Understanding Chemotherapy and Its Side Effects

Chemotherapy is a way of life for millions of cancer patients in the United States and world wide. While not necessarily a cure for cancer, it is one of the standard treatments along with surgery or radiation therapy depending on the type of cancer and location. Thanks to clinical trials, the chemotherapeutic agents used in recent years being with them a higher remission rate than ever before.

Chemotherapy, also called cytotoxic therapy, is systemic drug treatment, which can reach cancer cells that may have spread throughout the body. In some situations, chemotherapy can be administered into a specific area of the body to concentrate the effect. This approach to chemotherapy is called regional chemotherapy.

If high enough doses cannot be achieved to kill cancer cells, systemic and regional chemotherapy, including surgery, radiation therapy and/or intrathecal chemotherapy, may be used together.

Classification of Chemotherapy

A number of different types of chemotheraputic agents have been developed to kill cancer cells. The drugs are classified according to how they work.

Examples of the most common classes are alkylating agents (such as cyclophosphamide), antitumor antibiotics (such as doxorubicin), antimetabolites (such as methotrexate or fluorouracil [5-FU]), plant alkaloids (such as vincristine or paclitaxel), topoisomerase inhibitors (such as irinotecan) and miscellaneous agents that do not fit into these broad classes (such as L-asparaginase). (ONS 2006)

Chemotherapy regimens usually combine drugs from different classes so that the cancer cells are attacked by drugs with different mechanisms of action, thus increasing effect and decreasing resistance, and the drugs have different side effect profiles without overlapping toxicity in the same organ system (Barton-Burke & Wilkes 2003).

How Does Chemotherapy Work?

How the chemotherapy drug causes damage to the cell depends on the chemotherapy agent. Many of the drugs are directed at DNA, the carrier of genetic material, however the specific mechanism for how chemotherapy works to kill cancer depends on the type of agent. For example, an antimetabolite may interfere with cell division by inhibiting the DNA synthesis in the nucleus of the cell. An alkylating agent, such as cyclophosphamide, may cause damage to the DNA strands, which ultimately results in cell death.

Normal cells have a life span, and at some point they undergo what is called apoptosis, cell death, or cell suicide. Previously, it was thought that cancer cells may have a defect in the process of apoptosis and, therefore, do not undergo programmed cell death. (ONS 2006) It is now thought that chemotherapy causes damage in the cancer cell, which triggers cell death. Programmed cell death is actually cell disintegration.

Although the goal of chemotherapy is to increase the cancer cell kill throughout the body, the drugs often are not specific to just cancer cells. Consequently, damage can occur in many normal cells of the body and to a variety of different types of tissues.

Chemotherapy Side Effects

Some of the broad categories of side effects associated with chemotherapy are bone marrow suppression, nausea/vomiting, mucositis, hair loss or alopecia, liver toxicity, skin toxicity, lung toxicity, neurotoxicity, cardiotoxicity, hypersensitivity, renal toxicity, bladder toxicity, sexual dysfunction, infertility and secondary cancers. (Itano & Taoka 2005) The specific side effects depend upon the drug or drug combination, the dose, and the schedule of administration of the drug.

Chemotherapy-Induced Bone Marrow Suppression

One of the most common side effects of chemotherapy is bone marrow suppression, or a decrease in the production of the blood cells. The bone marrow is the area inside of bones where blood cells are made. The blood cells include platelets, red blood cells (RBCs), and white blood cells (WBCs).

Platelets are the cells that help blood to clot. When the production of platelets is decreased, patients tend to bruise and bleed easily.

RBCs carry oxygen throughout the body. A decrease in production of RBCs means that oxygen is not efficiently delivered to all tissues of the body.

WBCs help to protect the body. This group of cells is important in fighting infections and protecting the body from foreign "invaders." The WBCs help to coordinate the function of the immune system and a decreased number of WBCs results in an increased risk of infection. The three main groups of WBCs are Lymphocytes (B and T subtypes). Monocytes. Granulocytes.
Chemotherapy Induced Neutropenia

After chemotherapy, if the drug(s) cause bone marrow suppression, there is a decrease in the percentage of each of the types of blood cells. When the blood counts are at their lowest, it is called the nadir. When the number of neutrophils is decreased, it is called neutropenia. At this time, there is a serious risk of infection that can be life-threatening.

Chemotherapy-Induced Anemia

Anemia is a decrease in the number of RBCs. Anemia can be caused by many things including chemotherapy. The risk for anemia is dependent upon a number of chemotherapy and non-therapy-related factors.

Certain cancer therapies have an increased risk for anemia (such as high-dose chemotherapy). Concurrent therapy such as radiation and/or surgery can increase the risk for anemia. Elderly patients are at increased risk for anemia. Patients with poor nutritional status are also at increased risk for anemia.

The signs and symptoms of anemia are related to the reduced oxygen being delivered to the body's tissues. Symptoms include fatigue, poor concentration, shortness of breath, cold intolerance, increased heart rate, headache and dizziness.

Recently, the problem of fatigue that occurs with chemotherapy-related anemia has received increased attention. Patients report that this is one of the most debilitating side effects of chemotherapy. Luckily a drug called Neupogen can be given intravenously to help create new RBCs, and help patients bounce back quicker from anemia.

Management of Nausea and Vomiting

Nausea and vomiting are two of the most common and feared side effects of chemotherapy. Vomiting is also called "emesis."

A number of problems can result from uncontrolled nausea and/or vomiting including the inability to eat or drink, severe fatigue, patient discomfort, dehydration, changes in the body's electrolyte balance due to losses from vomiting, fear about receiving further chemotherapy, fractures from severe vomiting in patients with bone involvement and aspiration, or inhaling vomitus into the lungs.

Since nausea and vomiting can be caused by many factors, many different approaches can be used to treat it. The best approach is often a collaborative approach, using management strategies from several areas including medications, emotional support, dietary changes, and patient involvement and education.

It is easier to prevent chemotherapy-induced nausea and vomiting using medications, than to try to stop it after it begins. If you are too late, stopping nausea and vomiting will be almost impossible in many individuals and cause psychological stress and anticipation in future rounds of chemotherapy.

Psychosocial interventions are also very important to consider regarding nausea and vomiting. If the patient has had anticipatory nausea and/or vomiting (similar to nerves from a previous bad experience), behavioral therapies may be very helpful, such as relaxation, hypnosis, music, and art therapy. Healthcare professionals who specialize in these areas can be excellent referral resources.

Other helpful strategies include receiving emotional support from friends and loved ones, receiving treatment in a quiet and dimly lit area, modifying your diet to small, frequent bland meals and patient and family education.

The antiemetic medications should be given for the entire time that the patient might have nausea and vomiting. This time is determined by how quickly the chemotherapy drug(s) is/are excreted from the body. For example, if the patient may have nausea and vomiting starting on day 1 and continuing through day 3, it is important to ensure the medications also continue past day 3 or 4.

There are four types of nausea and vomiting:

1. Acute: occurs within the first 24 hours after receiving chemotherapy. Antiemetic drugs can be given orally or by the IV route. Both are equally effective in preventing nausea and vomiting if given at the right time.

2. Delayed: occurs 24 hours or more after receiving chemotherapy. The mechanism for delayed nausea is different than that of acute nausea and vomiting and sometimes can be undermanaged by your oncology team.

3. Breakthrough: occurs despite use of acute and/or delayed antiemetic medication.

4. Anticipatory: a conditioned response to the sights, sounds or smells remembered from past experiences of nausea or vomiting.

If the cause of the nausea and vomiting is found to be disease-related and not specifically chemotherapy related, preventative maintenance will not be effective and may be a sign of disease involvement and should be evaluated further.

Risk Factors for Nausea and Vomiting

Fishman and Mrozek-Orlowski (1999) identified the following risk factors for nausea and vomiting:

1. Women experience more nausea and vomiting than men.

2. Younger patients experience more nausea and vomiting than older patients.

3. Prior history of chronic, heavy alcohol use reduces risk; drug use; poor control of emesis in the past; or susceptibility to motion sickness increases risk.

4. Anxiety, pain, dehydration, and previous experiences may influence the occurrence and severity of nausea and vomiting.

5. Disease-related causes include bowel obstruction from tumor in or around the gastrointestinal tract, distended stomach, infection, poor liver or kidney function, and having a brain tumor.

6. Medications taken for other reasons (such as pain medications and antibiotics) also may contribute to nausea and vomiting.

Chemotherapy-Induced Mucositis

The cells lining the gastrointestinal tract divide frequently and thus are sensitive to the effects of chemotherapy. Mucositis is an inflammation of the gastrointestinal mucosa or lining, and is characterized by red, inflamed and eventually painful ulcerated tissues, local infection and the inability to eat, drink or take medications due to painful swallowing. Mucositis can occur throughout the gastrointestinal tract but when it occurs in the mouth, it is called stomatitis. (Itano & Taoka 2005)

Chemotherapy-Induced Alopecia

Some drugs cause hair loss, or alopecia. This can vary from hair thinning to complete and total hair loss. Scalp hair is very susceptible to the effects of chemotherapy. Hair loss usually starts approximately 7-10 days after starting chemotherapy. (Itano & Taoka 2005) Whether it occurs at all and the severity of the hair loss depends upon the drug, dose, and schedule. Hair loss usually is reversible, although the hair may be different in color and texture when it grows back. As the hair loss occurs, the scalp may be very sensitive to touch, and even painful. (ONS 2006)

Body hair is not as susceptible to the effects of chemotherapy, although the hair may thin. In some cases, total body hair may be lost.

Although alopecia may seem like a minor side effect, it is one that may constantly remind a patient that she or he has cancer. The importance or impact of alopecia should be determined as it can greatly affect body image.

Chemotherapy-Induced Neurotoxicity

Certain chemotherapy agents may cause damage to the nervous system. This damage may be temporary and reversible or permanent. When the damage is reversible, it may take time to see a return to the baseline functional state.

Neurotoxicity can be manifested in a number of ways:

Damage to the central nervous system means that there is damage to the brain or spinal cord. For example, cytarabine can cause cerebellar toxicity, or damage to the cerebellum, which is responsible for balance. (ONS 2006) The patient may be dizzy or unsteady on his or her feet.

Damage to the peripheral nervous system means that the nerves bringing information from the periphery to and from the spinal cord are damaged. For example, the drug paclitaxel causes peripheral neuropathy that results in numbness and pain in the hands and feet. (ONS 2006) If the neurotoxicity is severe, a patient may not be able to use his or her hands for fine motor activities like sewing or using tools.

Chemotherapy-Induced Cardiotoxicity

Some chemotherapy agents are toxic to the heart, which is called "cardiotoxicity." One of the most important types of cardiotoxicity occurs when chemotherapy damages the muscle of the heart. This causes the heart to be less efficient when pumping blood throughout the body. Toxicity of the heart muscle usually is seen with high cumulative drug doses. (ONS 2006)
This toxicity is similar in presentation to congestive heart failure. When the heart is unable to pump blood to all necessary tissues, oxygen is not delivered to the tissues of the body and the heart can become enlarged. The patient may experience symptoms related to the decrease of oxygen, such as shortness of breath or fatigue with activity.

In addition, some chemotherapy agents (or the solutions the drugs are prepared in), may cause acute changes in the heart rate or rhythm. While this needs special attention, it is not always a sign of chemotherapy-induced heart failure.

Chemotherapy Hypersensitivity

Chemotherapy, or the preparations used to administer chemotherapy, may cause allergic reactions referred to as hypersensitivity reactions. In fact, hypersensitivity reactions can occur with any medication. These reactions range from a rash to a major emergency, and may present as redness, rash, shortness of breath, or the sensation of throat swelling. (Itano & Taoka 2005)

To protect patient safety, patients receiving drugs known to have a high incidence of hypersensitivity reactions are closely monitored during the time of administration, and patients should be taught the potential risks and to notify a member of his or her healthcare team immediately if a reaction occurs. (ONS 2006)

Chemotherapy-Induced Renal Toxicity

Damage to the kidneys is referred to as renal toxicity. Certain chemotherapy agents can cause temporary or permanent damage to the kidneys. Renal toxicity can manifest in several ways, depending upon the chemotherapy agent.

Precipitation of the drug in the kidneys is one type of renal toxicity, causing a clogging of the system similar to a clogged sink. To prevent this toxicity, patients may be given fluids to ensure that the drug product stays in solution. Direct damage to the kidney by the drug is like damage to a toilet's plumbing in that the patient will be unable to regulate the elimination of fluid and electrolytes. Besides from this toxicity, immense pain is felt when kidneys are backed up as they begin to swell or become otherwise infected.

A lot of information comes with the term chemotherapy, sometimes too much for a sick individual to take in at once if at all. If the patient is unable to absorb some or all of this information, it is important for the caregiver or family members to have a basic understanding of chemotherapy and its side effects, that way, the caregiver will be better prepared to face and combat side effects and answer questions for the patient if they come up. The patient's oncology team is number one in chemotherapy education, but it doesn't hurt to go the extra mile and learn what you or your loved one is up against.

Sources:

The Cancer Basics Course (2006); Oncology Nursing Society (ONS).

Joanne Itano & Karen N. Taoka (2005); Core Curriculum for Oncology Nursing; 4th edition. Missouri: Saunders.

Margaret Barton-Burke & Gail M. Wilkes (2006); Cancer Therapies. Maine: Jones and Bartlett.

Fishman M & Mrozek-Orlowski M (1999) Cancer Chemotherapy Guidelines and Recommendations for Practice. 2nd ed. Pittsburgh: Oncology Nursing Press.