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What is Chemotherapy

 

 

WHAT IS CHEMOTHERAPY?

The thought of chemotherapy frightens many people. Understanding what to expect before, during, and after chemotherapy can calm many of these fears. This essay will help explain what chemotherapy is, how it works, and what to expect, in general, with chemotherapy.

To doctors, nurses, pharmacists, and health professionals, the word chemotherapy means any drug (like aspirin or penicillin) used for treating people with any disease. Cancer chemotherapy is understood to mean medications or drugs that destroy cancer cells. Most lay people, however, think of anti-cancer drugs when they hear the term "chemotherapy." Two of the medical terms often used to describe cancer chemotherapy are antineoplastic (anti-cancer) and cytotoxic (cell-killing).

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

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

There are now well over 90 drugs used for chemotherapy and many more are expected to become available soon. These chemotherapy drugs vary widely in their chemical composition, how they are taken, their usefulness in treating specific forms of cancer, and their side effects. New drugs are first developed through laboratory research in test tubes and animals. Then, their safety and effectiveness are tested in three phases of clinical trials in humans.

Clinical trials are studies of new or experimental drugs (or other new treatments). The study is done when there is a reason to believe a new drug or a new combination of drugs may be of value in curing or controlling cancer. The study will be fully explained to the individual and their family and the individual has the opportunity to volunteer or refuse to participate in the study. Taking part in a clinical trial does not prevent anyone from receiving other medical or nursing care that is needed. Patients who participate in clinical trials make an important contribution to medical care because the study results will also help future patients. And, the participant will be the first to benefit from these new treatments. To learn more about clinical trials, you can contact the American Cancer Society (1-800-ACS-2345 or www.cancer.org) or the National Cancer Institute (1-800-4-CANCER or cancertrials.nci.nih.gov). The National Cancer Institute can provide a listing of clinical trials for people with various types and stages of cancer.

HOW CHEMOTHERAPY WORKS

To understand how chemotherapy works as a treatment it is helpful to understand the normal life cycle of a cell in the body. All living tissue is composed of cells and sustained by cell growth and reproduction that replaces cells lost during injury or normal "wear and tear." The cell cycle is a series of steps through which both normal cells and abnormal cancer cells grow and reproduce to form two new cells. There are 5 steps, called cell cycle phases, that are designated by letters and numbers:

G0, G1, S, G2, and M.

G0, G1, S, G2, and M.

The Cell Cycle
GO = Resting stage
G1 = RNA and protein synthesis
S = DNA synthesis
G2 = Construction of mitotic apparatus
M = Mitosis

Cells in the G0 phase, which is sometimes referred to as the resting phase, have not yet started reproducing. The length of the G0 phase varies from hours to years for different types of cells. When the cell is stimulated to reproduce (for instance, when other cells wear out and need to be replaced), it moves into the G1 phase. During this step, the cell's production of RNA and proteins increase. This phase lasts about 18-30 hours, and is followed by the S phase. During the S phase, the cell replicates its DNA so that both of the new cells it will eventually form will have the right amount of DNA. This phase lasts about 18-20 hours. G2, the period right before the cell starts the process of splitting into two cells, lasts from 2-10 hours. It is also a period when RNA and proteins are formed. The last step is called M for mitosis. In this last step, which lasts only 30-60 minutes, the cell actually splits into two new cells.

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

Although chemotherapy drugs attack reproducing cells, they do not distinguish between reproducing cells of normal tissues (that are replacing worn-out normal cells) and cancer cells. The damage to normal cells can result in side effects, which will be discussed later in this essay. Thus, each time chemotherapy is given it involves a balance between destroying the cancer cells (in order to cure or control the disease) and sparing the normal cells (to minimize undesirable side effects).

GOALS OF TREATMENT WITH CHEMOTHERAPY

There are three main goals of chemotherapy treatment. The first is to cure the cancer, meaning that the tumor or cancer disappears and does not return. If this is not possible, the second goal is to control the disease (stop the cancer from growing and spreading) in order to provide the best quality of life for the person with cancer. Sometimes cure and control are not possible if the cancer is in an advanced stage. At this point the goal is called palliation. This means that chemotherapy drugs will be used to relieve symptoms caused by the cancer, thereby improving the patientís quality of life, even though the length of their life may not be prolonged.

For some patients, chemotherapy is the only treatment used in an attempt to cure, control, or palliate their cancer. In other cases, chemotherapy may be given as neoadjuvant therapy before surgery or radiation, or as adjuvant therapy after surgery or radiation. Adjuvant chemotherapy is given to prevent the reproduction of stray cancer cells remaining in the body after surgery or radiation. In most cases, these stray cancer cells cannot be recognized by routine tests such as x-rays, but are assumed to be present. Neoadjuvant chemotherapy may be used to shrink a large tumor so that it can be removed by surgery or a less extensive operation can be used to accomplish that goal.

TYPES OF CHEMOTHERAPY DRUGS

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

Alkylating agents work directly on DNA to prevent the cancer cell from reproducing. As a class of drugs, these agents are not phase-specific (they work in all phases of the cell cycle). These drugs are active against chronic leukemias, non-Hodgkinís lymphoma, Hodgkin's disease, multiple myeloma, and certain cancers of the lung, breast, and ovary. Examples of alkylating agents include busulfan, cisplatin, cyclophosphamide (cytoxan), dacarbazine, ifosfamide, mechlorethamine (mustargen), and melphalan.

Nitrosureas act in a similar way to alkylating agents. They inhibit enzymes that are needed for DNA repair. These agents are able to travel to the brain so they are used to treat brain tumors, as well as non-Hodgkin's lymphomas, multiple myeloma, and malignant melanoma. Examples of nitrosureas include carmustine and lomustine.

Antimetabolites are a class of drugs that interfere with DNA and ribonucleic acid (RNA) growth. These agents are phase specific (S phase) and are used to treat chronic leukemias as well as tumors of breast, ovary and the gastrointestinal tract. Examples of antimetabolites include 5-fluorouracil, methotrexate, gemcitabine, cytarabine (Ara-C), and fludarabine.

Antitumor antibiotics have both antimicrobial and cytotoxic activity. These drugs also interfere with DNA by chemically inhibiting enzymes and mitosis or altering cellular membranes. These agents are not phase specific so they work in all phases of the cell cycle. Thus, they are widely used for a variety of cancers. Examples of antitumor antibiotics include bleomycin, dactinomycin, daunorubicin, doxorubicin (Adriamycin), and idarubicin.

Mitotic inhibitors are plant alkaloids and natural products that can inhibit mitosis or inhibit enzymes that prevent protein synthesis needed for reproduction of the cell. These are phase cycle specific and work during the M phase. Examples of mitotic inhibitors include paclitaxel, docetaxel, etoposide, vinblastine, vincristine, and vinorelbine.

Other chemotherapy drugs which have slightly different mechanisms of action and do not fit into any of the above categories include such drugs as L-asparaginase, amsacrine, and tretinoin.

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

Sex hormones or hormone-like drugs alter the action or production of female or male hormones and are used to slow the growth of breast, prostate, and endometrial (lining of the uterus) cancer. Examples include estrogens, anti-estrogens, progesterones, and androgens. Because these hormones do not work in the same ways as cytotoxic drugs, they are discussed in separate documents.

Immunotherapy drugs given to people with cancer are intended to stimulate their immune systems to more effectively recognize and attack cancer cells. These drugs are a unique area of chemotherapy and are covered in a separate document.

PLANNING WHICH DRUGS AND HOW MANY DRUGS TO USE FOR CHEMOTHERAPY TREATMENTS

The most important factors in choosing which drugs to use for each patient's chemotherapy treatment are the type of cancer and its stage (how far it has spread). The patient's age, general state of health, other serious health problems (such as liver or kidney diseases), and other types of anticancer treatments given in the past are also taken into account. The oncologist will consider these factors in the context of information published in medical journals and textbooks describing the outcomes of similar patients treated with various chemotherapy drugs. In some cases, the best choice of chemotherapy drugs, doses, and schedules for giving each drug are relatively clear, and most oncologists would recommend the same treatment. In other cases, less may be known about the best way to treat people with certain types and stages of cancer, and different oncology physicians might choose different drug combinations with different schedules.

Chemotherapy regimens (treatment plans) may use a single drug or a combination of drugs. Oncologists recommend a combination of drugs for most people with cancer. Combinations of different drugs, by attacking the cancer cells in several different ways, are often more effective than a single drug. And different drugs may have different side effects, so it is often better to use moderate doses that cause bearable side effects rather than very high doses of a single drug that might cause severe side effects and possibly permanent damage to an important organ. However, there are important exceptions to this rule, and a single chemotherapy drug may be the best option for some people with certain types of cancer.

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

PLANNING DRUG DOSES AND SCHEDULES

Some drugs, especially those available to people without a prescription have a relatively wide therapeutic index. This means that wide ranges of doses can be used effectively and safely. For example, the label on a bottle of aspirin may suggest taking two tablets for a mild headache. But, one tablet will probably help many people with a mild headache, and taking three tablets will not cause serious harm to most people. Most chemotherapy drugs, on the other hand have a narrow range of safe and effective doses. Not taking enough will not effectively treat the cancer and taking too much may cause life-threatening side effects. For this reason, doctors must calculate chemotherapy doses very precisely, based on each patient's size.

The chemotherapy doses, usually measured in milligrams (mg), given to people with cancer are sometimes based on their body weight in kilograms (1 kilogram is 2.2 pounds). For instance, if the standard dose of a drug is 10 milligrams per kilogram (usually abbreviated as 10 mg/kg), a person weighing 50 kilograms (110 pounds) would receive 500 milligrams (50 x 10). Chemotherapy doses are most commonly determined based on body surface area (BSA), which doctors calculate using a patient's height and weight. Dosages for children and adults differ, even after BSA is taken into account. Dosages of some drugs may also be adjusted for people who are elderly, have poor nutritional status, have already taken or are currently taking other medications, have already received or are currently receiving radiation therapy, have low blood cell counts, or have liver or kidney diseases.

Chemotherapy is generally given at regular intervals called cycles. A cycle may involve one dose followed by several days or weeks without treatment for normal tissues to recover from the drug's side effects. Doses may be given several days in a row, or every other day for several days, followed by a period of rest. If more than one drug is used, the treatment plan will specify how often and exactly when each drug should be given. The number of cycles a person receives may be determined before treatment starts (based on the type and stage of cancer) or may be flexible, in order to take into account how quickly the tumor is shrinking. Certain serious side effects may also require doctors to adjust chemotherapy plans to allow the patient time to recover.

WHERE CAN PEOPLE RECEIVE CHEMOTHERAPY TREATMENTS?

Chemotherapy treatments may be given in:

  • a hospital
  • a doctorís office
  • an outpatient clinic
  • an individualís home
  • a workplace

In addition to convenience, how the drugs are given is important in considering the best place to receive chemotherapy. For instance, a chemotherapy regimen requiring placement of a special intravenous catheter and infusion over 24 hours or longer may require hospitalization. And, the specific drugs and their doses, as well as the patient's general state of health, will determine the expected side effects and whether the patient needs to be monitored more closely during treatment.

WAYS TO TAKE CHEMOTHERAPY

Drugs used in chemotherapy regimens can be given in many ways. They may be given orally (by mouth), topically (on top of the skin as a cream or lotion), intravenously (into a vein or IV), intramuscularly (into a muscle or IM), subcutaneously (under the skin or SQ), intra-arterially (into an artery), intrathecally (into the central nervous system via the cerebrospinal fluid), intrapleurally (into the chest cavity), intraperitoneally (into the abdominal cavity), intravesically (into the bladder), and intralesionally (into the tumor).

Oral Versus Parenteral Chemotherapy

Some chemotherapy drugs are never taken by mouth because the digestive system cannot absorb them or because they are very irritating to the digestive system. Even when a drug is available in an oral form, this method may not be the best choice for some people who already have certain digestive system symptoms (vomiting, diarrhea, or severe nausea), cannot swallow liquids or pills, or cannot remember when or how many pills to take.

The term parenteral is used to describe drugs given intravenously, intramuscularly, or subcutaneously. The intravenous route is most common. Intramuscular and subcutaneous injections are less frequently used because many drugs can be very irritating or even damaging to the skin or muscle tissue. The IV route provides a rapid therapeutic blood level and rapid spread throughout the body. IV therapy may be given by several methods. These include peripheral access (through a vein in the arm or hand), or through a vascular access device (VAD), which is a device with a catheter implanted into a larger vein in the chest, neck, or arm. There are different types of VADs with different types of catheters and implantable ports. VADs are used if there is a need:

  • to give several drugs at one time
  • for long-term therapy
  • for continuous infusion chemotherapy
  • to give drugs that are vesicants that can cause serious damage to skin and muscle tissue if they leak outside of a vein. (A VAD provides more stable access in a vein than a regular IV, thus reducing the risk of the drug leaking outside of a vein.)

The type of VAD used is based on the length of chemotherapy planned, patient and doctor preference, care required to maintain the VAD and cost.

Types of Vascular Access Devices

Type of Device Comments
PICC (peripherally inserted central catheter) Allows for continuous access to peripheral vein for several weeks. No surgery needed.
Care of catheter needed.
Midline catheter (Per-Q-Cath Midline, Groshong Midline) Catheter is not inserted as far as a PICC. Used for intermediate length therapy when a regular peripheral IV is not advisable or available.
(TCVC) Tunneled Central Venous Catheter Catheter with multiple lumens surgically placed in large central vein and catheter tunneled under the skin. Care of catheter needed.
Implantable Venous Access Port (Port-A-Cath, BardPort, PassPort, Medi-port) A port of plastic, stainless steel, or titanium with a silicone septum with catheter surgically placed under the skin of the chest or arm in a large or central vein. The port is accessed by a needle to give chemotherapy.
Implantable pump A titanium pump with an internal power source surgically implanted to give continuous infusion chemotherapy, usually at home. There is a refillable reservoir for continuous infusions.

Regional Chemotherapy

When there is a need to give high doses of chemotherapy to a specific area of the body, it may be given by a regional method. Regional chemotherapy involves directing the anticancer drugs into the tumor-bearing region of the body. The purpose is to achieve greater regional exposure than could be achieved by systemic chemotherapy while minimizing side effects to other parts of the body. Examples of regional chemotherapy include intra-arterial, intravesical, intrathecal, intrapleural, and intraperitoneal routes.

Intra-arterial infusions gained some popularity during the 1980s. An intra-arterial infusion allows a chemotherapy drug to be given directly through a catheter in an artery to an organ (like the liver or brain) or to an extremity such as the leg. The catheter is attached to an implanted or portable pump. Although this approach sounds like a good idea for increasing effectiveness and reducing side effects, most studies have not found it to be as useful as it was anticipated. Although clinical trials continue to refine this approach to chemotherapy, it is not widely used except in these studies.

Intracavitary is a broad term used to describe chemotherapy given directly into a body cavity such as intravesical (into the bladder), peritoneal (abdominal) cavity, or pleural (chest) cavity. The drug is given through a catheter placed directly into one of these areas. Intravesical chemotherapy is especially effective for early stage bladder cancer. The chemotherapy is usually given weekly for 4 to 12 weeks. Each treatment involves the placement of a urinary catheter to give the drug into the bladder. The drug is retained in the bladder for 2 hours and then drained. The urinary catheter is removed after each treatment. Intrapleural and intraperitoneal chemotherapy are not used very often, but are useful for some people with mesothelioma (cancer that develops in the lung pleura), ovarian cancer that has spread to the peritoneum, and lung or breast cancers that have spread to the pleura. Intrapleural chemotherapy is given through large or small chest catheters that may be connected to an implantable port. These catheters can be used to administer drugs as well as to drain fluid that often accumulates in the pleural or peritoneal cavity when cancer has spread to these tissues. Intraperitoneal chemotherapy is given through a Tenkhoff catheter (a catheter specially designed for removing or adding large amounts of fluid from or into the peritoneum) or through an implanted port. Cancers of the appendix that spread extensively within the abdomen are sometimes treated with intraperitoneal chemotherapy.

Most chemotherapy drugs that are given into veins are unable to cross the barrier between the bloodstream and the central nervous system (brain and spinal cord) called the blood-brain barrier. Intrathecal chemotherapy is given directly into the cerebrospinal fluid (fluid that surrounds the brain and spinal cord), and can reach cancer cells in the central nervous system. Intrathecal chemotherapy may use one of two methods. In one method, the chemotherapy is given by a lumbar puncture (spinal tap) daily or weekly into the space around the spinal cord. The second method uses a special reservoir called an Ommaya reservoir, which is placed into the skull and has a catheter inserted into a ventricle (a space inside the brain filled with cerebrospinal fluid). Intrathecal chemotherapy may be necessary for some people with leukemia or other cancers that have spread to the brain or spinal cord.

Safety Precautions for Healthcare Professionals

Many chemotherapy drugs are mutagenic (can cause abnormal changes in DNA), teratogenic (may be able to alter development of a fetus or embryo, leading to birth defects), or carcinogenic (able to cause another type of cancer). Some may cause localized skin irritation or damage. Therefore, the nurses and doctors who give chemotherapy will take precautions to avoid direct contact with the drugs.

Nurses may wear special gloves and gowns when preparing and giving the chemotherapy drugs. Additionally, the drug will be prepared by pharmacists or nurses in areas with special ventilation systems. If patients are hospitalized, nurses and health care professionals may take special precautions in handling urine and stool for two days after treatment. Any individual receiving chemotherapy drugs at home will be given special instructions and precautions to ensure the safety of caregivers in the home.

Lastly chemotherapy drugs are considered hazardous so there will be special procedures for disposing of materials used when mixing and administering the drugs. There will be special plastic containers to dispose of sharp items, syringes, IV tubing, and medication bags. Gowns and gloves will be disposed of in special bags. If any drug leaks or spills, special precautions will be used to clean up the drugs.

SIDE EFFECTS OF CHEMOTHERAPY

Although chemotherapy is given to kill cancer cells, it also can damage normal cells. Normal cells that are rapidly dividing, such as blood cells, cells of hair follicles, and cells in the reproductive and digestive tracts are more likely to be damaged by chemotherapy medications. Damage to these cells account for many of the side effects of chemotherapy drugs.

Bone Marrow Suppression

The bone marrow is the tissue inside some bones that produces white blood cells (WBCs), red blood cells (RBCs), and blood platelets. Damage to the blood cell-producing tissues of the bone marrow is called bone marrow suppression , or myelosuppression, and is one of the most common side effects of chemotherapy. Cells produced in the bone marrow tissue are growing rapidly and are sensitive to the effects of chemotherapy. Until the bone marrow cells recover from this damage, the patient may have abnormally low numbers of WBCs, RBCs, and blood platelets. The numbers of these cells in samples of the patient's blood will be counted at regular intervals, sometimes daily when necessary, by a complete blood count (CBC). Bone marrow samples may also be taken periodically to check on the blood-forming marrow cells that develop into WBCs, RBCs, and blood platelets.

The decrease in blood cell counts does not occur immediately after chemotherapy because the drugs do not destroy the cells already in the blood stream. Instead the drugs temporarily prevent formation of new blood cells by the bone marrow. It is important to understand that each type of blood cell has a different life span. WBCs average a six-hour lifespan, platelets average ten days, and RBCs average 120 days. As blood cells normally wear out, they are constantly replaced by the bone marrow. Following chemotherapy, as these cells wear out, they are not replaced as they would be normally and the blood cell levels will begin to drop. The type and dose of the chemotherapy will influence how low the blood cell counts will drop and how long it will take for the drop to occur.

The lowest count that blood cell levels fall to is called the nadir. The nadir for each blood cell type will occur at different times but usually, WBCs and platelets will reach their nadir within 7-14 days. RBCs live longer and will not reach a nadir for several weeks.

Knowing what the three types of blood cells normally do can help in understanding the effects of low blood cell counts. WBCs help the body resist infections. Platelets help prevent excessive bleeding by forming plugs to seal up damaged blood vessels. RBCs bring oxygen to tissues so cells throughout the body can use that oxygen to turn certain nutrients into energy. The side effects caused by low blood cell counts will be at their maximum peak when the WBC, blood platelet, and RBC are at their nadirs or lowest value.

Low white blood cell counts: The medical term for low WBC count is leukopenia. Blood normally has between 4,000 and 10,000 WBCs per cubic millimeter. The major function of WBCs is to defend the body against infections. WBCs are divided into 2 main categories: 1) granulocytes, which contain granules in the cytoplasm of the cell, include 3 sub-types of WBCs - neutrophils, eosinophils and basophils 2) agranulocytes, which do not contain granules in the cystoplasm of the cell, include 3 sub-types of WBCs - lymphocytes, monocytes and macrophages.

Granulocytes, especially neutrophils, provide an important defense against infections. They also are the most numerous type of WBC. Neutropenia, an abnormally low actual decrease in neutrophils, is the most common factor that makes individuals with cancer at risk for infection. The normal range of neutrophils is between 2500 and 6000 cells per cubic millimeter. To determine how likely an individual is to develop an infection, health care providers calculate a number called the absolute neutrophil count (ANC). When an individual has an ANC of 1000 or less they are considered to be neutropenic and at risk to develop an infection. An ANC < 500 is considered severe neutropenia.

Even though the WBC count or the neutrophil count is low, it does not mean every individual will have an infection. Signs and symptoms of an infection are:

  • fever
  • sore throat
  • new cough or shortness of breath
  • nasal congestion
  • burning during urination
  • shaking chills
  • redness, swelling and warmth at the site of an injury

Fever is a very important sign and may be the first sign of an infection. Usually individuals are instructed to call their doctor or nurse with a fever greater than or equal to 100.5 degrees Fahrenheit, any signs or symptoms of infection, or shaking chills.

Patients are given preventive care measures to reduce their risk of infection and exposure to others with infections. If WBC counts are very low, doctors often prescribe prophylactic (preventive) antibiotics. These anti-infection drugs may be given intravenously or by mouth. (For specific care measures, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

There are several naturally occurring hematopoietic growth factors that stimulate the production of various types of blood cells. These growth factors are also called colony-stimulating factors. Scientists have recently learned how to produce these growth factors in the laboratory so they are now available as drugs. The two growth factors that stimulate production of WBCs are granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim, Leukine) and granulocyte colony stimulating factor (G-CSF, filgrastim, Neupogen). These drugs are often given to people the day after they receive myelosuppressive chemotherapy for up to two weeks. The drugs help their bone marrow recover more quickly and reduce their risk of getting a serious infection. Because of the serious risk of infections, additional chemotherapy doses may be delayed when a patient has a very low white blood cell counts. In some situations, doctors may prescribe growth factors in order to prevent the WBC from falling too low, so that chemotherapy can be given on schedule. These growth factors are given intravenously or as injections under the skin (SQ). The injections are given by nurses, when the patient is in the hospital, but patients or their family members learn how to give these injections at home.

Low red blood cell counts: Not having enough red blood cells is called anemia. Blood normally has between 4.0 and 6.0 million RBCs per cubic millimeter. Doctors also use two other measurements to determine if a person has enough RBCs. The first of these, called the hematocrit, is the percentage of total blood volume occupied by RBCs and its normal range is between 36 and 42%. The red pigment in RBCs that carries oxygen is hemoglobin. If there are not enough RBCs, the blood hemoglobin concentration will be less than its usual range of 12 to 16 grams per deciliter (g/dL). People with anemia may have the following symptoms:

  • fatigue
  • dizziness
  • headaches
  • irritability
  • shortness of breath
  • an increase in heart rate and/or rate of breathing

Anemia due to chemotherapy is temporary. But, blood transfusions may be needed for a period of time until the bone marrow is healthy enough to replace worn-out RBCs. Bleeding caused by surgery or the tumors (a common occurrence with colorectal cancers, for example) will make anemia even worse. Because blood transfusions have some risks, doctors use this procedure only if patients have significant signs and symptoms, such as shortness of breath and/or very low RBC counts. Other factors will also affect this decision. For example, people with heart or lung diseases are more sensitive to anemia. A newer option for treating anemia caused by chemotherapy is erythropoeitin (EPO, Procrit). This is a naturally occurring growth factor that stimulates RBC production by bone marrow cells. These drugs can relieve symptoms of anemia and reduce the need for blood transfusions. Erythropoietin is generally given three times per week by injection under the skin (SQ) until the hematocrit increases to 36% to 40%.

Low platelet counts: The normal range for platelet counts is between 150,000 and 450,000 per cubic millimeter. The medical term for a low platelet count is thrombocytopenia. People with low platelet counts will tend to:

  • bruise easily
  • bleed longer than usual after minor cuts or scrapes
  • have bleeding gums or nose bleeds
  • develop ecchymoses (large bruises) and petechiae (multiple small bruises)
  • have serious internal bleeding if the platelet count is very low

Although low platelet counts resulting from chemotherapy are temporary, they can cause serious blood loss from injury or bleeding that can damage internal organs. (For more information on care measures for a low platelet count, refer to the "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Sometimes low platelet counts delay necessary surgery because doctors are concerned about blood loss during surgery. If platelet counts are very low (below 10,000) or if a person with moderately low counts has greater than normal bleeding or bruising, platelet transfusions may be given. Transfused platelets last only a few days, and some people who have received multiple platelet transfusions can develop an immune reaction that destroys donor platelets. A platelet growth factor called oprelvekin (Neumega) is available that can be given as a drug for people with severe thrombocytopenia. This decreases their need for platelet transfusions and can stop increased bleeding. It is given under the skin (SQ) in daily doses.

Hematopoietic stem cell transplantation: Hematopoietic stem cell transplantation (HSCT) is the term now used to include bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). These therapies permit the use of especially high doses of chemotherapy and/or total body irradiation (TBI) to kill the cancer cells. In the process of killing the cancer cells, hematopoietic (blood forming) stem cells of the patientís normal bone marrow are also killed. Stem cells removed from the patient before chemotherapy or stem cells from a donor are used to replace these cells.

Hair Loss

The rapidly growing cells of hair follicles are affected by chemotherapy, producing hair that is brittle and breaks off at the surface of the scalp or is spontaneously released from the follicle. Not all individuals receiving chemotherapy will lose their hair. Hair loss depends on which drugs are given, their doses, and the length of treatment. Individuals may experience thinning of hair or complete loss. Usually this occurs 2 to 3 weeks after treatment begins. Loss of eyebrows, eyelashes, pubic, and trunk hair is usually less severe as the growth is less active in these hair follicles than in the scalp.

Alopecia (hair loss) due to chemotherapy is almost always temporary rather than permanent. Unlike some other side effects of chemotherapy, hair loss is never life-threatening. But it may have a substantial impact on a personís quality of life. Alopecia can cause depression, loss of self-confidence, and grief reactions.

Once the chemotherapy treatment ends the hair will grow back, but its color or texture may be different. Hair will start to grow again three to four months after hair loss has occurred (For information on care measures refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Appetite Loss and Weight Loss

Anorexia is a decrease or loss of appetite. Most chemotherapy medications can cause some degree of anorexia. Anorexia may be mild, or it may lead to cachexia, a form of malnutrition. Loss of appetite, as well as weight loss, may result directly from effects of the cancer on the bodyís metabolism.

Proper nutrition helps strengthen the body to fight the disease and cope with cancer treatments. Decreased appetite is generally temporary and returns when chemotherapy is finished. It may take several weeks after chemotherapy is finished for the appetite to recover. With some chemotherapy, loss of appetite may be more severe. Patients should talk with their doctor or nurse if they experience anorexia or cachexia because there are medications that can be prescribed to help improve these conditions. (For information on specific care measures for loss of appetite, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Taste Changes

Cancer treatments and the cancer itself can alter the taste sensations of people with cancer. Taste changes can contribute to anorexia and malnutrition. Patients experiencing taste changes due to chemotherapy may notice:

  • they either dislike or have an increased desire for sweet foods
  • they dislike bitter tastes
  • they dislike tomatoes and tomato products
  • they dislike beef or pork
  • a constant metallic or medicinal taste sensation

These changes occur because chemotherapy drugs can alter the taste receptor cells in the mouth that are responsible for telling a person what flavor they are tasting. Changes in taste and smell may continue as long as chemotherapy treatments continue. Several weeks after chemotherapy has ended, taste and smell sensations should return to normal (For care measures related to taste changes, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Stomatitis and Esophagitis

Stomatitis is the inflammation and sores within the mouth that may result from chemotherapy. Similar changes in the throat or the esophagus (the tube that leads from the throat to the stomach) are called pharyngitis and esophagitis. The term mucositis is used to refer to inflammation of the lining layer of the mouth, throat, and esophagus. The first signs of mouth sores occur when the lining of the mouth appears pale and dry. Later, the mouth, gums, and throat feel sore and become red and inflamed. The tongue may "be coated" and swollen, leading to difficulty swallowing, eating, and talking. Stomatitis, pharyngitis, and esophagitis can lead to bleeding, painful ulceration, and infection. Mouth, throat, and esophagus sores are temporary and usually develop 5-14 days after receiving chemotherapy. Fortunately, they are temporary and will heal completely once chemotherapy is finished (For oral self-care measures to prevent or minimize stomatitis and esophagitis, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Nausea and Vomiting

Although there are new medications to both prevent and treat nausea and vomiting, it is a possible side effect of chemotherapy. Chemotherapy agents cause nausea and vomiting for a variety of reasons. They irritate the lining of the stomach and duodenum. This stimulates certain nerves that lead to the vomiting center in the brain. Nausea is an unpleasant wavelike sensation in the stomach and back of throat. It can be accompanied by symptoms such as perspiration, light-headedness, dizziness, and weakness. It can lead to retching and/or vomiting. Retching is a rhythmic movement of the diaphragm and stomach muscles that are controlled by the vomiting center. Vomiting is a process controlled by the vomiting center that causes the contents of the stomach to be forced out through the mouth. Nausea and vomiting can be acute (occurs within minutes to hours after chemotherapy), delayed (develops or continues for 24 hours after chemotherapy and can last for days), or anticipatory. Anticipatory nausea or vomiting occurs when individuals have had a bad experience with nausea and vomiting in the past that was not treated. As a result, they develop nausea and vomiting prior to receiving the next chemotherapy treatments.

While it is not possible to predict the onset, severity, or duration of nausea and vomiting for any one individual, there are certain chemotherapy medications that are more likely to cause nausea and vomiting:

  • Cisplatin
  • Dacarbazine
  • Mechlorethamine
  • Melphalan - in high doses
  • Streptozocin
  • Cytarabine (Ara-C) -- high doses
  • Etoposide -- high doses
  • Carmustine
  • Cyclophosphamide (Cytoxan)
  • Procarbazine
  • Lomustine
  • Dactinomycin
  • Plicamycin
  • Methotrexate -- in high doses
  • Carboplatin
  • Doxorubicin

Factors that may affect the amount and severity of nausea and vomiting include prior experiences with motion sickness, previous bad experiences with nausea and vomiting, being young, and heavy alcohol intake. Women of menstrual age are at greatest risk for severe and long lasting nausea and vomiting.

Many drugs are used alone or in combination to prevent or decrease nausea and vomiting. They include:

  • lorazepam
  • prochlorperazine
  • promethazine
  • metoclopramide
  • dexamethasone
  • ondansetron
  • granisetron

The key to effective nausea and vomiting control is to prevent nausea and vomiting before it occurs. Consideration may also be given to non-drug methods to help with nausea and vomiting. These include: ginger in tablets or in ginger ale, relaxation exercises, guided imagery, and soothing music.

Constipation

Constipation is the passage (usually with discomfort) of infrequent, hard, dry stool. Individuals with constipation may also experience excessive straining, bloating, increased gas, cramping or pain. Constipation affects 50% of people with cancer and 78% with advanced disease. Risk factors include taking narcotic pain medications, decreased physical activity, poor diet, decreased fluid intake and dehydration, bed rest, depression, and certain chemotherapy agents (like vincristine and vinblastine).

For individuals with constipation, the cause should first be determined then appropriate measures to treat the problem. (For information on care measures for constipation related to chemotherapy, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Diarrhea

Diarrhea is the passage of loose or watery stools three or more times a day with or without discomfort. Individuals may also have gas, cramping, and bloating. Diarrhea occurs in 75% of individuals who receive chemotherapy because of the damage to the rapidly dividing cells in the digestive (gastrointestinal) tract. The amount and duration of diarrhea depends on which drugs are given, the drug dose, and length of treatment. Some drugs that cause diarrhea are: 5-fluorouracil, methotrexate, docetaxel, and actinomycin-D. Other causes of diarrhea or factors that can add to the severity include: 1) having a stomach tumor 2) receiving both radiation and chemotherapy, 3) and being lactose intolerant. Diarrhea can be serious and become life-threatening if dehydration, malnutrition, and electrolyte imbalances occur. It is important to report any diarrhea to your doctor or nurse. Keep a record of the number of times you have diarrhea, the amount, and the appearance and give this information to your doctor. (For information on care measures for diarrhea, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Fatigue

Fatigue is a common side effect of cancer and chemotherapy. It is felt as weariness, weakness, lack of energy, and decreased ability for physical and mental work. Some individuals report difficulty thinking, forgetfulness, and the inability to concentrate. Fatigue experienced by a person with cancer is different from the fatigue of everyday life. It is unrelated to activity and is not resolved with rest or sleep. Fatigue can be prolonged and affect the individualís quality of life. (For information about care measures for fatigue, refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Heart Damage

Certain chemotherapy drugs can damage the heart. The most common ones are daunorubicin and doxorubicin (Adriamycin). This occurs in 10% of the individuals who receive these drugs and usually involves changes to the heart muscles. Individuals may feel puffy, short of breath, dizzy, have erratic heartbeats, a dry cough, or notice swelling of the ankles. Individuals who have had past radiation to the mid-chest area, existing heart problems, uncontrolled high blood pressure, and those who smoke will be at higher risk for heart damage. An assessment of a patientís heart function will be done before chemotherapy is started to assure that there are no major problems. During the time of the treatments, heart function is checked to assure that no changes have occurred. Tests such as an electrocardiogram (ECG) or an echocardiogram are done to document any changes in heart function. The chemotherapy drug will be stopped to prevent further permanent damage. Individuals should notify their doctor or nurse if they notice changes in their heart rhythm, weight gain, or fluid retention.

Nervous System Changes

Some chemotherapy drugs can cause direct or indirect changes in the central nervous system (brain and spinal cord), the cranial nerve, or peripheral nerves. The cranial nerves are connected directly to the brain and are important for movement and touch sensation of the head, face, and neck. Cranial nerves are also important for special senses of vision, hearing, taste, and smell. Peripheral nerves are nerves that lead to and from the rest of the body and are important in movement, touch sensation, and regulating activities of some internal organs. Side effects that are the result of nerve damage caused by chemotherapy can occur soon after chemotherapy or years later. Changes involving the central nervous system include stiff neck, headache, nausea and vomiting, lethargy, fever, and confusion.

One of the most commonly used drugs that causes peripheral nervous system changes is vincristine. It causes damage to the nerves. Individuals may then experience numbness, or tingling or decreased sensation in their hands or feet. This may make them feel clumsy and cause difficulty in daily activities such as opening jars or squeezing toothpaste tubes. If the chemotherapy is decreased or stopped, the symptoms will usually decrease or disappear. However, there are times when the damage is permanent.

Damage to the cranial nerves may cause visual difficulties (like blurred vision or double vision), increased sensitivity to odors, hearing loss or ringing in the ears, and dry mouth. Other nervous system changes may include depression, lethargy, sleepiness, and seizures.

Lung Damage

It is possible for some chemotherapy drugs, such as bleomycin, to cause irreversible damage to the lungs. The likelihood of this occurring is increased if the patient receives radiation to the chest in addition to chemotherapy. Age seems to be an important factor in the development of lung damage. For example, individuals over 70 years old have three times the risk of developing lung problems from the drug bleomycin.

Lung damage may result in symptoms such as shortness of breath, a nonproductive (dry) cough, and possibly fever. If the chemotherapy drug is stopped, the lung tissue can regenerate. Since early lung changes may not show up on a chest x-ray, tests such as pulmonary function tests and arterial blood gases, may be performed.

Damage To Reproductive Tissues

Reproductive and sexual problems can occur after receiving chemotherapy. These include temporary or permanent sterility (the inability to have children), irregular menses, lack of menstruation, premature menopause, change in libido (desire for sex), and painful intercourse.

Which, if any, reproductive problems develop depends on the age of the individual when treated, the dose and duration of the chemotherapy, and the chemotherapy drug(s) that are given. Issues of reproduction and sexuality are important because they have implications for patientís futures.

Temporary or permanent sterility may occur due to the effect of chemotherapy drugs on sperm and ova. Some drugs can cause a decrease in the number of viable sperm in men or the lack of ovulation in women. Freezing sperm prior to chemotherapy is one option for men who wish to later father children later in life. Women over 30 years of age are less likely to regain ovarian function. While it is possible to conceive during chemotherapy, the toxicity of some drugs may cause birth defects. Therefore, it is suggested that all men and women take precautions and use some type of birth control if they are sexually active.

Chemotherapy may significantly change a womanís menstrual cycle. Menstruation may stop or become irregular. These irregularities will continue until the drug is stopped.

Painful intercourse may occur for some men and women because some drugs cause a decrease in the moisture of the mucous membranes in the penis and vagina. This is usually temporary. (For care measures, please refer to "Understanding Chemotherapy: A Guide for Patients and Families" by the American Cancer Society.)

Liver Damage

The liver is the organ that metabolizes, or breaks down, most of the chemotherapy drugs that enter the body. Unfortunately, some drugs can cause liver damage. Signs of liver damage include a yellow coloring of to the skin and the whites of the eyes, fatigue, and pain under the lower part of the right ribs or right upper abdomen. Blood tests will be necessary to monitor for possible liver damage. Factors that may increase the likelihood of liver toxicity include increased age and patients who have had hepatitis. Drugs that can cause liver damage include methotrexate, cytarabine (Ara-C), high-dose cisplatin, high-dose cyclophosphamide (Cytoxan), vincristine, vinblastine, and doxorubicin (Adriamycin). Most often the liver damage is temporary and resolves a few weeks after the drug is stopped.

Kidney and Urinary System Damage

Many of the breakdown products of chemotherapy drugs are excreted through the kidneys. These drug byproducts can damage the kidneys, ureters, and bladder. Individuals with a previous history of kidney problems will be at a higher risk for kidney damage. Certain chemotherapy drugs such as cisplatin, high-dose methotrexate, ifosfamide, and streptozocin are more likely to cause kidney and urinary damage than other medications. Signs and symptoms may include headache, pain in the lower back, fatigue, weakness, nausea, vomiting, increased blood pressure, increased rate of breathing, change in pattern of urination, change in color of urine, need to urgently urinate, and swelling or puffiness of the body. Blood tests to measure kidney function are done regularly to watch for any changes.

Long-term Side Effects of Chemotherapy

For many people with cancer, chemotherapy is the best option for controlling their disease. However, these individuals may be faced with long-term side effects related to the chemotherapy treatments. Side effects related to specific chemotherapy drugs can continue after the treatment is completed. These effects can progress and become chronic or new side effects may occur. Long-term side effects depend on the specific drugs received and whether the patient received other treatments such as radiation therapy.

As previously mentioned, certain chemotherapy drugs may cause permanent damage to the bodyís organs. If the damage is detected during treatment, the drug will be discontinued. However, some of the side effects may remain. Damage to some organs and systems, such as the reproductive system, may not be apparent until after chemotherapy is finished.

When young children receive chemotherapy for cancer treatment, it may affect their growth and their ability to learn. Several factors affect long-term side effects, including the age of the patient, the specific drugs that are given, the dosage and length of treatment, and if chemotherapy is used along with other types of treatment such as radiation.

Nervous system changes can develop months or years after treatment. Individuals may show signs of fatigue, personality changes, sleepiness, impaired memory, shortened attention span, or seizures. Hearing loss or tinnitus (ringing in the ears) can be long-term side effects of some drugs. Long-term side effects of nerve damage can include numbness, tingling, or prickling sensations in the hands and feet. Until the immune function returns to normal, individuals are at increased risk for bacterial and viral infections, such as pneumonia and shingles.

Hemorrhagic cystitis (blood in the urine), a side-effect of cyclophosphamide and ifosfamide, can continue for some time after the drug is stopped, and symptoms may become worse.

Development of a second cancer is a great concern for cancer survivors. Secondary cancers can include Hodgkinís disease and non-Hodgkinís lymphoma, leukemias, and some solid tumors. Follow up care after all treatment is completed is an essential component of cancer care for all cancer survivors.

WHAT QUESTIONS SHOULD I ASK MY DOCTORS AND NURSES ABOUT CHEMOTHERAPY?

Specific information about chemotherapy for patients and families can also be obtained from your doctors and nurses. The doctor will decide on the appropriate chemotherapy plan based on the medical history, type of cancer, extent of cancer, current state of health, and current research. Questions you may want to ask your doctor or nurses may include:

  • What chemotherapy medications will I be given?
  • How will I take these drugs (by mouth or through a vein)?
  • How frequently will I need to take chemotherapy?
  • How long will I be receiving chemotherapy treatments?
  • What side effects might I experience?
  • What activities should I do or not do to take care of myself?
  • What long-term effects might I expect?
  • How can I contact you after office hours if I have signs or symptoms that you need to know about?