Chemotherapy

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I INTRODUCTION
Chemotherapy, treatment of an illness or other medical condition using drugs. The term most commonly refers to the treatment of cancer using specific drugs designed to destroy cancer cells, thereby slowing or reversing the growth rate of tumors. The drugs used in chemotherapy attack a specific tumor, but they also travel to the entire body through the bloodstream, destroying cancerous cells that have spread and which might otherwise form new tumors.
Chemotherapy is just one of the weapons used to treat cancer. Depending on the type of cancerous growth and its location in the body, oncologists (physicians who specialize in cancer treatment) can also use surgery to remove tumors. Another treatment is radiation, using concentrated X rays or other energy particles to destroy cancer cells (see Radiology). Unlike chemotherapy, however, surgery and radiation are local treatments only, useful for attacking a specific tumor and any cancerous threat in immediately surrounding tissue.
Many of the chemotherapeutic drugs used today are cytotoxic (cell-killing) for both malignant and normal cells. As normal cells die off, unpleasant side effects commonly result. But current biomedical research is making considerable strides in designing and introducing new drugs that specifically attack cancer cells while not affecting healthy cells. Such drugs have already begun to transform cancer treatment. Chemotherapy has achieved marked success in curing some forms of cancer, including Hodgkin’s disease, non-Hodgkin’s lymphoma, some forms of leukemia, and testicular cancer. It has also, alone or in combination with other forms of therapy, achieved significant results against cancers of the breast, ovary, and bladder.
II HOW CHEMOTHERAPY WORKS
At any given moment in the human body, billions of healthy cells undergo a balanced, orderly cycle of renewal and replacement. Old cells die and new ones—created through the process of cell division—take their place. In cancerous cells, however, the mechanisms regulating cell division break down, and cells divide rapidly without control, ultimately massing into tumors.
Chemotherapy drugs work by interfering with this cell cycle. Some drugs affect specific phases of the cell cycle, such as the replication of deoxyribonucleic acid (DNA), the coiled molecule that contains the cell’s hereditary instructions. Other drugs attack cancerous cells at any part of the cell cycle. Chemotherapeutic drugs have the greatest effect on cells that undergo rapid division. While this means that the drugs effectively kill cancerous cells, they also attack healthy cells that tend to divide rapidly, such as those found in hair follicles, the mouth, the digestive system, and bone marrow.
As these healthy cells die, unpleasant side effects develop. One common side effect is hair loss. Sores of the mouth are another frequent side effect. Nausea and vomiting are also common, due to the drugs’ effect on the cells of the stomach and other organs of the digestive system. Antinausea and antianxiety drugs can help with these symptoms. If chemotherapy affects the bone marrow, the production of infection-fighting white blood cells of the immune system is reduced or halted. Physicians must carefully monitor a chemotherapy patient’s white-cell count and be prepared to treat opportunistic infections, usually harmless infections that can overwhelm the body and cause disease in those with damaged immune systems.
III TYPES OF CHEMOTHERAPY
There are several types of chemotherapeutic drugs available for the treatment of malignancies. Alkylating agents, for example, are effective in all phases of the cell cycle. These drugs bind to DNA inside the cell and prevent the cell from dividing. Alkylating agents are used to treat cancers of the lymph system (such as Hodgkin’s disease), certain forms of leukemia, and other malignancies.
Drugs in the class known as nitrosoureas interfere with DNA repair. They are primarily used in treating brain cancer. Another group of chemotherapy drugs, referred to as antimetabolites, interfere with cell replication by preventing the cell from assembling the building blocks of DNA and ribonucleic acid (RNA), the molecule that directs protein synthesis. Antimetabolites are used to treat breast cancer, ovarian cancer, and cancers of the gastrointestinal tract.
Mitotic inhibitors constitute another class of chemotherapeutic agents. As their name implies, these drugs interfere with mitosis, the part of the cell cycle when the cell actually divides. These agents are used to treat lung cancer, breast cancer, and testicular cancer. Another class of cancer drugs, known as antitumor antibiotics, treat a variety of cancers, including leukemias. These drugs work by inhibiting the synthesis of RNA.
Still another class of drugs works by raising or lowering the body’s production and processing of sex hormones. These naturally occurring substances can increase or inhibit the growth of tumors. For instance, some breast and ovarian cancers in females need estrogen to grow, while prostate cancer in males needs testosterone to grow. Some chemotherapeutic compounds, therefore, are designed to interfere with these hormones. The drug tamoxifen, for example, blocks the action of estrogen in females and is used to treat breast cancer.
IV HOW CHEMOTHERAPY IS ADMINISTERED
A cancer patient often receives two or more chemotherapy drugs at the same time. Such combination therapy provides a maximum assault on cancer cells, since each drug attacks different parts of the cell cycle. This approach enables physicians to prescribe lower dosages of each drug than would be needed if one drug was used alone, lessening the toxic side effects of chemotherapy. Combination therapy can also prevent cancer cells from developing resistance to chemotherapeutic agents, as might occur after prolonged exposure to a single drug.
Chemotherapy is also frequently combined with surgery and radiation to fight cancer. In some instances, chemotherapy can render cancer cells more prone to the effects of radiation. Chemotherapy can also enhance the effects of surgery, since the drugs can reach and destroy cancerous cells near the site of a surgically removed tumor. Ideally, the combination of surgery, radiation, and chemotherapy will attack and neutralize cancer while maintaining as much of the body’s healthy cells and tissue as possible.
Depending on the drug and the type of cancer, chemotherapy can be administered in pill form or by a needle injected into a muscle, under the skin, or into a vein (known as an intravenous injection). In the case of an intravenous injection, the drug may be injected into the body all at once or allowed to drip slowly into the body from a bag suspended above the patient.
To save a patient from repeated sticks of a needle each time an intravenous drug is given, doctors sometimes install vascular access devices. One such device consists of a flexible tube called a catheter. One end of the catheter is inserted under the skin and the other end is attached to a port, an opening through which medicine is inserted. The catheter permits not only the administration of drugs but also the drawing of blood. Ports can also be surgically inserted beneath the skin, often near the collarbone. Some patients use miniature pumps containing chemotherapy drugs. These pumps are small enough to fit unobtrusively in a pocket or on a belt, enabling patients to leave a treatment facility and go about their normal routines while the pump automatically feeds a steady dosage of drugs through a port.
Chemotherapy is usually administered in cycles, in which treatment periods alternate with periods when the body is given the chance to rest and recover. Chemotherapy schedules vary widely, depending on the patient’s illness. One patient may receive medication one day a month, another patient five times a week, and another in three-week intervals. An entire course of chemotherapy treatment can last from a matter of weeks to several months or longer.
V IMPROVING THE EFFECTIVENESS OF CHEMOTHERAPY
Some forms of cancer, including malignancies of the brain, prostate, and pancreas, do not respond well to cancer drugs. Biomedical scientists continually pursue new, more effective chemotherapeutic agents. For example, they have developed new compounds designed for pinpoint specificity, intended to shut down cancer cells while not affecting healthy ones. One such drug is imatinib mesylate (sold under the brand name Gleevec), which interferes with an essential protein of malignant cells in chronic myelogenous leukemia. Another approach involves zeroing in on specific molecules on the surface of cancer cells and inducing the cells to self-destruct through apoptosis (the natural process of cell death to make way for new cells). These and other strategies are constantly expanding the range of weapons in the anticancer arsenal.

Chemotherapy Side Effects

In the last 20 years, scientists have made a great deal of progress in developing therapies to help prevent and manage the side effects of chemotherapy. Newer supportive care treatments have led to vast improvements in the management of symptoms associated with cancer treatment. Many people don't experience side effects at all, and you are unlikely to experience all the side effects you read about below. All chemotherapy options are designed to treat cancer; unfortunately, they often affect parts of your body not directly affected by the cancer itself. This undesired result is referred to as a complication of treatment, or a side effect.

Side effects may be acute (short-term), chronic (long-term), or permanent. Side effects may cause inconvenience, discomfort, and even death.

Additionally, certain side effects may prevent doctors from delivering the prescribed dose of chemotherapy at the specific time and schedule of the treatment plan.3,11,12 Since the expected outcome from chemotherapy is based on delivering the full chemotherapy dose on schedule, it is important to understand chemotherapy cycles and schedules.

Side effects from chemotherapy can include pain, diarrhea, constipation, mouth sores, hair loss, nausea and vomiting, as well as blood-related side effects. In this section, you can learn more about the importance in diagnosing and monitoring blood-related side effects. These may include low white blood cell count (neutropenia), low red blood cell count (anemia), low platelet count (thrombocytopenia), and related fatigue.

CBC and Related Side Effects

The CBC, or complete blood count, helps your doctor look for side effects of chemotherapy, which include changes in the three types of cells in your blood. Because chemotherapy kills fast-growing blood cells as well as cancer cells, side effects involving your blood are an almost-to-be-expected result of chemotherapy. Your first step in managing blood-related side effects is understanding CBC, or your complete blood count.

Side effects involving blood include the following:

Neutropenia

Neutropenia (new-troh-PEE-nee-ah) is the scientific name for a low infection-fighting white blood cell count. A low white blood cell count may leave your body vulnerable to infection and too weak to receive chemotherapy at the full dose on schedule.3,11,12 This could lead your doctor to delay your current treatment or reduce your doses until your count reaches sufficient levels. If not properly treated, infection can lead to hospitalization. To help reduce the risk of treatment delays due to blood-related side effects, find out more about the risks associated with low white cell blood count.

Anemia

Anemia (ah-NEE-mee-ah) is the scientific name for a low red blood cell count. A low red blood cell count may cause you to feel fatigued or sluggish because there is not enough oxygen circulating in your body. This condition can be effectively managed with one of several treatments, including blood transfusion if necessary. There are also other ways to manage low red blood cell count.

Thrombocytopenia

Thrombocytopenia (throm-boh-sy-toh-PEE-nee-ah) is the scientific name for a low platelet count. A low platelet count may cause you to experience bruising or excessive bleeding. Learn more about the risks of low platelet count.

All of these side effects may be related to your chemotherapy. All are diagnosed through your CBC test. You can manage them to help reduce the possibility that they will compromise your treatment. A journal provides a place for you to keep track of your blood counts throughout your chemotherapy, and is one of the Tools for Organizing Your Cancer Information.


In addition to blood-related side effects, chemotherapy can result in other side effects that can interfere with treatment if not managed properly. Learn more about other types of chemotherapy side effects.

Sometimes side effects signal a serious problem. Find out when to call your doctor about chemotherapy side effects.

Basic concepts

An ideal chemotherapeutic agent is one that is cidal (kills) rather than static (inhibiting growth). It should affect a specific microbe or tissue cell and not affect other microbes or normal cells. It should be one to which the infectious organism or cancer does not become resistant and one that is not allergic or toxic to the host. An ideal chemotherapeutic agent must have pharmacological attributes favourable for its use. Therefore, if it is to affect organisms in the gastrointestinal tract, it must remain in the intestinal tract and not be absorbed or inactivated when given orally. If an oral drug is used to affect organisms in the blood or tissues, then it must be absorbed from the intestinal tract or it must be capable of being given parenterally (by injection). It must be able to penetrate tissues and be maintained for adequate periods of time at the site of the infection or cancer in concentrations sufficient to affect the microorganism or cancer cells.

The factors that affect these conditions are molecular size, ionic charge, rate of metabolism and excretion (half-life), lipid solubility, degree of protein binding, and presence or absence of inflammation in the tissue. The chemotherapeutic agent must be selectively toxic; that is, it should be active against the microorganism or cancer cell but it must not be toxic for the host in the amount administered.

None of the chemotherapeutic agents presently in use meets all of these criteria. In fact, a number of compounds that produce significant toxic effects in humans are used because theyhave a favourable chemotherapeutic index; that is, the amount required for a therapeutic effect is below the amount that causes a toxic effect. The levels of these drugs in the patient must be carefully controlled so as not to exceed toxic levels.

Persons with certain altered organ functions, such as occurs in liver or kidney disease, are often especially susceptible to drug toxicity. Chemotherapeutic agents, however, can be usedsafely if drug concentrations in blood are measured, the dose adjusted to avoid toxic levels, and organ function or toxicity monitored closely.

Chemotherapeutic agents that are used in the treatment of disease are of three sources: (1) the synthetic chemicals; (2) chemical substances or metabolic products made by microorganisms, a group containing the antibiotics; and (3) plants.

All chemotherapeutic agents can have adverse effects ranging from relatively harmless to serious and life-threatening, sometimes culminating in death. These effects can be due to direct toxicity; allergic or hypersensitivity reactions; or alterations in the numbers and types of micoorganisms that are the normal flora found in the mouth, intestine, vagina, skin, etc.

Direct toxicities are expressed in a variety of ways, and many of these are associated with the gastrointestinal tract (nausea, vomiting, and diarrhea) and skin rashes. They are usually minor and do not limit the use of the agent. In more extreme cases, the toxicities can result in serious damage to organs such as the kidneys, liver, and eyes and to the nervous system. Some chemotherapeutic agents affect normal red blood cells, which can result in anemia. Allergic or hypersensitivity reactions can range from minor effects such as skin rash and itching to more serious effects that include choking and difficulty in breathing. In some cases,a sudden and severe form of allergy (anaphylaxis) can result in death.

The use of antimicrobial agents, in particular the broad-spectrum agents (see below Antibacterial drugs), can result in an alteration in the number and type of microorganisms normally found on the skin and mucosal surfaces. This is due to the inhibitory activity of the antimicrobial agent on sensitive microorganisms found on these tissues. The eradication of some organisms relieves the inhibitory activity they have on each other, thereby allowing thesurviving (resistant) organisms to multiply. In some cases, organisms such as yeast that are generally resistant to antibiotics increase to numbers sufficient to invade and infect tissue.

Cancer chemotherapy

New approaches to cancer chemotherapy

Other agents being evaluated include interferon and monoclonal antibodies. Interferon is an antiviral agent that is effective in some cancers. Monoclonal antibodies are highly specific agents that recognize differences between cells. The approach to their use is twofold: first, touse the antibody to kill cancer cells by direct action; and second, to couple a toxin to the antibody. The antibody is used to recognize a specific cancer cell and to deliver a toxin that kills it.

The BCG vaccine is an attenuated form of the bacillus that causes tuberculosis. It is used to immunize selected persons so as to prevent tuberculosis, and it has been used in the treatment of certain forms of cancer. Other chemicals are used to enhance the immunity to cancer cells.

The decision to use a certain antineoplastic drug depends on many factors, including the typeand location of the cancer, its severity, whether surgery or radiation therapy can or should be used, and the side effects associated with the drug. Combinations of anticancer drugs, like combinations of antimicrobials, are often more effective than single agents. Although many regimens have been developed, each must be tailored to the patient.

Treating Cancer With Chemotherapy

Many people fear chemotherapy because they have heard that it can have uncomfortable side effects. But side-effect management has come a long way over the last few decades. Today, many side effects once associated with chemotherapy can be prevented or controlled. With some types of chemotherapy, you may experience only minimal side effects. And chemotherapy may be your best option for a successful outcome. You can help achieve a successful outcome by understanding how side effects can impact your treatment. Learn how best to manage chemotherapy side effects.

Chemotherapy is the general term for any treatment involving the use of chemical agents to stop cancer cells from growing. Chemotherapy can eliminate cancer cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.

More than half of all people diagnosed with cancer receive chemotherapy. For millions of people, chemotherapy helps treat their cancer effectively, enabling them to enjoy full, productive lives.

A chemotherapy regimen (a treatment plan and schedule) usually includes drugs to fight cancer plus drugs to help support completion of the cancer treatment at the full dose on schedule. Most doctors agree that staying on your chemotherapy schedule gives you the best opportunity for a successful result.2-8

To get the most from chemotherapy, it's important to stick to a schedule of treatment. Find out more about chemotherapy cycles and schedules.

How Chemotherapy Works

Chemotherapy is designed to kill cancer cells. Chemotherapy can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill, depending on which drug is used.

Chemotherapy works by destroying cancer cells; unfortunately, it cannot tell the difference between a cancer cell and some healthy cells. So chemotherapy eliminates not only the fast-growing cancer cells but also other fast-growing cells in your body, including, hair and blood cells.

Some cancer cells grow slowly while others grow rapidly. As a result, different types of chemotherapy drugs target the growth patterns of specific types of cancer cells. Each drug has a different way of working and is effective at a specific time in the life cycle of the cell it targets. Your doctor will determine the chemotherapy drug that is right for you. To understand more about the different ways chemotherapy is given, read about how people receive chemotherapy.

Discussing the Effectiveness of Cancer Treatment

Understand the goals and risks of each treatment option so you can work with your doctor to decide which treatment is best for you. Balance potential benefits against the risks of treatment.

Some risks of cancer treatments may include time away from family and friends, uncomfortable side effects, or long-term complications. Cancer treatment may be inconvenient, prolonged, or unavailable close to home. These are important considerations when evaluating treatment options, but they are not typically mentioned in medical journals reporting the results and benefits of new treatments.

Once you and your doctor have decided on a treatment plan, talk with your doctor about all you can do to make sure you get the full dose of your cancer treatment on schedule. You can make note of subjects to discuss and questions to ask by using Tools for Organizing Your Cancer Information.

Importance of Full Dose on Schedule

Studies show that for certain types of cancer, chemotherapy produces the best long-term results when patients receive the full dose on time, every time.

Your doctor will develop a treatment plan scientifically designed for you, based on your type of cancer, its stage of advancement, and your overall health. It will consist of specific chemotherapy agents, at specific doses and intervals. These are called your scheduled cycles. Generally, treatments are given daily, weekly, or monthly. Your doctor will help you determine the most effective treatment schedule for you.

The goal is to make your chemotherapy as effective, timely, and problem-free as possible. But while your chemotherapy treatment works to fight your cancer, it also can cause side effects such as a lowered white blood cell count. A low white blood cell count means your immune system isn't as strong as it could be, which can increase your risk of infection. It also can require your doctor to change your dose or schedule of your chemotherapy.

A chemotherapy-induced low white blood cell count, caused by healthy cells lost during chemotherapy, is an expected side effect of your treatment. Therefore, you can plan ahead so it is less likely to disrupt your treatment schedule. A low white blood cell count typically occurs after the administration of certain types of chemotherapy and may continue for several days. To help reduce side effects like low white blood cell count that may interfere with your treatment schedule, learn more about managing chemotherapy side effects.

Under certain circumstances, your doctor may decide your body is too weak to receive chemotherapy. A low white blood cell count can temporarily disrupt your cancer treatment or result in having your chemotherapy dose decreased. These changes to your treatment plan could make your cancer treatment less effective than it should be.

To get the most from chemotherapy, it's important to stick to a schedule of treatment. Find out about chemotherapy cycles and schedules.

Chemotherapy Side Effects

An undesirable consequence of chemotherapy affecting your body—not related to your cancer—is referred to as a complication of treatment, or a side effect. Some common side effects of chemotherapy are:
Low white blood cell count
Low red blood cell count
Low platelet count
Nausea
Vomiting
Hair loss
Fatigue
Some side effects may be temporary and uncomfortable. Some can cause dose reductions and treatment delays or even be life-threatening.

For example, one of the most serious potential side effects of chemotherapy is a low count of infection-fighting white blood cells—a condition called neutropenia (new-troh-PEE-nee-ah). Neutropenia can interrupt your chemotherapy schedule and put you at risk for infections that may require hospitalization and may even be life-threatening.

Fortunately, significant progress has been made in the development of "proactive" therapies that help you manage the side effects of chemotherapy—ideally, before they interrupt your treatment schedule.

Take an active role in managing side effects. Learn all you can, use your tools for organizing your cancer information to note any side effects you experience, and be sure to discuss them with your doctor. You can make note of subjects to discuss and questions to ask by using your Tools for Organizing Your Cancer Information.


Full Dose on Schedule

Certain side effects may prevent doctors from delivering your full dose of chemotherapy on schedule.

This can be a problem, since your best results typically depend on receiving treatment at the full dose and on your scheduled plan.







Impact of Delaying Treatment or Reducing Doses

A 2003 study reported in The Journal of Clinical Oncology by Dr. Gary Lyman, an oncologist and Professor at the University of Rochester, New York, found that many breast cancer patients did not receive the full doses of their chemotherapy on schedule.13
Most delays and reductions in the planned doses of chemotherapy were due to concerns about side effects.

Delays or reductions in the planned doses of chemotherapy were likely to affect the likelihood of a successful outcome.
In many cases, such delays and reductions were preventable.

"The odds of curing breast cancer are highest when a patient completes a full course of chemotherapy," concluded Dr. Lyman.
This study was funded by Amgen.










How People Receive Chemotherapy

People receive chemotherapy in one of the following four (4) ways, or a combination of them:
Intravenous (IV) infusion
Pill
Injection or shot
Intrathecal and intraventricular injection, which means a shot into the fluid surrounding the spinal cord or brain
You can receive many types of chemotherapy at home. Through instruction, you and your family members can learn how to administer chemotherapy in pill form or by injection with small syringes and needles similar to those that people with diabetes use to administer insulin.

In some cases, a nurse will administer chemotherapy in an outpatient clinic. In other cases, it may be necessary to go to the hospital to receive treatment.

Because different drugs damage cancer cells during different times, combining different chemotherapy drugs into a regimen can result in more cancer cells being killed and improve your outcome.

Chemotherapy is not without risk of side effects. Learn how best to manage chemotherapy side effects.



Chemotherapy Cycles and Schedules

Chemotherapy Cycles

Chemotherapy is typically given in cycles, with rest periods between the cycles.
A cycle can last 1 or more days.

A cycle is typically given every 1, 2, 3, or 4 weeks.

Each course of chemotherapy is different, but generally consists of four to six cycles.

It may take a relatively short period of time to receive some chemotherapy drugs, while others may take hours. It all depends on the treatment regimen that your doctor prescribes.
If your chemotherapy is given through an IV, your doctor may suggest an implanted vascular access device (VAD), such as an implanted catheter or port. VADs are surgically placed in a large vein near the heart and can stay in place for long periods of time. A VAD eliminates the need to have smaller catheters repeatedly placed in arm veins.

Chemotherapy Schedules

How often you receive chemotherapy depends on the type of cancer you have and the drug or combination of drugs you receive. Different drugs work at varying times in the cancer cell growth process. Taking all of these factors into consideration, your doctor will help you determine the most effective treatment schedule for you. Chemotherapy may also be used in combination with surgery.
Chemotherapy given before surgery is referred to as neoadjuvant chemotherapy. The goal of neoadjuvant chemotherapy is to shrink the cancer before it is surgically removed.

Chemotherapy after surgery is referred to as adjuvant chemotherapy. The goal of adjuvant chemotherapy is to kill any cancer cells left in the body after surgery.
Chemotherapy side effects can interfere with treatment schedules. To get the most from your treatment, learn how to best manage chemotherapy side effects.