Chemotherapy Complications

Nurses can educate patients on expectations and possible prevention of symptoms.

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Learning Scope #422
1 contact hour
Expires Feb. 25, 2015

You can earn 1 contact hour of continuing education credit in three ways: 1) Grade and certificate are available immediately after taking the online test. 2) Send the answer sheet (or a photocopy) to ADVANCE for Nurses, Learning Scope, 2900 Horizon Dr., King of Prussia, PA 19406. 3) Fax the answer sheet to 610-278-1426. If faxing or mailing, allow 30 days to receive certificate or notice of failure. A certificate of credit will be awarded to participants who achieve a passing grade of 70% or better.

Merion Matters is an approved provider of continuing nursing education by the Pennsylvania State Nurses Association (No. 221-3-O-09), an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation.

Merion Matters is also approved as a provider by the California Board of Registered Nursing (No. 13230) and by the Florida Board of Nursing (No. 3298).

The goal of this continuing education offering is to provide nurses with current information on chemotherapy complications. After reading this article, you will be able to:

1. Describe the major classes of chemotherapy drugs and how they affect the cells.

2. Explain the difference between chemotherapy and biologic/targeted therapy.

3. Describe the most common side effects associated with chemotherapy.

  • The author has completed a disclosure form and reports no relationships relevant to the content of this article.

Many patients receive chemotherapy during treatment for cancer. However, chemotherapy cannot differentiate between cancer cells and normal cells in the human body. Replicating cells are injured more readily and provide the basis of the complications related to chemotherapy treatment. The intent of chemotherapy treatment is to balance the damage to normal cells with the destruction of cancer cells to meet the goal of preventing the reproduction, invasion or spread of cancer. Most chemotherapy agents are given for a variety of cancer diagnoses in many combinations.

This article will break down the major classifications of chemotherapy and outline, at an introductory level, the most common complications experienced by the patient receiving treatment. When side effects are known, the nurse can be more prepared to educate the patient on expectations as well as possible prevention of symptoms. Nurses also can conduct ongoing assessments of known side effects to determine how the patient is tolerating the prescribed treatment regimen.

Major Drug Classes

The normal cells in the body divide to replace injured or lost tissue as well as to develop normal tissue.1 The cells dividing more rapidly will be the most susceptible to damage from chemotherapy. Normal cells can repair themselves more readily than cancer cells, so the effects are generally acute but can be long term. The different regimens typically include several classes of chemotherapy to decrease the side effects while targeting cancer cells at different stages in the cell cycle.

The major classifications of chemotherapeutic drugs are alkylating agents, nitrosoureas, antimetabolites, antitumor antibiotics, mitotic inhibitors, miscellaneous agents and hormones. Newer agents include biologics and targeted therapies. Chemotherapy drugs are classified by their pharmacological properties as well as if they are cell cycle specific, non-specific or hormone.

Cell cycle specific drugs exert effects at a particular point in the division and replication of the cell. Generally, the cell cycle specific drugs are administered in frequent divided doses or in a continuous infusion over several hours or days to improve the chance of finding the cancer cell at a particular stage in the cycle. Cell cycle non-specific drugs can be effective at any stage of a cell cycle, including the resting phase, and are typically administered in larger less frequent doses.2

Alkylating Agents/Nitrosourea

The action of an alkylating agent is the substitution of an alkyl group for a hydrogen ion in the cell that results in single and double strand breaks in DNA as well as inhibiting the DNA strand from separating during any phase of the cell cycle.2

Alkylating agents can work on tumors that have slow or rapidly dividing cells. If the tumor divides slowly, the effects on the cancer can take longer due to slower replication followed by DNA damage and cell death.2 Nitrosoureas cross the blood brain barrier so they are frequently used in central nervous system and brain tumors.3

Nitrogen mustard was first used in World War I as chemical warfare. Many soldiers that had exposure during the war developed bone marrow suppression, which led to further examination of the drug's effects. The antineoplastic effect was finally identified after years of investigation during World War II.1

The general class side effects for alkylating agents include bone marrow suppression, nausea and vomiting, neuropathies, ototoxicity and nephrotoxicity. Nitrosoureas commonly cause bone marrow suppression, nausea and vomiting, pulmonary, hepatic and renal damage several weeks to months after the drug is given.1 Also, alkylating agents have been linked to secondary cancers months to many years after the patient receives the drug.2

Antitumor Antibiotics

Antitumor antibiotics, also referred to as anthracyclines, are naturally occurring microbial byproducts that act on the cell cycle to prevent cell division or induce apoptosis by causing DNA strands to break, or inhibit replication. These drugs also can work by fitting between base pairs of DNA, leading to an inability to repair itself.2 The use of antitumor antibiotics was discovered useful in cancer care in the 1950s and has been prescribed since that time.

The general class side effects of antitumor antibiotics are bone marrow suppression, stomatitis, cardiotoxicity, nausea and vomiting, alopecia, hyperpigmentation, skin and nail bed changes, hypersensitivity reactions, diarrhea and electrolyte imbalances. Many of the drugs included in this drug class have lifetime dose limits, making it necessary to keep accurate records of administration to prevent long-lasting cardio and pulmonary toxicity.1

Several of the antibiotics are considered vesicants or irritants. Vesicants have the ability to cause blistering or tissue necrosis if the drug is administered outside the venous system. Irritants typically will cause aching, tightness and/or phlebitis but do not cause tissue necrosis if extravasation occurs.2

Miscellaneous Agents

The miscellaneous agent category contains a variety of drugs that work in several different ways and are more drug-specific. The mechanisms of action may include blocking maturation of cells, stopping synthesis or triggering a mechanism that results in cell death. The most common side effects include bone marrow suppression, gastrointestinal toxicity and hepatotoxicity.2

Antimetabolites

Antimetabolites interrupt the cell cycle by substituting itself during the attempt to synthesize (S phase) normal metabolites, so that replication and repair of DNA is inhibited. There are different subclasses of antimetabolites (i.e., folate analog, purine analog, urea and adenosine analogs) which characterize which metabolite it substitutes. Rapidly reproducing cells enter the S phase more frequently resulting in increased cell death.1

The general class side effects of antimetabolites depend on the metabolite it replaces, but all cause bone marrow suppression. Folate disruption can cause mucositis. The purine and adenosine analogs typically cause nausea and vomiting. Fluorinated pyrimidines cause nausea and vomiting, stomatitis, diarrhea, fever and fatigue.1

Mitotic Inhibitors

Plant alkaloids and taxanes are common mitotic inhibitors. The class description suggests that the drugs mostly work to prevent cell division in the mitotic (M) phase of the cell cycle, but they also can affect other phases. Most of these drugs are metabolized in the liver, so any liver dysfunction may make it necessary to dose reduce or further impair liver function.1 The components of this class come from naturally occurring alkaloids isolated from plant material or are composed of a synthetic compound that was initially from a plant source.2

Some resources identify topoisomerase inhibitors as a classification itself, while others group them with mitotic inhibitors. Topoisomerase I and II are enzymes responsible for allowing DNA to uncoil and recoil during DNA synthesis. Topoisomerase I inhibitors cause single strand breaks, and II inhibitors make double DNA strand breaks.2

The general class side effects of mitotic inhibitors are peripheral neuropathies, bone marrow suppression, gastrointestinal disorders, hypersensitivity reactions and hepatic impairment.1 Mitotic inhibitors continue to be investigated to determine the exact mechanism of cell damage so that the toxicities can be decreased.

Most recently, scientists have discovered the telomere is damaged due to prolonged mitotic arrest.4 The number of cell divisions are decreased when telomeres are damaged or shortened leading to eventual cell death.5 Telomeres are at the end of a chromosome and help distinguish the natural end of the chromosome. Telomeres also help keep the number of times a cell replicates in check. If a telomere is not present at the end, then it signals a break in the chromosome from cancer treatment leading to instability. The DNA strand either needs to be repaired or the cell dies.

Hormone

Some tumors are stimulated by naturally occurring hormones in the body, typically breast and prostate. Various treatments will alter the hormonal activity of estrogens and/or androgens and may be steroidal or non-steroidal. Men who take hormonal therapy generally develop gynecomastia, decreased libido, impotence and hot flashes. Women will most likely develop hot flashes, myalgias, fatigue and depression.6

Adrenocorticoids cause lysis of lymphoid cells, which makes steroids a treatment option in lymphatic leukemia, myeloma and malignant lymphomas. Steroids also have the ability to move cells out of the resting phase to a phase a cell cycle specific drug will affect. Typically, steroids are used in short-term intermittent therapy due to the side effects associated with long-term use.2

Biologics & Targeted Therapy

In the last several years, many new drugs have come onto the market that target tumors differently than traditional chemotherapy medication. Biological therapy's role is to help the body's natural immune system target cancer cells more effectively. These treatments stimulate the body to make more of a particular substance (known as cytokines) or they may be a synthetic version of the substance to block activity (known as monoclonal antibodies, tyrosine kinase inhibitors, proteasome inhibitors, immunomodulatory agents or vaccines).

A commonly used cytokine therapy involves stimulation of the hematological system in response to bone marrow suppression following chemotherapy or radiation treatment. The use of granulocyte colony-stimulating factors (G-CSF) has improved the ability of patients to receive chemotherapy treatments on time. The most common side effects of G-CSF are bone pain, headache, myalgia and arthralgias.

Other cytokines used less frequently include those that stimulate erythropoiesis and platelet production. Interferons and interleukins are immunomodulators that assist the immune response. Typically, these drugs lead to flu-like symptoms such as fever, chills, rigors and myalgias.2

Monoclonal antibodies target specific receptor, ligand or growth factors. The side effects are based on the particular receptor and if the receptor occurs on the body's normal cells. The antibodies can be conjugated or unconjugated. Conjugated antibodies have a toxic agent attached to it, and the toxic substance only will be delivered to the specified receptor. Unconjugated antibodies attach to a receptor and alert the immune system to attack the cell.2

Infection

Most chemotherapy drugs damage the bone marrow's ability to reproduce blood cells. Granulocytes are the most important white blood cell in determining the risk of infection and include neutrophils, basophils and eosinophils. The length of time and degree of neutrophil suppression reflect the risk for developing an infection following chemotherapy and is measured as the absolute neutrophil count. There is no significant risk for infection if the neutrophil count is above 1500/mm³ and severe risk if the count is less than 500/mm³.2

Patients are typically instructed on ways to prevent infection such as frequent handwashing and avoiding crowds, people known to be sick, children with recent live vaccinations, dental work and food buffets. It also is crucial patients contact the oncology team if they develop a fever greater than 100.5° F.

The National Comprehensive Cancer Network (NCCN) has specific guidelines for medical management of the patient with febrile neutropenia. If the patient is receiving a regimen that has a high risk for neutropenia development, a G-CSF often is prescribed to reduce the duration of chemotherapy-associated neutropenia.

Diarrhea

Diarrhea generally is defined as an increase in frequency and liquidity of stools. Chemotherapy-induced diarrhea occurs as the cells are damaged in the intestinal mucosa and typically occurs 24-96 hours following treatment.2 The mucosal damage leads to inefficient absorption of fluid and can result in excess fluid in the bowel.7

When the crypt cells stop reproducing, the protective layer in the intestine is reduced and the epithelial surface of the intestines becomes flattened. Inflammation and edema develop in the bowel wall, the epithelium loses the ability to function and the patient begins losing water, electrolytes, lactase and protein.7,8

The management of diarrhea includes prevention, diet modifications and medical management of the complications. Prevention of diarrhea may include probiotic supplementation, psyllium fiber supplements and glutamine supplementation. Diet modifications should include adequate hydration, at least three liters of non-carbonated fluid per day and a low-residue diet. Medical management involves medications to treat the diarrhea, rehydrating with intravenous fluids, replacement of electrolytes and the use of medication to treat pain and discomfort.8 If medical interventions do not manage the side effects, the patient may require a treatment break.

Nausea & Vomiting

Several substances lead to nausea and vomiting in the oncology patient: dopamine, serotonin, endorphin and a peptide neurotransmitter substance P. A majority of serotonin is located in the enterochromaffin cells in the epithelial lining of the gut and locally affects the rate of intestinal motility.

Anything that irritates the enterochromaffin cells increases the release of serotonin resulting in an increase of gut motility and increasing the amount of serotonin in the blood stream. The increased serotonin then activates the receptors in the chemoreceptor trigger zone in the brain, resulting in nausea and vomiting.9 The chemoreceptor trigger zone contains high concentrations of the substance P, endorphin and dopamine receptor, which can directly transmit impulses to the vomiting center in the medulla.2

Patient-related risk factors include history of past nausea, age less than 50 years, female, motion sickness, infection, constipation, abnormal electrolytes and anxiety.10 The pharmacologic treatment for chemotherapy-induced nausea and vomiting includes serotonin (5HT3) receptor antagonists, dopamine receptor antagonists, substance P/neurokinin-1 receptor antagonist, steroids and benzodiazepines.11 NCCN guidelines recommend administration of specific antiemetics based on the emetogenic potential of the prescribed treatment regimen for prevention and treatment of chemotherapy-induced nausea and vomiting.

If patients do not have adequate preventive treatment, they may go on to develop anticipatory nausea and vomiting. Anticipatory nausea and vomiting is difficult to manage and may be brought on by a thought, smell or sight of anything associated with chemotherapy treatment.7

Self-care measures include eating small, frequent meals with foods at cold or room temperature. Foods at warmer temperatures tend to emit odors more than colder foods. Patients should avoid favorite and disliked foods during episodes of nausea to prevent future food aversions as well as avoidance of foods that are fatty, spicy or salty.10 Patients also may find that taking anti-emetics prior to eating will allow them to eat with more ease.7

Update Knowledge Base

Many new treatment modalities currently are being used or in development to either enhance the effectiveness of current treatments or replace chemotherapy. However, with the development of targeted therapy, new toxicities need to be addressed.

The treatment for cancer is exciting and ever-changing. Nurses involved in any aspect of oncology care need to constantly update their knowledge base to provide the best possible care to the patient.

References
1. Levine A. Cancer Basics. Pittsburgh, PA: Oncology Nursing Society; 2010.
2. Wilkes GM, Barton-Burke M. Oncology Nursing Drug Handbook. Boston, MA: Jones and Bartlett; 2009.
3. Shields S. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 2009.
4. Hayashi MT, et al. (2012). A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nat Struct Mol Biol. 2012;19(4):387-394.
5. Eisenberg DTA An evolutionary review of human telomere biology: The thrifty telomere hypothesis and notes on potential adaptive paternal effects. Am J Hum Biol. 2011:23(2);149-167.
6. Wilkes GM Advanced Oncology Nursing Certification Review and Resource Manual. Pittsburgh, PA: Oncology Nursing Society; 2009.
7. Brown CG, ed. A Guide to Oncology Symptom Management. Pittsburgh, PA: Oncology Nurses Society; 2010.
8. National Cancer Institute. Gastrointestinal Complications. http://www.cancer.gov/cancertopics/pdq/supportivecare/gastrointestinalcomplications/HealthProfessional
9. deWit R, et al. (2005). Is there a pharmacological basis for differences in 5HT3 receptor antagonist efficacy in refractory patients? Cancer Chemother Pharmacol. 56(3),231-238.
10. Holland J. Manual for Radiation Oncology Nursing Practice and Education. Pittsburgh, PA: Oncology Nursing Society, 2005.
11. National Cancer Institute. Nausea and Vomiting. http://www.cancer.gov/cancertopics/pdq/supportivecare/nausea/HealthProfessional/AllPages/Print

Ingrid Bowser is an oncology nurse practitioner at Indiana University Health Goshen Center for Cancer Care, in Goshen.




 
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