen feelings of nausea. Two anti-nausea medications that may be used are Kytril and Zofran.

Other ways to prepare for chemotherapy and help lessen nausea are:

• regularly eating nutritious foods and drinking lots of fluids
• eating and drinking normally until about two hours before chemotherapy
• eating high carbohydrate, low-fat foods and avoiding spicy foods

New research also revealed in 2003 that taking melatonin, a natural hormone substance, may help improve chemotherapy's effectiveness and reduce the toxic effects of the drugs.

Aftercare

Tips for helping to control side effects after chemotherapy include:

• Following any instructions given by the doctor or nurse
• Taking all prescribed medications
• Eating small amounts of bland foods
• Drinking lots of fluids
• Getting plenty of rest.

Some patients find it helps to breathe fresh air or get mild exercise, such as taking a walk.

Risks

Chemotherapy drugs are toxic to normal cells as well as cancer cells. A dose that will destroy cancer cells will probably cause damage to some normal cells. Doctors adjust doses to do the least amount of harm possible to normal cells. Some patients feel few or no side effects, and others may have more serious side effects. In some cases, a dose adjustment is all that is needed to reduce or stop a side effect.

Some chemotherapy drugs have more side effects than others. Some of the most common side effects are:

• nausea and vomiting
• loss of appetite
• hair loss
• anemia and fatigue
• infection
• easy bleeding or bruising
• sores in the mouth and throat
• neuropathy and other damage to the nervous system
• kidney damage

Nausea and vomiting are common, but can usually be controlled by taking antinausea drugs, drinking enough fluids, and avoiding spicy foods. Loss of appetite may be due to nausea or the stress of undergoing cancer treatment.

Some chemotherapy drugs cause hair loss, but it is almost always temporary.

Low blood cell counts caused by the effect of chemotherapy on the bone marrow can lead to anemia, infections, and easy bleeding and bruising. Patients with anemia have too few red blood cells to deliver oxygen and nutrients to the body's tissues. Anemic patients feel tired and weak. If red blood cell levels fall too low, a blood transfusion may be given.

Patients receiving chemotherapy are more likely to get infections. This happens because their infection-fighting white blood cells are reduced. It is important to take measures to avoid getting infections. When the white blood cell count drops too low, the doctor may prescribe medications called colony stimulating factors that help white blood cells grow. Neupogen and Leukine are two colony stimulants used as treatments to help fight infection.

Platelets are blood cells that make the blood clot. When patients do not have enough platelets, they may bleed or bruise easily, even from small injuries. Patients with low blood platelets should take precautions to avoid injuries. Medicines such as aspirin and other pain relievers can affect platelets and slow down the clotting process.

Chemotherapy can cause irritation and dryness in the mouth and throat. Painful sores may form that can bleed and become infected. Precautions to avoid this side effect include getting dental care before chemotherapy begins, brushing the teeth and gums regularly with a soft brush, and avoiding mouth washes that contain salt or alcohol.

Normal results

The main goal of chemotherapy is to cure cancer. Many cancers are cured by chemotherapy. It may be used in combination with surgery to keep a cancer from spreading to other parts of the body. Some widespread, fast-growing cancers are more difficult to treat. In these cases, chemotherapy may slow the growth of the cancer cells.

Doctors can tell if the chemotherapy is working by the results of medical tests. Physical examination, blood tests, and x rays are all used to check the effects of treatment on the cancer.

The possible outcomes of chemotherapy are:

• Complete remission or response. The cancer completely disappears. The course of chemotherapy is completed and the patient is tested regularly for a recurrence.
• Partial remission or response. The cancer shrinks in size but does not disappear. The same chemotherapy may be continued or a different combination of drugs may be tried.
• Stabilization. The cancer does not grow or shrink. Other therapy options may be explored. A tumor may stay stabilized for many years.
• Progression. The cancer continues to grow. Other therapy options may be explored.
• A secondary malignancy may develop from the one being treated, and that second cancer may need additional chemotherapy or other treatment.

Resources

PERIODICALS

"Gene Therapy and Chemotherapy Combine to Stop Breast Cancer and its Metastasis." Gene Therapy Weekly October 30, 2003: 2.

"Melatonin Improves the Efficacy of Chemotherapy and Quality of Life." Biotech Week September 10, 2003: 394.

"Obesity May Reduce Efficacy of High-dose Chemotherapy." Health & Medicine Week August 11, 2003: 385.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA 30329-4251. (800) 227-2345. 〈http://www.cancer.org〉.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 422-6237. 〈http://www.nci.nih.gov〉.

KEY TERMS

Adjuvant therapy— Treatment given after surgery or radiation therapy to prevent the cancer from coming back.

Alkaloid— A type of chemical commonly found in plants and often having medicinal properties.

Alykylating drug— A drug that kills cells by directly damaging DNA.

Antiemetic— A medicine that helps control nausea; also called an anti-nausea drug.

Antimetabolite— A drug that interferes with a cell's growth or ability to multiply.

Platelets— Blood cells that function in blood clotting.

Chemotherapy

Definition

Chemotherapy is the treatment of cancer with anticancer drugs.

Purpose

The purpose of chemotherapy is to kill cancer cells. Not only is it often used to treat patients with cancer that has metastasized (spread) from the site in the body where it originated, today chemotherapy can be used to prevent metastasis as well. Chemotherapy destroys cancer cells throughout the body, killing cells that have broken off from the main tumor and traveled through the blood or lymph systems to other parts of the body.

Chemotherapy can cure some types of cancer. In some cases, it is used to slow the growth of cancer cells or to keep the cancer from spreading to other parts of the body. When a cancer has been removed by surgery, chemotherapy may be used to keep the cancer from recurring; this is known as adjuvant therapy. Chemotherapy also can ease the symptoms of cancer, helping some patients to have a better quality of life.

Precautions

There are many different types of chemotherapy drugs. Oncologists (specialists in cancer) determine which drugs are best suited for each patient. This decision is based on the type of cancer, the patient's age, health, and preferences, as well as other drugs the patient is taking. Some patients may not tolerate certain chemotherapy drugs if they have other illnesses such as heart disease, kidney disease, or diabetes.

Chemotherapy, whether administered in the hospital, clinic, or at home, is prepared by the pharmacist. The pharmacy and pharmacy assistants provide and reinforce patient education about common as well as infrequent side effects of chemotherapy. When administered in the hospital, clinic, physician's office, or other treatment setting, it is usually administered by a specially trained nurse, mid-level practitioner (physician assistant of nurse practitioner), or physician.

Description

More than 50 chemotherapy drugs are currently available to treat cancer, and many more are being tested for their ability to destroy cancer cells. Most chemotherapy drugs interfere with the ability of cells to grow or multiply. Although these drugs affect all cells in the body, most useful treatments are more effective against rapidly growing cancer cells. Since chemotherapy affects rapidly growing cells, it often affects cells that normally grow rapidly such as cells in the bone marrow, stomach, intestines, and hair follicles. This is why some of the most common side effects of chemotherapy are bone marrow suppression, nausea, vomiting, and hair loss.

Types of chemotherapy drugs

Chemotherapy drugs are classified based on their mechanisms of action (how they work). The main types of chemotherapy drugs are:

• Alkylating drugs kill cancer cells by directly attacking DNA, the genetic material of the genes. Cyclophosphamide is an example of an alkylating drug.
• Antimetabolites interfere with the production of DNA thereby preventing cells from growing and multiplying. An example of an antimetabolite is 5-fluorouracil (5-FU).
• Antitumor antibiotics are made from natural substances such as fungi in the soil. They interfere with important cell functions, including production of DNA and cell proteins. Doxorubicin and bleomycin belong to this group of chemotherapy drugs.
• Plant alkaloids prevent cells from dividing normally. Vinblastine and vincristine are plant alkaloids obtained from the periwinkle plant.
• Steroid hormones slow the growth of some cancers that depend on hormones. For example, tamoxifen is used to treat breast cancers that depend on the hormone estrogen for growth.

Combination chemotherapy

The oncologist decides which chemotherapy drug or combination of drugs will work best for each patient. The use of two or more drugs together often works better than a single drug alone. This is called combination chemotherapy. Scientific studies and clinical research trials of different drug combinations help determine which combinations are most effective for each type of cancer.

How chemotherapy is administered

Chemotherapy is administered in different ways, depending on the drugs to be given and the type of cancer. The prescribed dose depends on several factors, one of which is the patient's body weight.

Chemotherapy may be administered by one or more of the following methods:

• orally
• intramuscular (IM) or subcutaneous injection
• through a catheter or port
• topically

Oral chemotherapy, given by mouth, may be in the form of a pill, capsule, or liquid. This is the easiest method of administration and can usually be done at home.

Intravenous (IV) chemotherapy is injected into a vein. A small needle is inserted into a vein on the hand or lower arm. The needle is usually attached to a small tube called a catheter, which delivers the drug to the needle from an IV bag or bottle.

Intramuscular (IM) chemotherapy is injected into a muscle. Chemotherapy given by intramuscular injection is absorbed into the blood more slowly than IV chemotherapy. Because of this, the effects of IM chemotherapy may last longer than chemotherapy given intravenously. Chemotherapy may also be injected subcutaneously (under the skin). Injection of chemotherapy directly into the cancer is called intralesional injection.

Chemotherapy may also be given by a catheter or port permanently inserted into a central vein or body cavity. A port is a small reservoir or container that is placed in a vein or under the skin in the area where the drug will be administered. These methods eliminate the need for repeated injections and may allow patients to spend less time in the hospital while receiving chemotherapy. A common location for a permanent catheter is the external jugular vein in the neck. Intraperitoneal (IP) chemotherapy is administered into the abdominal cavity through a catheter or port. Chemotherapy administered by catheter or port into the spinal fluid surrounding the brain or spine is called intrathecal (IT) administration. Catheters and ports may also be placed in the chest cavity, bladder, or pelvis, depending on the location of the cancer to be treated.

Topical chemotherapy is given as a cream or ointment applied directly to the cancer. It may be used to treat certain types of skin cancer.

Treatment location and schedule

Patients may take chemotherapy at home, in the physician's office, or as an inpatient or outpatient at the hospital. Many patients stay in the hospital when first beginning chemotherapy, so they can be observed and monitored for any side effects.

The frequency and duration of chemotherapy given depends on the type of cancer, the patient response to the drugs, patients' overall health and ability to tolerate the drugs, and on the types of drugs used. Chemotherapy administration may take only a few minutes or may last as long as several hours. Chemotherapy may be given daily, weekly, or monthly. A rest period may follow a course of treatment before the next course begins. In combination chemotherapy, more than one drug may be given at the same time, or they may be given alternately, one following the other.

Preparation

A number of medical tests are performed before chemotherapy is started. The oncologist will determine the extent to which the cancer has spread from the results of x rays and other imaging tests and from biopsies. Radiologic technologists and technicians perform imaging studies. Analysis of the biopsy will be performed by a pathologist, assisted by laboratory technicians.

Blood tests, drawn by laboratory technicians or nurses, provide important information about the function of the blood cells and levels of chemicals in the blood. A complete blood count (CBC) is commonly performed before and on a regular basis during treatment. The CBC shows the numbers of white blood cells, red blood cells, and platelets in the blood. Because chemotherapy affects the bone marrow, where blood cells are made, levels of these cells often drop during chemotherapy. The white blood cells and platelets are most likely to be affected by chemotherapy. A drop in the white blood cell count means that the immune system may not function properly and the patient may become prone to infection. Low levels of platelets may cause a patient to bleed from minimal trauma or even spontaneously with no trauma. A low red blood cell count can lead to anemia (deficiency of red blood cells) and fatigue.

Sometimes, patients taking chemotherapy drugs known to cause nausea are given antiemetics before chemotherapy is administered to lessen feelings of nausea. Two anti-nausea medications that may be used are Kytril and Zofran.

Patients may also be advised to prepare for chemotherapy and reduce nausea by eating and drinking normally until about two hours before a chemotherapy session. They should eat high carbohydrate, low-fat foods and avoid spicy foods.

Aftercare

Patient education about how to control side effects after chemotherapy includes:

• Encouraging patients to adhere to instructions given by their health care team.
• Reinforcing correct use of all prescribed medications.
• Advising patients to eat small amounts of bland foods and drink lots of fluids.
• Instructing patients to get plenty of rest.

Some patients find that breathing fresh air or mild exercise, such as walking, helps to relieve the stress and side effects associated with chemotherapy.

Complications

Chemotherapy drugs are toxic to normal cells as well as cancer cells. Doses that will destroy cancer cells will likely cause damage to some normal cells. Physicians adjust (titrate) doses to do the least amount of harm possible to normal cells. Some patients feel few or no side effects, and others may experience more serious side effects. In some cases, a dose adjustment is all that is needed to reduce or stop a side effect.

Some chemotherapy drugs have more side effects than others. The most common side effects include:

• nausea and vomiting
• loss of appetite
• hair loss (alopecia)
• anemia and fatigue
• infection
• easy bleeding or bruising
• sores in the mouth and throat
• neuropathy and other damage to the nervous system
• kidney damage

Nausea and vomiting are common, but can usually be controlled by taking antinausea drugs, drinking enough fluids, and avoiding spicy foods. Loss of appetite may be due to nausea or the stress of undergoing cancer treatment. Also, although some chemotherapy drugs cause alopecia, it is almost always temporary and reversible.

Low blood cell counts caused by the effect of chemotherapy on the bone marrow can lead to anemia, infections, and easy bleeding and bruising. Patients with anemia have too few red blood cells to deliver oxygen and nutrients to the body's tissues. Anemic patients feel tired and weak. If red blood cell levels fall too low, a blood transfusion may be given.

Patients receiving chemotherapy are more likely to get infections because white blood cells are reduced. It is important to take measures to avoid infections. When the white blood cell count drops too low, the physician may prescribe medications called colonystimulating factors that help white blood cells grow. Neupogen and Leukine are two colony stimulants used as treatments to help fight infection.

Platelets are blood particles that make the blood clot. When patients do not have enough platelets, they may bleed or bruise easily, even from small injuries. Patients with low blood platelets should be advised to take precautions to avoid injuries. Medicines such as aspirin and other pain relievers can impair platelet function and slow the clotting process.

Chemotherapy can cause irritation and dryness in the mouth and throat. Painful sores may form that can bleed and become infected. Patients should be advised about actions they might take to prevent or reduce mouth irritation. Precautions to avoid this side effect include dental care before chemotherapy begins, brushing the teeth and gums regularly with a soft brush, and avoiding mouthwashes that contain salt or alcohol.

Results

The primary goal of chemotherapy is to cure cancer. Some cancers, such as Hodgkin's disease and acute lymphocytic leukemia, may be cured by chemotherapy. Used as adjuvant therapy, in combination with surgery, it may prevent a cancer from spreading to other parts of the body. Some widespread, fastgrowing cancers are more difficult to treat. In these cases, chemotherapy may slow the growth of the cancer cells.

Physicians determine the extent to which chemotherapy is effective by closely monitoring the results of medical tests. Physical examination, blood tests, and imaging studies are used to monitor and assess the effects of treatment on the cancer.

The outcomes of chemotherapy include:

• Complete remission or complete response. The cancer completely disappears. The course of chemotherapy is completed, and the patient is tested regularly for a recurrence.
• Partial remission or partial response. The cancer shrinks in size but does not disappear. The same course of chemotherapy may be continued, or a different combination of drugs may be tried.
• Stabilization. The cancer does not grow or shrink. Other therapy options may be explored. A tumor may remain stabilized for many years.
• Progression. The cancer continues to grow. Other therapy options may be explored.
• A new type of malignancy may develop, and this secondary cancer may require additional chemotherapy or other treatment.

Health care team roles

Patients with cancer are usually cared for by a multidisciplinary team of health professionals. The patient's family physician or primary care physician collaborates with other specialists, such as surgeons and oncologists. Radiologic technicians perform imaging studies, and nurses and laboratory technicians may obtain samples of blood, urine, and other laboratory tests.

Before and after chemotherapy, nurses explain the goals and effects of drug treatment and help to prepare patients and families. Depending on the treatment plan, cancer patients may also benefit from rehabilitation therapy with physical therapists, nutritional counseling from dieticians, and counseling from social workers or other mental health professionals.

KEY TERMS

Adjuvant therapy— Treatment given after surgery or radiation therapy to prevent the cancer from coming back.

Alkaloid— A type of chemical commonly found in plants and often having medicinal properties.

Alkylating drug— A drug that kills cells by directly damaging DNA.

Antiemetic— A medicine that helps control nausea; also called an anti-nausea drug.

Antimetabolite— A drug that interferes with a cell's growth or ability to multiply.

Platelets— Blood cells that function in blood clotting.

Resources

BOOKS

Dollinger, Malin, Ernest H. Rosenbaum, and Greg Cable. Everyone's Guide to Cancer Therapy. Kansas City, MO: Andrews McMeel Publishing, 1998.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, GA 30329. (800) ACS-2345.

Cancer Information Service of the National Cancer Institute. (800) 4-CANCER.

OTHER

"Chemotherapy and You: A Guide to Self-Help During Treatment." National Cancer Institute. National Institutes of Health. 〈http://www.cancernet.nci.nih.gov/chemotherapy/chemoint.html〉.

"Introduction to Chemotherapy." OncoLink, University of Pennsylvania Cancer Center. 1998. 〈http://www.oncolink.upenn.edu/specialty/chemo/general/chemo_intro.htm.l〉.