chemotherapy

Chemotherapy Learn what to expect, and what can be done to improve the experience.

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Definition

Chemotherapy is treatment of cancer with anticancer drugs.

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 their effects on other fast growing cells.

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.

Chemotherapy is usually 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.

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 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 (SQ or SC), which means under the skin. Injection of chemotherapy directly into the cancer is called intralesional (IL) 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 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 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. This method is more common in treatment of certain types of skin cancer.

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.

— Toni Rizzo

1. The treatment of cancer using specific chemical agents or drugs that are selectively destructive to malignant cells and tissues.
2. The treatment of disease using chemical agents or drugs that are selectively toxic to the causative agent of the disease, such as a virus, bacterium, or other microorganism.

Key Terms: Adjuvant therapy, Alkaloid, Alykylating drug, Antiemetic, Antimetabolite, Combination chemotherapy, Lumbar puncture, Peritoneal cavity, Platelets.

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 anticancer 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 anti-cancer 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 5-fluorouracil, also known as 5-FU or fluorouracil. 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), 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 anticancer 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 anticancer 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, adevice 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 microtubules, 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. Preg-nancy 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 antiemetics 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 under-going 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, 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 infectionfighting 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 chemotherapy 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.

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?

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.

Resources

Books

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

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

Other

American Cancer Society. "How Will the Chemotherapy Be Administered?". [cited May 28, 2001]. .

American Cancer Society. Laryngeal and Hypopharyngeal Cancer Resource Center. "How Are Laryngeal and Hypopharyngeal Cancers Treated?" [cited May 28, 2001]. .

Cuesta-Romero, Carlos, and Grado-Pena, Jesus de. "Intralesional Methotrexate in Solitary Keratoacanthoma." Archives of Dermatology, April, 1998. [cited May 28, 2001]. .

National Cancer Institute. National Institutes of Health. "Chemotherapy and You: A Guide to Self-Help During Treatment." .

OncoLink. "Introduction to Chemotherapy." University of Pennsylvania Cancer Center, 1998. .

OncoLink. "What is Chemotherapy?" University of Pennsylvania Cancer Center, September, 1997. .

—Toni Rizzo; Rhonda Cloos, R.N.

Chemotherapy is defined as the use of chemicals to treat any disease, but the term has come to be applied most commonly to the use of drugs to treat cancer. Cancer is an abnormal growth or proliferation of cells that tends to invade locally or spread to distant parts of the body. Several treatment modalities can be used for cancer. Surgery physically removes the abnormal growth, whereas radiation and chemotherapy are directed at killing, or slowing the growth of, cancerous cells.

Paul Ehrlich, a German physician and 1908 Nobel Laureate in Medicine, is generally credited with pioneering the field of chemotherapy and coining the word. However, his efforts were directed toward discovering antibiotics for infections rather than cancer drugs. The first extensively utilized chemotherapy was nitrogen mustard, which was used in the mid-1940s by Alfred Gilman and Frederick S. Philips for the treatment of lymphomas and chronic leukemias. See also Leukemia.

The second group of useful anticancer drugs developed were folic acid antagonists. All actively growing cells require a chemical metabolite called folic acid to grow and divide. The antagonists were designed to inhibit a cancer cell's ability to produce folic acid, and therefore they are toxic. The third group of chemotherapeutic agents was designed to have a toxic effect on the cell's deoxyribonucleic acid (DNA). The development of these drugs was based on the theory that tumor growth might be stopped with chemicals that antagonize nucleic acids which are necessary for cancer cell growth and division. Antitumor antibiotics became recognized as potential chemotherapeutic agents in 1954, when actinomycin D was studied. They differ from antimicrobial antibiotics in that their spectrum of cytotoxicity includes human cells rather than bacteria and fungi. Since the mid-1950s, many new drugs have been developed. The availability of the techniques of molecular biology and a greater understanding of the genetic abnormalities of cancer are resulting in more effective therapies which tend to be more specific for cancer cells. Drugs which inhibit angiogenesis (blood vessel formation) or which target promoting (oncogenes) or suppressing (tumor suppressor) genes are being tested.

Chemotherapeutic drugs come from various sources. They may be extracted from nature, such as from bacteria, fungi, plants, or trees, or they may be chemically synthesized. They may also be semisynthetic, meaning that the process starts with a complex natural compound that is then modified chemically. They may also be produced using modern recombinant DNA technology.

Chemotherapy is used when a cancer has spread to multiple sites and cannot be removed surgically or treated with radiation therapy. It can also be used after all detectable tumor has been eradicated (complete remission) in order to destroy suspected undetectable residual tumor. This type of treatment is called adjuvant, intensification, or consolidation chemotherapy. Adjuvant therapy is effective in breast and colon cancer, and consolidation in acute leukemia, for example. Neoadjuvant chemotherapy is used to shrink a tumor prior to surgery or radiation. The results of treatment depend upon how much chemotherapy is given, how many times it is applied, and how effective it is against the tumor. These facts are derived from a basic principle of chemotherapy that a uniform dose of a drug will destroy a constant fraction rather than a constant number of tumor cells regardless of the size of the tumor or number of cells present (fractional cell kill hypothesis). Regrowth eventually occurs, but each subsequent dose of chemotherapy brings about a further decline in tumor cell number until eventually, in optimal circumstances, the number of tumor cells is low enough for the body to eliminate them by other mechanisms, resulting in a chemotherapy cure. See also Oncology.

Although the different groups of chemotherapeutic agents have different mechanisms of toxicity for cells, the cellular death response is almost always apoptosis, or programmed cell death. In this process a death signal is generated from within the damaged cells. This initiates a series of energy-requiring choreographed cellular events leading to cellular suicide.

The goal of therapy should be determined in all patients who will receive chemotherapy. The possibilities include cure, prolongation of life but not a cure, or palliation (alleviating symptoms) but no prolongation of life. The choice of chemotherapy depends not only upon the type of tumor and the drug efficacy but, most importantly, upon the patient. Also, it must be decided whether the chemotherapy will improve the quality of life of the patient and not just shrink the tumor. Age and the general condition of the patient influence the outcome. Those patients who are more active are more likely to have a favorable outcome to chemotherapy.

The amount of chemotherapy given in each dose is usually based on the size of the body surface in square meters or occasionally just on body weight. The dose must be appropriate for the size of the patient because toxicity often occurs at doses only slightly higher than those needed for therapy. The response of a cancer to a drug is determined by measuring the size of the cancer directly or the amount of marker substances produced by some tumors. A complete response is defined as disappearance of the tumor. A partial response is a decrease in the multiplication product of the two largest diameters by at least 50%. Less than this is considered a failure unless there is an improvement in symptoms. The ultimate measure of response is whether the patients have a prolongation of quality life, which may require observation over a long period of time.

Chemotherapeutic drugs have side effects that are specific for the agent and may include transient or permanent damage to almost any organ system of the body. Chemotherapeutic drugs cause side effects because in addition to destroying the actively dividing cancer cells they damage actively growing normal cells. Common sites of damage are the bone marrow resulting in increased risk for infection, anemia, and bleeding; the gastrointestinal tract resulting in vomiting and diarrhea; the hair follicles causing hair loss; and the kidneys resulting in renal failure. Today, cancer specialists have many ways of preventing or diminishing these toxicities, such as red blood cell transfusions for anemia, drugs to prevent nausea and vomiting, and growth factors which may improve anemia (erythropoietin) or shorten the time of either low white blood counts (granulocyte-colony stimulating factor) or of low platelet counts (thrombopoietin).

Cells can become resistant to drugs of different groups. The general mechanism is referred to as multiple drug resistance. This resistance is due to an acquired ability of the cells to pump these drugs out before they can cause irreversible damage. Most successful modern chemotherapeutic regimens are combinations of drugs. The use of more than one drug increases the chance of a cancer being sensitive to treatment since it is possible that a cancer cell resistant to one drug will be sensitive to another. Drugs can also be combined with other general types of treatment.

There has been a good deal of interest in the specific phase of the cell division cycle that is affected by chemotherapy in the hope that this information could be used to develop more effective cures for cancer. This may eventually lead to effective cell cycle-based drug strategies. Some of the proteins that control the cell cycle (for example, cyclins) might become targets for drug action. Techniques are being developed to ameliorate toxicity so that it may become possible to give higher doses of chemotherapeutic agents. See also Cancer (medicine); Cell cycle.

— broadly speaking, the treatment of disease by chemical means — has had a number of different meanings since Paul Ehrlich (1854-1915) first coined the word in 1907. Then the word referred to the treatment of infectious disease by drugs that killed the infective organism, but left the patient unaffected. This led Ehrlich to postulate the concept he called the ‘magic bullet’ — a medicine that would knock out a precise target, leaving other tissues unharmed. At the beginning of the twenty-first century ‘chemotherapy’ is more usually used to refer to treatment of cancer by powerful chemicals — again based on the original premise of Ehrlich's, that powerful medicinal agents will kill cancerous cells in the body, whilst leaving surrounding cells functioning healthily. In between times, the word gained some currency for the drug treatment of any disease condition.

In the final decades of the nineteenth century, Ehrlich was working on the effects of artificial dyes on living cells, in particular trying to stain parasites in animal tissues. In 1891 he discovered that methylene blue would selectively stain the malaria parasite, which indicated to him that the dyes had combined with some specific receptor sites on the parasite, which might provide a mechanism for treating the disease. By administering the dye to patients with malaria, he showed that this could indeed be used therapeutically in humans; a few years later he found that the dye trypan red showed specific activity against trypanosome infections in mice, although it was not therapeutically effective against trypanosome infections in cattle or humans. From these studies he developed a theory that associated the chemical structure of a synthetic drug with its biological effects. In 1909 he discovered the drug Salvarsan, an arsenical compound that was the first effective drug against the organism that causes syphilis, and he used the word ‘chemotherapy’ to indicate the use of such drugs.

In the early 1930s another chemical agent, Prontosil Red, was discovered, which was shown to be an extremely effective treatment against a number of bacterial infections, including erysipelas, streptococcal angina, and puerperal sepsis. Further chemical research on the compound revealed that Prontosil Red was composed of biologically active and inactive parts, the active component being a readily available chemical, a sulphonamide derivative called sulphanilimide. This was an important discovery: on the one hand, it encouraged chemists to explore the molecular structures of biologically active chenicals, and in particular opened up the sulphonamide molecule to much chemical modification; on the other hand, sulphanilimide was a simple chemical, easy and cheap to prepare, and free from patent restrictions. Its production and use became widespread, as did the use of its derivatives, and the sulphonamides soon provided effective treatments for a wide range of conditions caused by Streptococcus bacteria, including some forms of pneumonia and meningitis. Infections caused by Staphylococcus bacteria, however, such as endocarditis and cellulitis, were resistant to sulphonamides.

The discovery of penicillin in 1928 by the bacteriologist Alexander Fleming (1881-1955), and more importantly, its later effective development by a team in Oxford led by the pathologist Howard Florey (1898-1968) and the chemist Ernst Chain (1906-79), opened up, in the 1940s, a new field of chemotherapy called anti-biosis. This was the use of one microorganism, in this case a mould called Penicillium, to destroy another, such as a disease-causing bacterium. The successful chemical isolation and preparation of the active agent produced by the mould led to the use of the drug during World War II, especially for the treatment of wounded or VD-infected soldiers. Scientifically, the discovery of penicillin stimulated much chemical research to find similar agents — this involved massive screening programmes of a wide range of microorganisms, undertaken by institutes and pharmaceutical companies around the world. It also promoted the further investigation of how penicillin killed bacteria, which was by interfering with the manufacture of the bacterial cell wall. This in turn encouraged research work to find other compounds with the same effect. Gradually, synthetic chemicals were manufactured, which did not therefore fit the precise description of ‘antibiotics’, as they were not produced by microorganisms, although the expression ‘antibiotics’ has continued to be applied to all these medicinal drugs. These antibiotics, whether produced by living organisms, such as mould and fungi, or whether created synthetically in a laboratory, revolutionized the treatment of most infectious diseases. Unfortunately their widespread use has also caused problems, as pathogenic microorganisms are increasingly developing resistance to the powerful drugs designed to kill them. As yet, similar drugs to counteract viral caused diseases have not been produced.

The discovery of the sulphonamide family of drugs in the 1930s coincided with a short period when the word ‘chemotherapy’ was often used to indicate the treatment of any disease with a therapeutic chemical. Thus most modern drug therapy can be regarded, in one sense, as ‘chemotherapy’. Increasingly, however, the word has come to be used now in association with cancer therapies, cancer chemotherapy having the same connotation as the original usage in infectious conditions — the therapeutic agent will destroy the malignancy without affecting surrounding healthy cells and tissues.

Cytotoxic drugs, which destroy rapidly-proliferating cells such as those found in tumours, started being developed, particularly after World War II, especially in the US. Early trials, on diseases such as childhood leukaemia and Hodgkin's disease, were discouraging, the toxic chemicals used almost invariably proving poisonous not only to the cancerous cells but also to normal, unaffected cells. More advanced developments have produced drugs that are effective against a number of cancers, including some that are effective against cancer cells throughout the body, and so can attack cancerous cells that have spread. Several different types of drugs have been developed — alkylating agents, for example, inhibit cell division, whilst anti-metabolites interfere with enzyme systems and block vital processes. These drugs, however, are not readily able to distinguish between healthy and infected cells, and supplementary therapies to protect normal cells and tissues are also given. The concomitant development of drugs to counteract some of the distressing side effects of these powerful medicines, such as nausea and vomiting, hair loss, and fatigue, have also contributed to the success and acceptability of much modern chemotherapy. New fields of research, especially stimulated by developments in understanding the genetic and molecular mechanisms of cancer, have opened up a number of new therapeutic strategies.

— E. M. Tansey

See also cancer; infectious diseases.

A cancer treatment method which uses chemical agents to modify or destroy cancer cells; dental patients who are undergoing chemotherapy may have increased needs for certain nutrients. See also agent, chemotherapeutic.

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

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.

[Article by: Toni Rizzo Teresa G. Odle Angela M. Costello]

For more information on chemotherapy, visit Britannica.com.

Chemotherapy is the treatment of diseases with specific chemical agents. The earliest efforts to use chemotherapy were directed at infectious diseases. Paul Ehrlich, known as the Father of Chemotherapy, reported the clinical efficacy of Salvarsan in 1910, the first agent to be shown effective against syphilis. In 1936, sulfonamides were introduced for the treatment of diseases, such as pneumonia, caused by bacteria. And in 1941, a team of scientists in Oxford, England, isolated the active component of the mold Penicillium notatum, previously shown by Alexander Fleming to inhibit growth of bacteria in culture media. Thereafter, penicillin was manufactured on a large scale in the United States and is still widely used in clinical practice. Subsequent research has led to significant discoveries such as the antibiotics streptomycin, cephalosporins, tetracyclines, and erythromycin, and the antimalarial compounds chloroquine and chloroguanide.

As control of infectious diseases improved, scientists turned their attention to malignant diseases. They sought compounds that would interfere with the metabolism of tumor cells and destroy them. The compounds they discovered work in various ways. Some, such as methotrexate, provide tumors with fraudulent substrates, while others, such as nitrogen mustards, alter tumor DNA to disrupt tumor metabolism and so destroy the malignant cells. Unfortunately, these latter compounds also affect normal tissues, especially those containing rapidly dividing cells, and cause anemia, stomatitis, diarrhea, and alopecia. By careful selection and administration of these chemotherapeutic agents, safer techniques are being developed to prevent the fatal effects of malignant tumors.

Bibliography

Hardman, Joel G., and Lee E. Limbird, eds. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill, 2001.

Higby, Gregory J., and Elaine C. Stroud, eds. The Inside Story of Medicines: A Symposium. Madison, Wisc.: American Institute of the History of Pharmacy, 1997.

Markle, Gerald E., and James C. Petersen, eds. Politics, Science, and Cancer: The Laetrile Phenomenon. Boulder, Colo.: West-view Press, 1980.

Perry, Michael C., ed. The Chemotherapy Source Book. 2d ed. Baltimore: Williams and Wilkins, 1996.

—Peter H. Wright/C. P.

The treatment of disease with chemicals. The term chemotherapy often refers to a kind of treatment for cancer in which chemicals are administered to destroy cancer cells.

The treatment of illness by chemical means; that is, by medication.

• cancer c. — the use of antineoplastic agents in the treatment of malignant growths; usually employed because treatment by other means, such as surgical removal, is not possible. A variety of malignancies in dogs and cats have been successfully managed with some of the chemotherapeutic agents used in the treatment of cancer in humans.
• combination c. — several drugs are used in parallel or in sequence. A common procedure in human cancer therapy.
• multimodal c. — chemotherapy combined with other forms of treatment, e.g. surgical excision.

A woman being treated with docetaxel chemotherapy for breast cancer. Cold mittens and wine coolers are placed on her hands and feet to prevent deleterious effects on the nails. Similar strategies can be used to prevent hair loss.

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals^[1] that kill cells, both good and bad, but specifically those of micro-organisms or cancer. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a cytotoxic standardized treatment regimen. In its non-oncological use, the term may also refer to antibiotics (antibacterial chemotherapy). In that sense, the first modern chemotherapeutic agent was Paul Ehrlich's arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. This was later followed by sulfonamides discovered by Domagk and penicillin discovered by Alexander Fleming.

Most commonly, chemotherapy acts by killing cells that divide rapidly, one of the main properties of cancer cells. This means that it also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract and hair follicles; this results in the most common side effects of chemotherapy—myelosuppression (decreased production of blood cells), mucositis (inflammation of the lining of the digestive tract) and alopecia (hair loss).

Other uses of cytostatic chemotherapy agents (including the ones mentioned below) are the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis and the suppression of transplant rejections (see immunosuppression and DMARDs). Newer anticancer drugs act directly against abnormal proteins in cancer cells; this is termed targeted therapy.

Contents 1 History 2 Principles 3 Treatment schemes 4 Types 4.1 Alkylating agents (L01A) 4.2 Anti-metabolites (L01B) 4.3 Plant alkaloids and terpenoids (L01C) 4.3.1 Vinca alkaloids (L01CA) 4.3.2 Podophyllotoxin (L01CB) 4.3.3 Taxanes (L01CD) 4.4 Topoisomerase inhibitors (L01CB and L01XX) 4.5 Antitumour antibiotics (L01D) 5 Newer and experimental approaches 5.1 Hematopoietic stem cell transplant approaches 5.2 Isolated infusion approaches 5.3 Targeted delivery mechanisms 5.4 Nanoparticles 6 Dosage 7 Delivery 8 Side-effects 8.1 Immunosuppression and myelosuppression 8.2 Nausea and vomiting 8.3 Secondary neoplasm 8.4 Other side effects 9 See also 10 References 11 External links

History

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Further information: History of cancer chemotherapy

The usage of chemical substances and drugs as medication can be traced back to the ancient Indian system of medicine called Ayurveda, which uses many metals besides herbs for treatment of a large number of ailments. More recently, Persian physician, Muhammad ibn Zakarīya Rāzi (Rhazes), in the 10th century, introduced the use of chemicals such as vitriol, copper, mercuric and arsenic salts, sal ammoniac, gold scoria, chalk, clay, coral, pearl, tar, bitumen and alcohol for medical purposes.^[2]

The first drug used for cancer chemotherapy, however, dates back to the early 20th century, though it was not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was studied further during World War II. During a military operation in World War II, a group of people were accidentally exposed to mustard gas and were later found to have very low white blood cell counts^[3]. It was reasoned that an agent that damaged the rapidly-growing white blood cells might have a similar effect on cancer. Therefore, in the 1940s, several patients with advanced lymphomas (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas. Their improvement, although temporary, was remarkable.^[4][5] That experience led researchers to look for other substances that might have similar effects against cancer. As a result, many other drugs have been developed to treat cancer, and drug development since then has exploded into a multibillion-dollar industry. The targeted-therapy revolution has arrived, but the principles and limitations of chemotherapy discovered by the early researchers still apply.^[6]

Principles

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Cancer is the uncontrolled growth of cells coupled with malignant behavior: invasion and metastasis. Cancer is thought to be caused by the interaction between genetic susceptibility and environmental toxins.

In the broad sense, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells they are termed cytotoxic. Some drugs cause cells to undergo apoptosis (so-called "programmed cell death").

Scientists have yet to identify specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast-dividing cells, such as those responsible for hair growth and for replacement of the intestinal epithelium (lining), are also often affected. However, some drugs have a better side effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.

As chemotherapy affects cell division, tumors with high growth fractions (such as acute myelogenous leukemia and the aggressive lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time. Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly.

Drugs affect "younger" tumors (i.e., more differentiated) more effectively, because mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumor cells, differentiation is typically lost, growth becomes less regulated, and tumors become less responsive to most chemotherapeutic agents. Near the center of some solid tumors, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumors is the fact that the chemotherapeutic agent often does not reach the core of the tumor. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery.

Over time, cancer cells become more resistant to chemotherapy treatments. Recently, scientists have identified small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Research on p-glycoprotein and other such chemotherapy efflux pumps, is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing testing as of June, 2007 to enhance the efficacy of chemotherapy.

Treatment schemes

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There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.

Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice that involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent.

In neoadjuvant chemotherapy (preoperative treatment) initial chemotherapy is designed to shrink the primary tumour, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective.

Adjuvant chemotherapy (postoperative treatment) can be used when there is little evidence of cancer present, but there is risk of recurrence. This can help reduce chances of developing resistance if the tumour does develop. It is also useful in killing any cancerous cells which have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.

Palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected.

All chemotherapy regimens require that the patient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required. Because only a fraction of the cells in a tumor die with each treatment (fractional kill), repeated doses must be administered to continue to reduce the size of the tumor^[7]. Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity to the patient^[8].

Types

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The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents.^[9] All of these drugs affect cell division or DNA synthesis and function in some way.

Some newer agents do not directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e.g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors). These are examples of targeted therapies.

In addition, some drugs that modulate tumor cell behaviour without directly attacking those cells may be used. Hormone treatments fall into this category of adjuvant therapies.

Where available, Anatomical Therapeutic Chemical Classification System codes are provided for the major categories.

Alkylating agents (L01A)

Main article: Alkylating antineoplastic agent

Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. Cisplatin and carboplatin, as well as oxaliplatin, are alkylating agents. They impair cell function by forming covalent bonds with the amino, carboxyl, sulfhydryl, and phosphate groups in biologically important molecules.^[9]

Other agents are mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide.^[9] They work by chemically modifying a cell's DNA.

Anti-metabolites (L01B)

Main article: antimetabolite

Anti-metabolites masquerade as purine ((azathioprine, mercaptopurine)) or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics.

Plant alkaloids and terpenoids (L01C)

These alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division, and, without them, cell division cannot occur. The main examples are vinca alkaloids and taxanes.

Vinca alkaloids (L01CA)

Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle). They are derived from the Madagascar periwinkle, Catharanthus roseus (formerly known as Vinca rosea). The vinca alkaloids include:

• Vincristine
• Vinblastine
• Vinorelbine
• Vindesine

Podophyllotoxin (L01CB)

Podophyllotoxin is a plant-derived compound which is said to help with digestion as well as used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action is not yet known.

The substance has been primarily obtained from the American Mayapple (Podophyllum peltatum). Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but, as the plant is endangered, its supply is limited. Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained recombinantively.

Taxanes (L01CD)

The prototype taxane is the natural product paclitaxel, originally known as Taxol and first derived from the bark of the Pacific Yew tree. Docetaxel is a semi-synthetic analogue of paclitaxel. Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase.

Topoisomerase inhibitors (L01CB and L01XX)

Topoisomerases are essential enzymes that maintain the topology of DNA. Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling.

• Some type I topoisomerase inhibitors include camptothecins: irinotecan and topotecan.

• Examples of type II inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide. These are semisynthetic derivatives of epipodophyllotoxins, alkaloids naturally occurring in the root of American Mayapple (Podophyllum peltatum).

Antitumour antibiotics (L01D)

See main article: antineoplastic

These include the immunosuppressant dactinomycin (which is used in kidney transplantations), doxorubicin, epirubicin, bleomycin and others.

Newer and experimental approaches

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Hematopoietic stem cell transplant approaches

Stem cell harvesting and autologous or hematopoietic stem cell transplantation has been used to allow for higher doses of chemotheraputic agents where dosages are primarily limited by hematopoietic damage. Years of research in treating solid tumors, particularly breast cancer, with hematopoeitic stem cell transplants, has yielded little proof of efficacy. Hematological malignancies such as myeloma, lymphoma, and leukemia remain the main indications for stem cell transplants.

Isolated infusion approaches

Isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumours. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic, and, therefore, do not treat distributed metastases or micrometastases.

Targeted delivery mechanisms

Specially-targeted delivery vehicles aim to increase effective levels of chemotherapy for tumor cells while reducing effective levels for other cells. This should result in an increased tumor kill and/or reduced toxicity.

Specially-targeted delivery vehicles have a differentially higher affinity for tumor cells by interacting with tumor-specific or tumour-associated antigens.

In addition to their targeting component, they also carry a payload - whether this is a traditional chemotherapeutic agent, or a radioisotope or an immune stimulating factor. Specially-targeted delivery vehicles vary in their stability, selectivity, and choice of target, but, in essence, they all aim to increase the maximum effective dose that can be delivered to the tumor cells. Reduced systemic toxicity means that they can also be used in sicker patients, and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches.

Nanoparticles

Nanoparticles have emerged as a useful vehicle for poorly-soluble agents such as paclitaxel. Protein-bound paclitaxel (e.g., Abraxane) or nab-paclitaxel was approved by the U.S. Food and Drug Administration (FDA) in January 2005 for the treatment of refractory breast cancer, and allows reduced use of the Cremophor vehicle usually found in paclitaxel. Nanoparticles made of magnetic material can also be used to concentrate agents at tumour sites using an externally applied magnetic field.

Dosage

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Dosage of chemotherapy can be difficult: If the dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity (side effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malignant diseases.

In most cases, the dose is adjusted for the patient's body surface area, a measure that correlates with blood volume. The BSA is usually calculated with a mathematical formula or a nomogram, using a patient's weight and height, rather than by direct measurement.

Delivery

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Most chemotherapy is delivered intravenously, although a number of agents can be administered orally (e.g., melphalan, busulfan, capecitabine). In some cases, isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumour sites without causing overwhelming systemic damage.

Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly-used systems are the Hickman line, the Port-a-Cath or the PICC line. These have a lower infection risk, are much less prone to phlebitis or extravasation, and abolish the need for repeated insertion of peripheral cannulae.

Harmful and lethal toxicity from chemotherapy limits the dosage of chemotherapy that can be given. Some tumours can be destroyed by sufficiently high doses of chemotheraputic agents. However, these high doses cannot be given because they would be fatal to the patient.

Side-effects

The treatment can be physically exhausting for the patient. Current chemotherapeutic techniques have a range of side effects mainly affecting the fast-dividing cells of the body. The most common side effects include (dependent on the agent):^{[citation needed]}

• Pain
• Erythema
• Nausea
• Diarrhea or constipation
• Anemia
• Malnutrition
• Hair loss
• Memory loss
• Depression of the immune system, hence (potentially lethal) infections and sepsis
• Dehydration
• Vertigo
• Hematoma
• Dry mouth/ xerostomia
• Psychosocial distress
• Weight loss or gain
• Hemorrhage
• Water retention
• Sexual impotence
• Secondary neoplasms

Damage to specific organs may occur, with resultant symptoms:

• Cardiotoxicity (heart damage)
• Hepatotoxicity (liver damage)
• Nephrotoxicity (kidney damage)
• Ototoxicity (damage to the inner ear)

Immunosuppression and myelosuppression

Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets. The latter two, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 10⁹/litre) can be improved with synthetic G-CSF (granulocyte-colony stimulating factor, e.g., filgrastim, lenograstim).

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells that produce white and red blood cells) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterwards; in allogenic BMTs the source is a donor.) However, some patients still develop diseases because of this interference with bone marrow.

Nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is common, but use of less emetogenic chemotherapy and better antiemetics have reduced the risks in recent times. Stimulation of the vomiting center in the brain results in the coordination of responses from the diaphragm, salivary glands, cranial nerves, and gastrointestinal muscles to produce the interruption of respiration and forced expulsion of stomach contents known as retching and vomiting. The vomiting center is stimulated directly by afferent input from the vagal and splanchnic nerves, the pharynx, the cerebral cortex, cholinergic and histamine stimulation from the vestibular system, and efferent input from the chemoreceptor trigger zone (CTZ). The CTZ is in the area postrema, outside the blood-brain barrier, and is thus susceptible to stimulation by substances present in the blood or cerebral spinal fluid. The neurotransmitters dopamine and serotonin stimulate the vomiting center indirectly via stimulation of the CTZ.

The 5-HT₃ inhibitors are the most effective antiemetics and constitute the single greatest advance in the management of nausea and vomiting in patients with cancer. These drugs are designed to block one or more of the signals that cause nausea and vomiting. The most sensitive signal during the first 24 hours after chemotherapy appears to be 5-HT₃. Blocking the 5-HT₃ signal is one approach to preventing acute emesis (vomiting), or emesis that is severe, but relatively short-lived. Approved 5-HT₃ inhibitors include Dolasetron (Anzemet), Granisetron (Kytril, Sancuso), and Ondansetron (Zofran). The newest 5-HT₃ inhibitor, palonosetron (Aloxi), also prevents delayed nausea and vomiting, which occurs during the 2-5 days after treatment. A granisetron transdermal patch (Sancuso) was approved by the FDA in September 2008. The patch is applied 24-48 hours before chemotherapy and can be worn for up to 7 days depending on the duration of the chemotherapy regimen.

Another drug to control nausea in cancer patients became available in 2005. The substance P inhibitor aprepitant (marketed as Emend) has been shown to be effective in controlling the nausea of cancer chemotherapy. The results of two large controlled trials were published in 2005, describing the efficacy of this medication in over 1,000 patients.^[10]

Some studies^[11] and patient groups claim that the use of cannabinoids derived from marijuana during chemotherapy greatly reduces the associated nausea and vomiting, and enables the patient to eat. Some synthetic derivatives of the active substance in marijuana (Tetrahydrocannabinol or THC) such as Marinol may be practical for this application. Natural marijuana, known as medical cannabis is also used and recommended by some oncologists, though its use is regulated and not legal everywhere.^[12]

Secondary neoplasm

The development of secondary neoplasia after successful chemotherapy and or radiotherapy treatment has shown to exist. The most common secondary neoplasm is secondary acute myeloid leukemia, which develops primarily after treatment with alkylating agents or topoisomerase inhibitors.^[13] Other studies have shown a 13.5 fold increase from the general population in the incidence of secondary neoplasm occurrence after 30 years from treatment.^[14]

Other side effects

In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side effect that can lead to death if left untreated.

Some patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, referred to as "chemo brain" by patients' groups.^[15]

Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g., MOPP therapy for Hodgkin's disease).

See also

• Cancer
• Gene therapy
• Experimental cancer treatments
• Chemotherapy regimens
• National Comprehensive Cancer Network
• Safe Handling of Hazardous Drugs

References

1. ^ chemotherapy at Dorland's Medical Dictionary
2. ^ The Valuable Contribution of al-Razi (Rhazes) to the History of Pharmacy, FSTC.
3. ^ Hirsch J (September 2006). "An anniversary for cancer chemotherapy". JAMA 296 (12): 1518–20. doi:10.1001/jama.296.12.1518. PMID 17003400. 
4. ^ Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. (1946). "Nitrogen mustard therapy". JAMA 132: 26–32. 
5. ^ Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. (1984). "Landmark article Sept. 21, 1946: Nitrogen mustard therapy. Use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. By Louis S. Goodman, Maxwell M. Wintrobe, William Dameshek, Morton J. Goodman, Alfred Gilman and Margaret T. McLennan". JAMA 251 (17): 2255–61. PMID 6368885. 
6. ^ Joensuu H. (2008). "Systemic chemotherapy for cancer: from weapon to treatment". Lancet Oncol. 9 (3): 304. doi:10.1016/S1470-2045(08)70075-5. PMID 18308256. 
7. ^ Skeel, R. T. (2003). Handbook of Cancer Chemotherapy, Lippincott Williams & Wilkins.
8. ^ Chabner, B. and D. L. Longo (2006). Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, Lippincott Willians & Wilkins.
9. ^ ^{a b c} Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
10. ^ Gralla R, de Wit R, Herrstedt J, Carides A, Ianus J, Guoguang-Ma J, Evans J, Horgan K (2005). "Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials". Cancer 104 (4): 864–8. doi:10.1002/cncr.21222+. PMID 15973669. 
11. ^ Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001;323:16-21. PMID 11440936.
12. ^ "Frequently Asked Questions - Medical Marihuana"
13. ^ U. Rüther, C. Nunnensiek, H.-J. Schmoll,Secondary Neoplasias following Chemotherapy, Radiotherapy, and Immunosuppression,Contributions to Oncology (Beiträge zur Onkologie); Vol 55, 2000, ISBN 380557116X
14. ^ Hijiya, Hudson, Lensing et al. Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic LeukemiaJAMA, 2007;297:1207-1215.
15. ^ Tannock IF, Ahles TA, Ganz PA, Van Dam FS (June 2004). "Cognitive impairment associated with chemotherapy for cancer: report of a workshop". J. Clin. Oncol. 22 (11): 2233–9. doi:10.1200/JCO.2004.08.094. PMID 15169812. http://www.jco.org/cgi/pmidlookup?view=long&pmid=15169812. 

External links

• American Cancer Society - Chemotherapy
• Cancerbackup - Understanding Chemotherapy
• The leukemia and lymphoma society
• Chemotherapy.com Educational and support information about chemotherapy and associated side effects
• Cancer Management Handbook: Principles of Oncologic Pharmacotherapy
• Several cancer related dictionaries

v • d • e Intracellular chemotherapeutic agents/antineoplastic agents (L01) SPs/MIs (M phase) Block microtubule assembly Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine) Block microtubule disassembly Taxanes (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) · Epothilones (Ixabepilone) DNA replication inhibitor DNA precursors/ antimetabolites (S phase) Folic acid dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed) · thymidylate synthase inhibitor (Raltitrexed, Pemetrexed) Purine adenosine deaminase inhibitor (Pentostatin) halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine) thiopurine (Thioguanine, Mercaptopurine) Pyrimidine thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine) DNA polymerase inhibitor (Cytarabine) ribonucleotide reductase inhibitor (Gemcitabine) hypomethylating agent (Azacitidine, Decitabine) Deoxyribonucleotide ribonucleotide reductase inhibitor (Hydroxyurea) Topoisomerase inhibitors (S phase) I Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan) II Podophyllum (Etoposide, Teniposide) II+Intercalation Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) · Anthracenediones (Mitoxantrone, Pixantrone) Crosslinking of DNA (CCNS) Alkylating Nitrogen mustards: Mechlorethamine · Cyclophosphamide (Ifosfamide, Trofosfamide) · Chlorambucil (Melphalan, Prednimustine) · Bendamustine · Uramustine · Estramustine Nitrosoureas: Carmustine · Lomustine (Semustine) · Fotemustine · Nimustine · Ranimustine · Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan) Aziridines: Carboquone · ThioTEPA · Triaziquone · Triethylenemelamine Alkylating-like Platinum (Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin) Nonclassical Hydrazines (Procarbazine) · Triazenes (Dacarbazine, Temozolomide) · Altretamine · Mitobronitol Intercalation Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) Photosensitizers/PDT Aminolevulinic acid/Methyl aminolevulinate · Efaproxiral · Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin) Other Enzyme inhibitors FI (Tipifarnib)  · CDK inhibitors (Alvocidib, Seliciclib) · PrI (Bortezomib) · PhI (Anagrelide) · IMPDI (Tiazofurine) · LI (Masoprocol) · PARP inhibitor (Olaparib) Receptor antagonists ERA (Atrasentan) · retinoid X receptor (Bexarotene) · sex steroid (Testolactone) Other/ungrouped Amsacrine · Trabectedin · retinoids (Alitretinoin, Tretinoin) · Arsenic trioxide · asparagine depleter (Asparaginase/Pegaspargase) · Celecoxib · Demecolcine · Elesclomol · Elsamitrucin · Etoglucid · Lonidamine · Lucanthone · Mitoguazone · Mitotane · Oblimersen · Temsirolimus · Vorinostat

v • d • e Targeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01) CI monoclonal antibodies ("-mab") Receptor tyrosine kinase ErbB: HER1/EGFR (Cetuximab, Panitumumab) · HER2/neu (Trastuzumab) Others for solid tumors EpCAM (Catumaxomab, Edrecolomab) · VEGF-A (Bevacizumab) Leukemia/lymphoma lymphoid: CD20 (Rituximab, Tositumomab, Ibritumomab) myeloid: CD52 (Alemtuzumab) L+M: CD33 (Gemtuzumab) Tyrosine kinase inhibitors ("-nib") Receptor tyrosine kinase ErbB: HER1/EGFR (Erlotinib, Gefitinib, Lapatinib, Vandetanib, Neratinib) · HER2/neu (Lapatinib, Neratinib) RTK class III: C-kit (Axitinib, Sunitinib, Sorafenib, Toceranib) · FLT3 (Lestaurtinib) · PDGFR (Axitinib, Sunitinib, Sorafenib, Toceranib) VEGFR (Vandetanib, Semaxanib, Cediranib, Axitinib, Sunitinib, Sorafenib, Toceranib) Non-receptor bcr-abl (Imatinib, Nilotinib, Dasatinib) Src (Bosutinib) Janus kinase 2 (Lestaurtinib) Other fusion protein against VEGF (Aflibercept) · exotoxin against IL-2 (Denileukin diftitox)

v • d • e Pathology: Tumor, Neoplasm, Cancer, and Oncology (C00-D48, 140-239) Benign tumors Hyperplasia · Cyst · Pseudocyst · Hamartoma Malignant progression Dysplasia · Carcinoma in situ · Cancer · Metastasis Topography Oral · Head/Neck · Nasopharyngeal · Digestive system · Respiratory system · Bone · Skin · Blood · Urogenital · Nervous system · Endocrine system Histology Carcinoma · Sarcoma · Papilloma · Adenoma Misc. Tumor suppressor genes/oncogenes · Staging/grading · Carcinogenesis · Carcinogen · Research · Precancerous condition · Paraneoplastic syndrome · List of oncology-related terms

v • d • e Major drug groups Gastrointestinal tract/metabolism (A) stomach acid (Antacids, H2 antagonists, Proton pump inhibitors) • Antiemetics • Laxatives • Antidiarrhoeals/Antipropulsives • Anti-obesity drugs • Anti-diabetics • Vitamins • Dietary minerals Blood and blood forming organs (B) Antithrombotics (Antiplatelets, Anticoagulants, Thrombolytics/fibrinolytics) • Antihemorrhagics (Platelets, Coagulants, Antifibrinolytics) Cardiovascular system (C) cardiac therapy/antianginals (Cardiac glycosides, Antiarrhythmics, Cardiac stimulants) Antihypertensives • Diuretics • Vasodilators • Beta blockers • Calcium channel blockers • renin-angiotensin system (ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors) Antihyperlipidemics (Statins, Fibrates, Bile acid sequestrants) Skin (D) Emollients • Cicatrizants • Antipruritics • Antipsoriatics • Medicated dressings Reproductive system (G) Hormonal contraception • Fertility agents • SERMs • Sex hormones Endocrine system (H) Hypothalamic-pituitary hormones • Corticosteroids (Glucocorticoids, Mineralocorticoids) • Sex hormones • Thyroid hormones/Antithyroid agents Infections and infestations (J, P, QI) Antibiotics • Antimycobacterials (Tuberculosis treatment, Leprostatic agents) • Antifungals • Antivirals • Vaccines • Antiparasitics (Antiprotozoals, Anthelmintics) • Ectoparasiticides Malignant disease (L01-L02) Anticancer agents (Antimetabolites, Alkylating, Spindle poisons, Antineoplastic, Topoisomerase inhibitors) Immune disease (L03-L04) Immunomodulators (Immunostimulants, Immunosuppressants) Muscles, bones, and joints (M) Anabolic steroids • Anti-inflammatories (NSAIDs) • Antirheumatics • Corticosteroids • Muscle relaxants • Bisphosphonates Brain and nervous system (N) Anesthetics (General, Local) • Analgesics • Antimigraines • Anticonvulsants/Mood stabilizers (Lithium pharmacology) • Antiparkinson drugs Psycholeptics (Anxiolytics, Antipsychotics, Hypnotics/Sedatives) • Psychoanaleptics (Antidepressants, Stimulants) Respiratory system (R) Decongestants • Bronchodilators • Cough medicines • H1 antagonists Sensory organs (S) Ophthalmologicals • Otologicals Other ATC (V) Antidotes • Contrast media • Radiopharmaceuticals • Dressings

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Dansk (Danish)
n. - kemoterapi

Nederlands (Dutch)
chemotherapie

Français (French)
n. - chimiothérapie

Deutsch (German)
n. - Chemotherapie

Ελληνική (Greek)
n. - χημειοθεραπεία

Italiano (Italian)
chemioterapia

Português (Portuguese)
n. - quimioterapia (f)

Русский (Russian)
химиотерапия

Español (Spanish)
n. - quimioterapia

Svenska (Swedish)
n. - kemoterapi

中文（简体）(Chinese (Simplified))
化学疗法

中文（繁體）(Chinese (Traditional))
n. - 化學療法

한국어 (Korean)
n. - 화학 요법

日本語 (Japanese)
n. - 化学療法

العربيه (Arabic)
‏(الاسم) علاج كيماوي, المداواة الكيميائيه المصليه‏

עברית (Hebrew)
n. - ‮כימותראפיה, ריפוי בחומרים כימיים‬

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