About this course:
This course provides an overview of the various oral and intravenous (IV) cancer treatment modalities, including chemotherapy, targeted agents, biologic and immune-mediated therapies, hormonal treatments, and chemoprevention.
This course provides an overview of the various oral and intravenous (IV) cancer treatment modalities, including chemotherapy, targeted agents, biologic and immune-mediated therapies, hormonal treatments, and chemoprevention.
After this activity, learners will be prepared to:
understand the difference between normal and cancerous cell development
discuss primary and secondary cancer prevention strategies
identify differences between cytotoxic chemotherapy and other cancer treatments
understand the different routes by which cancer treatments may be administered and the teaching points for each route
demonstrate understanding of the basic principles of safe handling, personal protective equipment (PPE), administration, storage, and disposal of hazardous medications
describe how the immune system can be used to prevent, detect, and treat cancer
differentiate between the side effects of chemotherapy, targeted therapies, immune-based therapies, and hormonal therapies and their management strategies
understand the principles of chemoprevention and identify common chemo-preventative agents
Cancer is a cluster of malignant diseases characterized by uncontrollable, abnormal cell growth; the ability to invade surrounding tissue and lymph nodes; and metastasis (spread) to distant locations within the body. The term “cancer” has evolved over several decades as biological research has successfully enhanced the scientific understanding of cancer development and spread. However, cancer research remains profoundly driven toward answering the trillion-dollar question: how do we correct the abnormal mechanisms that occur at the cellular level to prevent, eradicate, and control disease? Scientific advancements and treatment breakthroughs have revolutionized how cancer is managed, leading to innovative fields such as precision (or personalized) medicine, developing targeted therapies and immunotherapy. Precision medicine uses the genomic profiling of a patient’s tumor to identify unique genetic mutations. This information allows healthcare providers (HCPs) to tailor cancer treatment to the patient’s tumor and select the most effective treatment. Targeted therapies block the growth and spread of cancer by interfering with specific genes, proteins, and blood vessels that allow cancer cells to replicate, grow, and spread. Immune-based therapies assist the immune system in identifying cancer cells and attacking them, as it would for any other infection, virus, or potential threat. Immunotherapy refers to medications like monoclonal antibodies, checkpoint inhibitors, cancer vaccines, and CAR T-cell therapy. Nevertheless, cytotoxic chemotherapy remains the most prevalent treatment option and is still considered the standard of care and first-line treatment for many cancers (Miliotou & Papadopoulou, 2018; Nettina, 2019; Yarbro et al., 2018).
The National Comprehensive Cancer Network (NCCN, 2022) is an alliance of leading cancer centers and experts devoted to cancer care, research, and education. Through rigorous clinical trial research, data compiled across institutions, and annual expert panel reviews, the NCCN provides evidence-based guidelines for cancer treatment according to cancer type, pathology, genetics, staging, inheritance patterns, and other specific features. These guidelines are widely utilized in cancer care and guide medical decision-making throughout each patient’s disease trajectory. Despite the tremendous scientific advancements in identifying more specific and highly effective cancer treatments, drug resistance is a significant barrier to finding a cure for cancer. As a result, how to cure this disease remains unclear and unrequited as the disease continues to expand worldwide (NCCN, n.d.; NCCN, 2022; Yarbro et al., 2018).
According to the American Cancer Society (ACS, 2022), more than 1.9 million new cancer diagnoses are expected in the US in 2022, with approximately 609,360 cancer-related deaths. These numbers translate to nearly 1,670 deaths per day. Cancer is the second most common cause of death in the US, exceeded only by heart disease. These cancer estimates are based on reported incidence and mortality through 2019; therefore, the impact of the COVID-19 pandemic on cancer diagnoses and deaths remains unknown. The pandemic has disrupted healthcare services, resulting in missed or delayed diagnosis and treatment for millions in the US. Nevertheless, substantial progress has been made in the last few decades, with cancer deaths dropping from 215 to 146 per 100,000 people. This reduction in death rates is attributable to advancements in early detection and treatment and a reduction in smoking rates. There are an estimated 16.9 million cancer survivors in the US, representing 5% of the population; this number is projected to increase to 26.1 million by 2040 (ACS, 2022).
Pathophysiology of Cancer
Cancer cells have distinct features compared to normal cells, such as their appearance under a microscope, growth, replication, and function. The cell cycle is a 5-stage process of cellular reproduction that occurs in both standard and cancerous cells. Gap 0 or G0 (quiescence) is the resting stage in which cells are temporarily out of the cell cycle. During this stage, all cellular activity continues except for reproduction. During Gap 1 or G1, ribonucleic acid (RNA) and protein synthesis occur. This stage is considered the gap between resting and DNA synthesis. Synthesis or S occurs when deoxyribonucleic acid (DNA) synthesis occurs, as cellular DNA is duplicated in preparation for division. Gap 2 or G2 encompasses further protein and RNA synthesis as the cell constructs the mitotic apparatus. Finally, Mitosis or M, involves cellular division (Yarbro et al., 2018). See Figure 1 for a depiction of the cell cycle.
When cancer cells collect in an area, they develop into a malignant (or cancerous) tumor. Normal, healthy cells reproduce in an organized, controlled, and orderly manner as they mature into cells that serve specific functions and have predetermined lifespans. They undergo apoptosis, or programmed cell death, to help the body rid itself of unneeded cells. They do not divide when space or nutrients are limited and do not spread to other parts of the body. In contrast, cancer cells are less specialized and exhibit dysplasia (disorganized growth) and hyperplasia (increased size; see Figure 2 below). They can evade apoptosis as they continue to divide and grow uncontrollably, even when space is crowded. Cancer cells initiate new growth at distant sites (metastasis) and manipulate normal cells to generate blood vessels (angiogenesis) to supply the tumor with the additional oxygen and nutrients needed to grow. Cancer cells can hide from and evade the immune system, preventing it from recognizing them as abnormal and eradicating them (Nettina, 2019; Norris, 2020; Yarbro et al., 2018).
All cancer is inherently genetic, as all cancer cells carry genetic mutations that lead to unregulated cell division and growth. However, it is critical to understand the distinction between genetic and inherited, as these terms are not synonymous. Inherited (or hereditary) cancer occurs when a damaged gene with a high cancer susceptibility is passed through generations within a family. In other words, a patient with hereditary cancer is born with a genetic mutation and genetic predisposition to develop cancer at some point in their lives. A classic example of this is the BRCA1 and BRCA2 genes, which produce tumor-suppressor proteins that help repair damaged DNA, ensuring proper stability and function of cellular genetic material. When either of these genes is mutated, DNA damage may not be adequately restored, leaving cells vulnerable to additional genetic alterations that can lead to cancer. Inherited mutations in BRCA1/2 genes substantially increase the risk of breast and ovarian cancers and are also associated with a heightened risk for several other cancers. A mutated BRCA1/2 gene can be inherited through a patient’s mother or father. Therefore, each child of a parent who carries the mutation has a 50% chance of inheriting the mutation. Despite the heightened media attention on inherited cancers and BRCA mutations following the 2013 New York Times op-ed spotlighting celebrity Angelina Jolie’s decision to have a preventative mastectomy after learning she carried the genetic mutation, most cancers are not inherited, and patients are often diagnosed without a family history (Liede et al., 2018; Nettina, 2019; Ring & Modesitt, 2018).
Metastases, secondary growths of primary cancer in another organ, occur after a cancerous cell detaches from the original tumor site, invades local tissue, and migrates through the lymphatics and blood vessels to another area. Over time, the cancerous cell replicates in the new area, creating a secondary tumor site. The four most common sites where cancers metastasize include the liver, lung, bone, and central nervous system. A common misconception among patients with metastatic cancer is that they have developed a secondary cancer type, so vigilant patient and family education is often required to ensure accurate understanding. For example, a patient with breast cancer who develops metastases in the liver does not have liver cancer. Instead, the patient’s breast cancer cells have traveled to the liver, reproduced in the liver, and created a tumor, leading to a diagnosis of metastatic breast cancer or breast cancer with metastasis to the liver (Nettina, 2019; Norris, 2020; Yarbro et al., 2018).
Risk and Protective Factors
While the definitive cause of cancer is not entirely understood, numerous factors increase the risk for the disease and are generally distributed between 2 categories: modifiable and nonmodifiable. Some theories postulate that cancer may occasionally occur due to spontaneous cell transformation when no causative agent is identified. Still, most researchers view cancer development as a process resulting from cell damage induced by outside influences, called carcinogens.Carcinogens are substances, radiation, or exposures that can damage the genetic material (DNA) throughout a person’s lifetime, resulting in carcinogenesis or cancer formation. A few examples of carcinogens include tobacco, diesel exhaust, and ultraviolet radiation. Age is the most outstanding risk factor for cancer, as cancer incidence rises alongside age. Other risk factors include exposure to chemicals, viruses, poor nutrition, high-fat diets, obesity, sedentary lifestyles, and excessive alcohol intake (Nettina, 2019; Norris, 2020; Yarbro et al., 2018).
Many cancers can be thwarted through primary cancer prevention, which involves minimizing harmful exposures and reducing or avoiding unhealthy lifestyle behaviors. The ACS (2022) researchers have determined that approximately 42% of newly diagnosed cancers in the US are potentially avoidable, as they are directly correlated with tobacco use, obesity, a sedentary lifestyle, and other modifiable behaviors. Tobacco is the single most significant cause of cancer-related deaths and is attributed to more than 480,000 deaths annually, with 42,000 deaths from secondhand smoke. Skin cancers are primarily due to excessive sun exposure and indoor tanning beds. Prevention strategies should focus on applying proper sunscreen and wearing lightweight clothing and hats to shield oneself from direct exposure, reducing sunlight exposure during peak hours of the day when the ultraviolet rays are the strongest, and avoiding tanning beds altogether. Infections and viruses are associated with an increased risk of certain forms of cancer, such as the relationship between hepatitis B, hepatitis C, and hepatocellular cancer. Cancers related to human papillomavirus (HPV) can be prevented through behavioral and lifestyle changes and vaccination. According to the Centers for Disease Control and Prevention (CDC, 2021), more than 42 million Americans are currently infected with HPV strains that cause cancer, and approximately 13 million Americans become infected with HPV each year. HPV can cause cancers of the cervix, vagina, vulva, throat, tongue, and tonsils. In 2014, the US Food and Drug Administration (FDA) approved the HPV vaccination, Gardasil9, which can protect against over 90% of HPV cancers and genital warts (CDC, 2021; Nettina, 2019).
Secondary cancer prevention involves partaking in screenings and testing to identify high-risk individuals who require increased surveillance compared to the general population. These measures can prevent cancer by identifying precancerous lesions and taking appropriate action before the cells develop into invasive cancer or by undergoing interventions, such as prophylactic mastectomy in an otherwise healthy patient with a BRCA mutation to diminish the lifetime risk of breast cancer development. Screenings allow for early cancer detection when it is still treatable or potentially curable. Examples of cancer screening tests include colonoscopy, sigmoidoscopy, fecal occult blood testing (FOBT), mammography, Papanicolaou testing (pap smear), prostate-specific antigen (PSA), and digital rectal exam (DRE). Some institutions are now offering cancer screening programs with low-dose spiral computed tomography (CT) scans to detect curable stage I lung cancer in patients who meet designated criteria (Yarbro et al., 2018).
Goals of Cancer Therapy
Cancer therapy has four main goals: prevention, cure, control, and palliation. While prevention and cure are relatively transparent in their definitions, control refers to the extension of a patient’s life when a cure is unlikely or impossible by preventing the growth of new cancer cells and reducing the size and impact of the existing disease. Palliation focuses on comfort when cure and disease control cannot be achieved. Several key terms describe the types of therapy prescribed for cancer patients, important for nurses to understand. Neoadjuvant therapy is given to shrink a tumor so that the primary treatment, usually surgical intervention, may not need to be as extensive. For instance, in breast cancer patients, neoadjuvant chemotherapy is given to shrink the tumor so that the breast surgeon may be able to perform a lumpectomy instead of a mastectomy. Adjuvant therapy is given after the primary treatment and aims to prevent recurrence and reduce micro-metastases. For potentially curative treatment regimens, maximum tolerated doses of drugs are delivered on a specific schedule to achieve the greatest efficacy (i.e., highest cancer cell kill rate). Chemotherapy may also be used for palliation. Palliative therapy aims to relieve or delay cancer symptoms, focusing on comfort, symptom management, and improved quality of life. Therefore, with palliative intent, chemotherapy doses are often adjusted to minimize treatment-related toxicity. Chemoprevention uses certain pharmaceutical agents to prevent cancer in high-risk individuals. The most common example of chemoprevention is tamoxifen (Soltamox), an oral selective estrogen receptor modulator for women at high risk for the development of breast cancer. Myeloablation is the obliteration of bone marrow in preparation for stem cell or bone marrow transplantation with high-dose/intensive chemotherapy (Hinkle & Cheever, 2018; Norris, 2020; Yarbro et al., 2018).
Cancer can adapt and mutate over time, particularly in response to treatment. Drug resistance occurs when cancer stops responding to the prescribed treatment and starts to grow again. It poses a significant barrier to finding a cure for cancer, as tumors develop the ability to resist the effects of chemotherapy agents. For instance, a patient may have an initial robust response to treatment for some time, but then the treatment stops working. Drug failure in cancers attributed to resistance can have various causes, and multiple resistance mechanisms may occur. Intrinsic resistance occurs when cancer cells are inherently resistant to cancer drugs. In contrast, acquired resistance happens when cancer cells develop resistance after exposure to the drug due to the emergence of resistant cancer clones. In some cases, cancers can develop multiple drug resistance (MDR), resulting in minimal cell death and the growth of drug-resistant tumors. While there are several proposed rationales for cancer drug resistance, it is often due to a combination of issues (Konieczkowski et al., 2019; Wu et al., 2017; Yarbro et al., 2018). Some mechanisms include:
insufficient dosing leads to resistance caused by random mutations in cellular DNA
chemotherapy may kill sensitive cells and leave behind resistant cells to treatment
cells not killed by the chemotherapy mutate and become resistant to the drug
gene amplification (i.e., when a cancer cell produces hundreds of copies of a particular gene, which triggers an overproduction of protein rendering the drug ineffective)
drug efflux (i.e., when cancer cells pump the drug out of the cell as fast as it is going in using a molecule called p-glycoprotein)
blocking the protein that transports the drug across the cancer cell wall
cancer cells learning how to repair the DNA breaks caused by some cancer drugs
cancer cells developing a mechanism that inactivates the drug (Konieczkowski et al., 2019; Wu et al., 2017; Yarbro et al., 2018)
Concern for drug resistance is the primary reason cancer drugs are often given in combination. Since cancer cells are selective in their division, replication, and spread mechanisms, combining therapies with varying mechanisms of action can reduce the incidence of developing resistance to a single drug. Furthermore, as cancer progresses, it increasingly develops mutations. As a result, if cancer becomes resistant to a drug or a group of drugs, it is much more likely to become resistant to other drugs. Therefore, following appropriate evidence-based treatment guidelines is essential, as the best possible treatment protocol should be administered first (Konieczkowski et al., 2019; Wu et al., 2017; Yarbro et al., 2018).
Types of Therapies
Chemotherapy, also referred to as cytotoxic or antineoplastic therapy, encompasses a group of high-risk, hazardous drugs that destroy cancer cells with as few effects on healthy cells as possible. Chemotherapy generally works by interfering with the normal cell cycle, impairing DNA synthesis and cell replication, and preventing cancer cells from dividing, multiplying, and forming new cancer cells. The growth and size of a tumor are a product of the proportion of cells actively dividing (growth fraction), the length of the cell cycle (doubling time), and the rate of cell loss. The higher the growth fraction is, the greater the chemotherapy response or cell kill. Cancers with smaller tumor burdens are usually more sensitive to chemotherapy because they are vascular. As a tumor increases in size, the growth rate slows due to the crowding of cells, poor vascularization from decreased blood flow, and limited nutrients. As a result, the number of cells actively dying decreases, and treatments become less effective. Factors outside the characteristics of the tumor that influence response to chemotherapy include the patient’s general state of health and physical status, including performance status, comorbidities, age, and prior cancer treatment. Generally, chemotherapy-naïve patients (i.e., those who have never received chemotherapy before) tend to tolerate and respond to treatment with less toxicity and greater efficacy than those who have received prior therapies (Nettina, 2019; Yarbro et al., 2018).
Chemotherapy drugs are distributed throughout the body by the bloodstream and can cause significant morbidity and mortality if not used correctly and cautiously. Chemotherapy may be used as a single agent or in combination with other drugs. However, it is more commonly used in combination for greater efficacy against cancer and to reduce the potential for drug resistance. Most chemotherapy dosing is based on the patient’s body surface area (mg/m2). Other agents are based on the area under the curve (AUC), which refers to the amount of drug exposure or the total drug concentration in plasma over time. While the most common route of chemotherapy administration is IV, it may also be administered via other routes, including oral, subcutaneous (injection), intramuscular (injection), intrathecal (directly into the central nervous system), intravesicular (directly into the bladder by urinary catheter), or intraperitoneal (infused directly into the intraabdominal cavity). Intravenous chemotherapy is generally administered in hospitals, outpatient infusion clinics, or via continuous infusion pumps that patients wear at home (Amjad et al., 2022; Hinkle & Cheever, 2018; Konieczkowski et al., 2019).
Specialized education, preparation, and training are required for oncology nurses who administer chemotherapy and other hazardous cancer medications to ensure safe care for patients. The Oncology Nursing Society (ONS) offers the ONS/ONCC Immunotherapy Certificate Course and provides up-to-date, evidence-based resources. The ONS also outlines competencies required for nurses to administer these agents, including in-depth knowledge of cancer medications and infusion therapy practices. Most American accredited cancer centers and hospitals require oncology nurses to hold proper certification before administering these medications (ONS, n.d.-b). In addition, the American Society of Clinical Oncology's (ASCO) Quality Oncology Practice Initiative (QOPI) certification program also requires hospitals, infusion centers, and physician practices to comply with safety standards for chemotherapy administration (ASCO, n.d.; Nettina, 2019; Neuss et al., 2017).
Due to the ability of chemotherapy to cause severe irritation, damage, and injury to the veins and subcutaneous tissue, many patients have a central venous catheter (i.e., port or mediport) placed; this small device is surgically implanted under the skin, usually in the chest wall, for easy access to the bloodstream. The port may be used to draw blood and infuse chemotherapy drugs. Some chemotherapy medications, such as vesicants, can only be given through a port as they are too caustic to be given through a peripheral vein. Vesicants are drugs that can lead to severe soft tissue necrosis or the formation of blisters when they leak or infuse outside the vein and into the soft tissue (i.e., extravasation). Chemotherapy extravasation is manifested by a range of symptoms, and the severity varies according to the type, amount, and concentration of the drug. Initial symptoms can involve acute burning pain and swelling at the infusion site and become increasingly severe in the hours, days, and weeks following the initial injury. Patients may develop blisters, which usually begin within 3 to 5 days and may be followed by peeling or sloughing of the skin with invasion to and destruction of deeper structures. Tissue necrosis usually occurs within 2 to 3 weeks. In the most severe cases, damage can reach tendons, nerves, and joints, leading to functional and sensory impairment of the area, disfigurement, or loss of the limb entirely. Some examples of chemotherapy vesicants include doxorubicin (Doxil), dactinomycin (Cosmegen), mitomycin C (Mutamycin, Mitosol), and vinca alkaloids (Vinblastine, Vincristine, and Vinorelbine). For patients who receive chemotherapy through a peripheral IV site, nurses must remain hypervigilant to the appearance and function of the IV site before, during, and after the infusion, monitoring for erythema, swelling, and loss of blood return. Nurses should counsel patients to report any pain, burning, or other abnormal sensations during the infusion. Specific guidelines address the management of peripheral IV sites for chemotherapy, such as location, placement, monitoring parameters, and frequency of evaluations of blood return. All chemotherapy agents should be considered irritants, as they all can cause inflammation, pain, and/or irritation (Amjad et al., 2022; Hinkle & Cheever, 2018; Nettina, 2019; Olsen et al., 2019).
Most chemotherapeutic agents are broad in their attack, killing healthy cells along with cancer cells. According to Olsen and colleagues (2019), agents are classified according to their biochemical activity, mechanism of action, and phase of action during the cell cycle, which is broken into two major categories: cell cycle-specific and cell cycle-nonspecific. Cell cycle-specific drugs exert cytotoxic effects on cells actively dividing at targeted stages within the cell cycle. These drugs are not active against cancer cells during the resting phase (G0) and are schedule-dependent, meaning they are most effective if administered in divided doses or by continuous infusion. Continuous infusion may occur over 24 hours for up to 7 days and is primarily given at a slower rate, allowing the drug to reach more cancer cells when they are actively dividing and amenable to cell kill. In contrast, cell cycle-nonspecific drugs have a broader impact on cancer cells, as significant cytotoxic effects are exerted on cells at any phase within the cell cycle, including G0. These agents are considered dose-dependent and are most effective when administered by bolus, as the number of cells affected is directly proportional to the amount of drug given. Table 1 displays the classification of the most common chemotherapy agents according to their mechanism of action and effect on the cell cycle (Healy, 2022; Norris, 2020).
Since cancer cells divide rapidly, chemotherapy is primed to target rapidly dividing cells, impacting normal cells that divide quickly, such as the gastrointestinal tract, skin/hair cells, and bone marrow. Thus, the most common chemotherapy side effects include bone marrow suppression, nausea, vomiting, diarrhea, hair loss, and mucositis. Several chemotherapy agents have dose-limiting toxicities, which are defined by the occurrence of severe toxicities and side effects during systemic cancer therapy that is serious enough to reduce the dose or discontinue the treatment altogether. Dose-limiting toxicities require early recognition and intervention to minimize hospital admissions, readmissions, and infections and improve the patient’s survival. There is an extensive range of acute and long-term toxicities associated with chemotherapy agents. The comprehensive list extends well beyond the scope of this module; however, the most common side effects will be discussed. Refer to Table 2 for an overview of the most common side effects of various chemotherapy agents (Amjad et al., 2022; Hinkle & Cheever, 2018; Norris, 2020; Olsen et al., 2019).
Bone marrow suppression refers to 3 main hematopoietic consequences of chemotherapy: neutropenia (reduction in white blood cells [WBCs]), anemia (reduction in red blood cells), and thrombocytopenia (reduction in platelets). Patients are most likely to experience a chemotherapy nadir, where the blood counts are at their lowest, approximately 7-10 days after each chemotherapy dose. When the body’s natural immune defense is suppressed due to chemotherapy, the patient is considered neutropenic, and their ability to respond to everyday germs, bacteria, or pathogens is very poor. As a result, the patient is highly susceptible to acquiring illness and bloodstream infections (bacteremia or sepsis). Neutropenia is defined by an absolute neutrophil count (ANC) of 1,500/mm3 or below and is a primary dose-limiting toxicity of chemotherapy. The risk for infection is heightened when the ANC drops below 500/mm3. The most common sign of infection in a neutropenic patient is a fever, and patients need to be monitored and treated promptly for fevers or other signs of infection. Fever in the setting of neutropenia is called febrile neutropenia, which is a medical emergency requiring prompt evaluation and workup and the initiation of empiric antibiotics. Patients should be counseled on ways to avoid infection, such as thorough handwashing, hygiene, and avoiding those with illness. Patients should also avoid eating raw meats, seafood, and eggs as well as unwashed vegetables when neutropenic due to the risk of acquiring foodborne illness (DeVita et al., 2018; Nettina, 2019).
Some providers may prescribe a colony-stimulating factor such as filgrastim (Neupogen) or pegfilgrastim (Neulasta) to help manage neutropenia. These injectable agents stimulate the bone marrow to produce WBCs rapidly, thereby reducing the risk of infection and neutropenic fever. According to Olsen and colleagues (2019), there are specific parameters and indications for using a colony-stimulating agent, and these agents are usually well-tolerated. The most common side effects include bone pain, particularly in the long bones such as the hips and sternum, where bone marrow is naturally produced. Patients may use over-the-counter (OTC) pain relievers such as acetaminophen or nonsteroidal anti-inflammatory drugs for comfort; however, most patients find antihistamines provide superior relief from symptoms (Olsen et al., 2019).
Anemia is a common consequence of chemotherapy and generally becomes more significant with each successive dose of chemotherapy as patients progress through treatment. In addition to low hemoglobin and hematocrit, patients may display symptoms of pallor, fatigue, low energy, chest pain, shortness of breath (SOB), and weakness. Some patients may benefit from oral iron supplements, folic acid, and consuming an iron-rich diet. Others may require erythropoietin-stimulating agents such as epoetin alfa (Procrit, Epogen), darbepoetin alfa (Aranesp), or blood transfusions. Thrombocytopenia, or a low platelet count, is an effect of chemotherapy caused by the suppression of megakaryocytes in the blood, impairing the body’s ability to form a blood clot and heightening the risk of bleeding. Platelets stop bleeding by clumping and forming plaques in blood vessel injuries, such as cuts, lacerations, and other wounds. The risk of bleeding is present when a patient’s platelet count falls below 50,000/mm3, becomes a high risk if their count falls below 20,000/mm3, and becomes a critical risk if their count falls below 10,000/mm3. Patients may require platelet transfusions if their count drops below 20,000/mm3. This is particularly dangerous for patients on anticoagulation therapy, as their risk of bleeding is already increased, and they require close monitoring and surveillance. Signs of thrombocytopenia may include easy bruising, petechiae, epistaxis, gum bleeding, hematuria, rectal bleeding, wounds that will not stop bleeding, or any other acute signs of bleeding. It is critical to counsel patients regarding ways to prevent injury when their platelet counts are low, including avoiding shaving with razors, using rectal suppositories, using dental floss, or participating in activities that increase their risk of injury (e.g., contact sports, skiing, horseback riding). Patients and caregivers must also be counseled on the risk for hemorrhage, paying particular attention to any acute head injuries. Patients with low platelet counts involved in a motor vehicle collision (MVC) or any kind of trauma or fall in which they hit their head are at increased risk for subarachnoid or intracerebral hemorrhage or acute bleeding inside the skull. These patients always require emergent evaluation by a clinician and will often undergo radiographic imaging of the head to rule out bleeding, such as a CT scan (Brant, 2020; Nettina, 2019; Olsen et al., 2019).
The gastrointestinal (GI) system is routinely impacted by chemotherapy, causing side effects such as nausea, vomiting, diarrhea, constipation, anorexia, and mucositis. These symptoms can lead to serious complications such as dehydration (fluid volume deficit), electrolyte disturbances, protein deficit, weight loss, and cachexia (muscle wasting). Anorexia, or loss of appetite, usually has a multifactorial etiology in cancer patients receiving chemotherapy. Patients often endure dysgeusia, or absent or altered taste, as the chemotherapy changes the reproduction of taste buds. This can lead to inadequate nutrition and protein intake, resulting in weight loss and cancer-provoked cachexia. Mucositis refers to inflammation and ulceration of the mucous membranes lining the mouth and other parts of the GI tract. This condition commonly presents with initial oral burning and discomfort, followed by the disruption of open sores and ulcers throughout the oral cavity, extending down the GI tract to the anus. Mucositis can significantly impair oral intake due to the associated pain, thrush, and dysphagia (difficulty swallowing). Consistent oral hygiene with baking soda-based oral rinses and normal saline solution is critical for promoting healing, stimulating cell turnover, and avoiding infection. Patients should be encouraged to use oral agents to promote cleansing, debridement, and comfort, and alcohol-based mouthwashes should be avoided due to the potential for irritation. Painful mucositis can also be treated with oral solutions, including antifungal suspensions (i.e., nystatin) and lidocaine (numbing analgesia) for comfort. Nurses must monitor for diarrhea and constipation in patients on chemotherapy, as life-threatening diarrhea is associated with certain chemotherapeutic agents, particularly irinotecan (Camptosar). This drug has such a high risk of inducing severe diarrhea that it has been called “I ran to the can” by oncology nurses for decades. Diarrhea can be life-threatening due to associated fluid and electrolyte depletion, as electrolyte imbalance can induce changes in cardiac function. In contrast, constipation can exacerbate existing anorexia and nausea as well as place patients at risk for bowel obstructions. Nurses should assess and monitor patients for changes in bowel habits before each treatment (Brant, 2020; Nettina, 2019; Olsen et al., 2019).
According to DeVita and colleagues (2018), chemotherapy-induced nausea and vomiting patterns include acute, delayed, and anticipatory nausea. The researchers describe acute nausea as occurring 0 to 24 hours after chemotherapy administration, whereas delayed nausea often occurs several days after chemotherapy administration. Anticipatory nausea is a conditioned response generated from the repeated association between a treatment and prior nausea and vomiting episodes. It may even be triggered by entering the hospital environment, certain smells, or sounds. Anticipatory nausea can and should be prevented with adequate antiemetic control. Prevention of nausea and vomiting is the goal, so the prescribed nausea management plan is directly correlated with the level of emetogenicity of the drug (DeVita et al., 2018).
Each chemotherapeutic agent is classified according to its emetogenic (nausea-inducing) risk, ranked low to high. Several major oncology groups have published consensus reports and evidence-based guidelines on preventing chemotherapy-induced emesis, such as the NCCN, ONS, and ASCO. Highly emetogenic drugs require enhanced anti-emetic control with dual or triple therapy targeting various nausea receptors. Before starting any chemotherapy regimen, the nurse must thoroughly assess the patient’s prior experiences with nausea to tailor nursing interventions to meet their needs. Identifying factors that stimulated nausea in the past can help prevent anticipatory nausea and ease the patient's overall experience and outcome. All patients should be premedicated with an appropriate antiemetic and have prescribed as-needed antiemetic agents at home. The most common antiemetic medication regimens include first-generation serotonin receptor antagonists (i.e., ondansetron [Zofran]), an NK1 receptor antagonist (i.e., aprepitant [Emend]), and a first-generation antipsychotic (i.e., prochlorperazine [Compazine]). For severe nausea and vomiting uncontrolled by the prior options, many clinicians will add corticosteroids (i.e., dexamethasone [Decadron]) for enhanced control. Nurses must teach patients and families to respond quickly to breakthrough nausea with as-needed medications before vomiting occurs. Patients should also be counseled on the benefit of consuming small, frequent, high-calorie meals instead of trying to consume three large meals daily. For more evidence-based information, refer to ONS guidelines on controlling chemotherapy-induced nausea and vomiting (CINV) or NCCN guidelines for supportive care and antiemesis (ASCO, n.d.; DeVita et al., 2018; NCCN, 2022; ONS, n.d.-a).
Alopecia, or hair loss, deserves special attention because it can cause significant emotional distress to patients. Chemotherapy-induced hair loss generally begins as hair thinning about 7-15 days after the first dose. It is due to damage to the dividing hair matrix cells, which causes the hair shaft to break at the follicular orifice or hair bulb. The degree of hair loss depends on the chemotherapy agent, the dose, and the administration schedule. Not all chemotherapy agents cause hair loss, so it is possible to undergo chemotherapy treatment without losing hair. However, certain regimens cause complete hair loss, specifically first-line chemotherapy for breast cancer, ovarian cancer, and endometrial cancer. Some agents that cause complete alopecia include higher doses of cyclophosphamide (Cytoxan), paclitaxel (Taxol), bleomycin (Blenoxane), dactinomycin (Cosmegan), topotecan (Hycamtin), and docetaxel (Taxotere). In contrast, much less hair loss occurs with agents such as 5-fluorouracil (Adrucil), etoposide (Vepesid), gemcitabine (Gemzar), methotrexate (Trexall), and ifosfamide (Ifex). Patients should be counseled that their hair will begin to regrow within a few weeks following the cessation of chemotherapy, as permanent alopecia following chemotherapy is rare (Olsen et al., 2019).
Novel treatments such as scalp hypothermia (i.e., “cold caps” or “scalp cooling”) worn during the infusion of certain alopecia-inducing chemotherapies are effective in reducing alopecia (Rice et al., 2018). Gianotti and colleagues (2019) conducted a multicenter interventional study and found a 68% overall success rate of scalp cooling in preventing hair loss in women being treated for breast cancer. Severe hair loss was avoided in 89% of the women receiving taxane-based chemotherapy and 78% of women receiving both anthracyclines and taxanes. These researchers utilized cold caps and scalp cooling systems, which are tightly fitting, helmet-type hats filled with a gel coolant chilled to between -15 and -40 degrees Fahrenheit. According to Gianotti and colleagues (2019), scalp cooling works by narrowing the blood vessels beneath the skin of the scalp, reducing the amount of chemotherapy medicine that reaches the hair follicles. The cold is postulated to decrease the activity of the hair follicles, which slows cell division and makes the follicles less affected by the chemotherapy (Gianotti et al., 2019).
Chemotherapy-induced peripheral neuropathy (CIPN) can be a severe side effect commonly associated with specific agents such as the platinum agents (carboplatin [Paraplatin], oxaliplatin [Eloxatin]), the taxanes (Paclitaxel, Docetaxel), vinca alkaloids (vincristine [Oncovin], vinblastine [Velban]), thalidomide (Thalomid), and bortezomib (Velcade). CIPN results from injury to the sensory and motor axons due to demyelination, which reduces nerve conduction velocity, leading to the loss of deep tendon reflexes and symptoms of paresthesia (numbness and tingling), weakness, and burning pain. CIPN often initially affects the most distal points of the body, such as the fingertips and toes, and progressively moves up the extremities toward the midline. Symptoms are usually symmetrical, and, in severe cases, patients may lose sensation of the fingers, hands, toes, and feet altogether, leading to dysfunction in the ability to grasp or hold items and gait disturbance, including imbalance and falls. CIPN is a complex topic since no single unifying pathophysiologic process can be identified to explain the various neuropathies that occur after exposure to different chemotherapeutic agents. CIPN is dose-dependent and progressive during treatment but can also have a cascading effect after treatment ends, with symptoms becoming more prominent after discontinuation of the offending agent. Pain, sensory changes, and weakness present during treatment generally lead to chemotherapy dose reductions, changes in treatment protocols, or termination of the therapeutic agent entirely. The morbidity associated with CIPN can lead to pronounced alterations in quality of life and loss of independence with activities of daily living. Although its etiology is not well established or understood, CIPN can be severe, debilitating, and dose-limiting toxicity of certain chemotherapies (Brown et al., 2019).
Currently, no medications or supplements have been shown to prevent CIPN definitively. Exercising regularly, reducing alcohol use, and treating preexisting medical conditions (e.g., vitamin B12 deficiency) may reduce the risk of CIPN. Patients undergoing treatment with agents that cause neuropathy may be advised to take B vitamin supplementation prophylactically. However, research confirming the benefit of this intervention in reducing the risk of neuropathy is not available. Management of CIPN is equally complex, and effective treatment options are limited. Pharmacologic treatment focuses on symptom relief, even though many agents are not consistently effective. OTC pain medications, menthol creams, capsaicin cream, or lidocaine patches may be used for comfort. Some patients may be prescribed medications such as gabapentin (Neurontin), an anti-convulsant/anti-epileptic agent that is also utilized to treat neuropathic pain. Some patients may find relief from selective serotonin-norepinephrine reuptake inhibitors (SSRIs) such as duloxetine (Cymbalta). Patients with CIPN must be counseled on ways to avoid injury, such as wearing good, supportive, close-toed shoes and paying attention to home safety by using handrails on stairs and removing throw rugs. Patients must also be mindful of water temperatures as they may become less sensitive to hot water, increasing their risk of burns when bathing or washing dishes. Improvement in function and resolution of symptoms often occurs gradually over time, but in some cases, nerve damage may be permanent (Brown et al., 2019; Olsen et al., 2019).
Chemotherapy-induced cardiotoxicity is a serious complication that limits the use of certain chemotherapy agents due to the culmination of life-threatening dysrhythmias, conduction disturbances, cardiomyopathies, pericarditis or myocarditis, and pericardial effusions. Anthracyclines, including doxorubicin (Adriamycin), daunorubicin (Cerubidine), epirubicin (Ellence), and idarubicin (Idamycin), are some of the medications that most often induce cardiac effects. Acute cardiotoxicities that occur during treatment or immediately afterward are typically reversible and generally manageable; however, chronic cardiotoxicity may manifest for long periods, up to decades after the completion of treatment. Chronic cardiotoxicity is serious and clinically significant, substantially affecting overall morbidity and mortality and requiring long-term management. The cumulative dose of doxorubicin (Adriamycin) is an essential factor that dictates the potential for cardiotoxicity. The cumulative dose should not exceed 500 mg/m2, or the risk of congestive heart failure (CHF) will rise tremendously. Nurses must remain vigilant when administering cardiotoxic chemotherapy agents to ensure cumulative doses do not exceed 500 mg/m2. Patients should undergo baseline cardiac evaluation with an echocardiogram or a multigated acquisition (MUGA) scan to evaluate cardiac function and left ventricular ejection fraction (LVEF) before initiating cardiotoxic therapies, then again at defined intervals and as clinically indicated. Patients should also be monitored closely for any signs and symptoms of cardiac dysfunction such as dyspnea, peripheral edema, chest pain (angina), and lightheadedness. Early detection and immediate proper medication can reverse the condition in time, minimizing cardiotoxic effects (Olsen et al., 2019).
Chemotherapy may induce reproductive alterations in all genders, including sexual dysfunction, loss of libido, and psychological effects associated with distorted body image. For instance, surgical intervention with orchiectomy (removal of testis in males with testicular cancer) or mastectomy (removal of breasts in females with breast cancer) may negatively impact a patient’s self-image and, in turn, impair sexual health and intimate relationships. Side effects of chemotherapy can induce other body image distortions secondary to alopecia, vaginal dryness from hormonal therapy, and erectile dysfunction. For females, chemotherapy can cause amenorrhea (permanent or temporary loss of menses), damage the ovarian follicles, or cause ovarian fibrosis. It can also induce premature ovarian failure leading to infertility and menopause, with associated hot flashes, night sweats, and weight gain. Males may experience low sperm counts, poor sperm motility, sterility, impotence, and erectile dysfunction. Nurses have a responsibility to ensure patients are educated honestly and openly about the potential effects of chemotherapy, including the possibility of fertility loss. Patients or couples may desire fertility preservation for future family planning with cryopreservation of embryos or sperm (Brant, 2020; Liede et al., 2018).
Patients must be educated on safe sex practices while undergoing cancer treatment. Patients and their partners must understand the importance of taking precautions to avoid pregnancy while receiving treatment, as chemotherapy can induce fetal harm and congenital disabilities if the fetus is exposed during certain stages of development. Females must be educated that it is still possible to conceive despite not having regular menstrual cycles during chemotherapy, so proper precautions must be taken to avoid pregnancy during their treatment. Patients should be advised to abstain from sexual intercourse within the first 24-48 hours after chemotherapy due to the known presence of chemotherapy in bodily fluids. Patients should then use a barrier method, such as a condom, to prevent any unnecessary exposure to partners via bodily fluids. Finally, breastfeeding is contraindicated during chemotherapy treatment due to drug exposure in breastmilk (Brant, 2020; Olsen et al., 2019).
A hypersensitivity reaction (HSR) occurs when the immune system is overstimulated by a foreign substance (e.g., chemotherapy) and forms antibodies that cause an immune response. Some chemotherapeutic agents commonly associated with HSRs include paclitaxel (Taxol), L-asparaginase (Erwinaze), and bleomycin (Blenoxane). HSRs can occur during the initial chemotherapy infusion or after subsequent administrations of the same agent. Most HSRs occur during the first 15 minutes of the infusion, but reactions can happen outside of this time frame. Initial signs and symptoms can include hives, urticaria, pruritis, swelling, back pain, facial flushing, rhinitis, abdominal cramping, chills, and anxiety. However, symptoms may suddenly progress to life-threatening hypotension, bronchospasm, angioedema (swelling of the oral cavity, lips, or tongue), and anaphylaxis. In these cases, epinephrine 0.1-0.5 mg (1:10,000 solution for adult patients) may need to be administered by IV push or subcutaneous injection until emergency personnel arrives. The risk of HSRs can be reduced by pre-medicating patients with a combination of corticosteroids, antihistamines, acetaminophen, and H2-receptor antagonists. Oncology nurses must remain vigilant for signs of HSR and ensure they are prepared to intervene immediately. If an HSR is suspected, the nurse must first stop the infusion immediately, notify the HCP, and monitor the patient closely. Additional nursing interventions include monitoring vital signs, applying supplemental oxygen, and administering normal saline and other emergency medications as indicated per institution policy or physician order. Nurses should be familiar with their institution’s specific chemotherapy hypersensitivity protocols and policies for further information and instruction (Nettina, 2019).
Safety and Exposure
Cytotoxic drugs also can be hazardous to nurses and other healthcare workers, so it is critical to adhere to the standards of practice of hazardous drug handling to minimize occupational exposure. Exposure to hazardous medications is linked to increased risks for several types of malignancies, and exposure can occur through various sources, including workplace surface contamination. According to the 2016 updated ASCO and ONS chemotherapy administration safety standards as outlined by Neuss and colleagues (2017), nurses must wear appropriate PPE whenever there is a risk of chemotherapy being released into the environment, such as when preparing or mixing chemotherapy, spiking/priming IV tubing, administering the drug, and handling body fluids or chemotherapy spills. These guidelines also describe hazardous drug handling as posing reproductive risks, so healthcare workers who are pregnant, breastfeeding, or trying to conceive must notify their employer. These individuals should not be handling hazardous medications such as chemotherapy (Neuss et al., 2017; Olsen et al., 2019).
The guidelines indicate chemotherapy medications must be mixed, spiked, and primed under an approved filtered hood to reduce the risk of aerosolized exposure. Gloves tested for use with hazardous drugs are required, and reuse of gloves is prohibited. Nurses should wear disposable, lint-free gowns made of low-permeability fabric when administering chemotherapy, and spill kits should be available in all areas where chemotherapy is stored, prepared, and administered. Gloves and gowns should be discarded in leak-proof containers marked as contaminated or hazardous waste. Linens or clothes contaminated with chemotherapy or bodily fluids from patients who have received chemotherapy within 48 hours should be contained in specially marked hazardous waste bags. If any chemotherapy spills on clothes in the clinic, clothing should be thrown away or double-bagged in a plastic bag sealed for transport home. The clothing must be washed separately in hot water with regular detergent. The ONS has two standards that address the education of nurses who administer and care for patients receiving chemotherapy, biotherapy, and immunotherapy agents. The standards support RNs as the minimum appropriately licensed professionals who administer chemotherapy and biotherapy. They recommend educational requirements for nurses, regardless of treatment indications, clinical settings, routes of administration, and patient population. Due to the unique safety considerations of these drugs, specialized education is needed for all nurses who administer chemotherapy or other anti-cancer agents. The ONS offers online courses for initial didactic preparation and knowledge maintenance for nurses administering chemotherapy and immune-based treatments. However, each institution or practice must determine how to assess nursing competence in performing various chemotherapy-related skills (Neuss et al., 2017; Olsen et al., 2019; ONS, 2022).
Immunotherapy, or biologic therapy, is a relatively novel sector of cancer treatment that stimulates the body’s immune system to fight cancer. Immunotherapy has emerged as an important cancer treatment modality, and intensive research is being conducted. The connection between cancer and the immune system was discovered nearly 100 years ago by Dr. William Coley. He was deemed the father of immunotherapy after discovering malignant tumors disappear in patients who contracted acute streptococcal infections. The goal of immunotherapy is to produce antitumor effects through the action of natural host defense mechanisms. Since the immune system's primary function is to detect and eliminate any foreign pathogens, immunotherapy strives to modify the patient’s immune defenses to become more sensitive to cancer cells by learning how to identify, attack, and kill them to promote tumor regression. More recently, novel drugs known as checkpoint inhibitors have been developed to enable the immune system to harness disease-fighting immune cells (T-cells) against cancer more effectively. These are systemic treatments, and they work differently than chemotherapy as they are so specific in their action. Some forms of immunotherapy are so highly specialized that they only target a single receptor on the surface of tumor cells. Immunotherapies are frequently combined with other treatment modalities. The main types of immunotherapies currently being used to treat cancer include monoclonal antibodies, immune checkpoint inhibitors, and cancer vaccines. While immunotherapy represents a promising cancer treatment approach, it is still not equally effective for all cancers at this stage in development (Miliotou & Papadopoulou, 2018; Nettina, 2019; Sengupta, 2017; Yarbro et al., 2019).
Overview of the Immune System
The immune system is a collection of cells, tissues, and organs that work together to defend the body against attacks by “foreign” invaders such as microbes, viruses, parasites, or other pathogens. The immune system strives to prevent invasion and protect against illness and infection by seeking out and destroying pathogens. The key to a healthy immune system is its ability to distinguish between the body’s cells (“self”) and foreign cells (“non-self”). The immune system cells launch an attack when they encounter anything that appears foreign. Any substance capable of triggering an immune response is called an antigen. An antigen can be a microbe, such as a virus or bacteria, and all antigens carry marker molecules that identify them as foreign. The organs of the immune system are positioned throughout the body. They are called lymphoid organs because they house lymphocytes, the small WBCs that are the key performers of the adaptive immune system. There are two main types of lymphocytes: B-cells and T-cells. B-cells work by secreting substances called antibodies into the body’s fluids, which ambush antigens circulating in the bloodstream. They then hand the baton to the T-cells, which attack the target cells (the infected cells). An antigen matches an antibody, much like a key matches a lock (Miliotou & Papadopoulou, 2018).
Mounting an Immune Response
There are two main types of immune responses: innate (or nonspecific) and acquired (or adaptive) immunity. Innate immunity is also known as natural immunity, as it is present from birth. It is considered the first line of defense against pathogens and is a nonspecific form of immunity that is activated immediately and rapidly in response to invading pathogens. Innate immunity is always present in the body, prepared to attack predators, and does not generate immunologic memory. In other words, the innate immune system has no memory of prior predators and responds nonspecifically to each attack. It includes physical barriers (skin and mucous membranes), mechanical barriers (coughing and sneezing), chemical barriers (tears and sweat), inflammatory responses (production of specialized WBCs such as neutrophils, macrophages, and monocytes), complement activation, and the production of natural killer (NK) cells (large granular lymphocytes). An example of innate immunity includes the development of redness and swelling around a wound caused by lymphocytes invading the wound, working to keep microbes out and heal the injury before further damage or infection occurs (DeVita et al., 2018; Nettina, 2019).
Adaptive immunity is the second line of defense and is highly specific, as it responds individually to every pathogen. Mediated by T-cells and B-cells, the adaptive immune system responds if invading pathogens breach innate immune mechanisms. The adaptive immune system has immunologic memory and specificity, meaning it “remembers” prior attacks and can develop a repeat specified response. An example of adaptive immunity is a vaccination, which leads to the creation of antibodies against a virus to prevent the acquisition of the illness later. If that virus tries to invade the body, the adaptive immune system is activated to produce additional antibodies quickly to address the infection and prevent illness. The acquired immune system responds comparatively slower than the innate immune system. There are three types of adaptive immunity: humoral immunity, cell-mediated immunity, and T-regulatory cells. Humoral immunity is mediated primarily by B-cells and results in the production of immunoglobulins (IGs). Cell-mediated immunity is mediated by T-cells and their cytokine products. It does not involve an antibody but instead includes cytotoxic T-cells (usually CD8) and helper T-cells (usually CD4). T-regulatory cells, also known as suppressor T-cells, display the markers CD4 and CD25 and limit the activity of other immune effector cells. Ultimately, their primary role is to prevent damage to normal tissues and limit the inflammatory response that can occur with infections (DeVita et al., 2018; Nettina, 2019; Sasikumar & Ramachandra, 2018).
When immune surveillance fails, cancerous tumors form. There are various schools of thought on the exact etiology of tumor escape mechanisms, but they largely encompass the following (Miliotou & Papadopoulou, 2018; Sasikumar & Ramachandra, 2018):
Altered immunogenicity: Antigen expression on the tumor cell surface is altered, allowing the antigen to go unrecognized by the humoral immune system, or the cell-mediated immune response can be blunted through cellular mutations.
Antigen modulation: Antibodies produced as part of the immune response cause antigens to enter the tumor cell or leave it.
Immune suppression: Cancer cells can produce substances that inhibit the body’s immune response.
Acquired deficiencies: Age- or disease-associated alterations can occur, including alterations in apoptosis mechanisms and signaling defects.
Immunologic aging: Alterations in T-cell functions can cause a decline in T-cell proliferation, thereby weakening the effect of the immune system.
Evasion: Tumors can dodge the immune system by appearing like normal cells, thereby not setting off inflammatory or warning signals that they are foreign.
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors work by blocking the receptors that cancer cells use to inactivate T-cells. T-cells may better differentiate between normal cells and cancer cells when this signal is blocked, augmenting the immune system’s response to the cancer cells. Checkpoint inhibitors are presently categorized as programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors. By blocking tumor cells from inactivating T-cells, these medications allow the T-cells to remain active and fight the tumor cells (Naidoo et al., 2015; Sasikumar & Ramachandra, 2018).
PD-1 Inhibitors/PD-L1 Inhibitors
PD-1 is a checkpoint protein on T-cells that normally acts as a type of “off switch” to keep them from attacking other cells in the body. PD-1 does this when it attaches to PD-L1, a protein on some normal and cancer cells. When PD-1 binds to PD-L1, it signals the T-cell to leave the neighboring cells alone. Some cancer cells have large amounts of PD-L1, which helps them evade immune attacks. PD-1 is a transmembrane protein expressed on the surface of circulating T-cells, B-cells, and NK-cells and is used to recognize “self” antigens from “non-self.” The binding of PD-L1, an inhibitory ligand expressed on various cancer cells, to PD-1 receptors on immune effector cells inhibits the immune effector cells from attacking the tumor cells. PD-1 and PD-L1 inhibitors prevent the formation of this complex and enable immune cells to attack tumor cells. Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells. Based on increasing treatment-response rates, PD-1 and PD-L1 inhibitors are being approved for various types of cancer, including melanoma, non–small-cell lung cancer, urothelial cancer, and, most notably, solid tumors with microsatellite instability-high (MSI-H) mutations and mismatch repair-deficient (dMMR) mutations. The approval of pembrolizumab (Keytruda) in 2015 for MSI-H or dMMR solid tumors was the first time a drug has been approved based on a biomarker test for a trait and not an anatomical tumor site, which represents a significant shift in cancer treatment. Examples of drugs that target PD-1 (PD-1 inhibitors) include pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo). Examples of drugs that target PD-L1 (PD-L1 Inhibitors) include atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi; Naidoo et al., 2015; Olsen et al., 2019; Sasikumar & Ramachandra, 2018).
These drugs help treat several types of cancer, including melanoma of the skin, non-small-cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. PD-L1 inhibitors/PD-1 inhibitors are generally well tolerated; however, patients can experience severe and possibly life-threatening autoimmune-related adverse effects. Although any organ system can be subjected to an autoimmune reaction, the most commonly observed reactions are colitis, hepatitis, endocrinopathies (thyroid and adrenals), pneumonitis, and skin rash progression to Stevens-Johnson syndrome. However, the most common side effects include fatigue, nausea, anorexia, coughing, diarrhea, skin rash, and itching (Naidoo et al., 2015; Olsen et al., 2019; Sasikumar & Ramachandra, 2018).
Chimeric Antigen Receptor (CAR) T-Cell Therapy
According to Miliotou and Papadopoulou (2018), CAR T-cell therapy is a novel but highly complex form of immunotherapy. T-cells are isolated from patients and genetically engineered to express a chimeric antigen receptor that recognizes a tumor-specific antigen. The compound is then injected into the patient, and the CAR T-cells induce cancer cell death. Miliotou and Papadopoulou (2018) report that the FDA has approved only a few types of CAR T-cell therapies to date. One is for treating aggressive, relapsed, or refractory B-cell acute lymphocytic leukemia and another is for aggressive, relapsed, or refractory non-Hodgkin lymphoma. These agents target a receptor called CD19, which is found on the cell surface in these cancers and many other hematological malignancies.
Miliotou & Papadopoulou (2018) emphasize that this therapy poses the risk of multiple potential toxicities that nurses must be prepared to recognize and respond to quickly. Two of the significant immune-related adverse effects of CAR T-cell therapy are cytokine release syndrome (CRS) and neurotoxicity. Cytokines are small protein molecules that are generally activated by a stimulus and induce a response by binding to specific receptors, affecting the growth and differentiation of WBCs. They also regulate immune and inflammatory responses by enhancing cytotoxic activity, secreting additional mediators, and amplifying the immune response when stimulated. CRS is characterized by symptoms of fever, nausea, vomiting, diarrhea, tachycardia, hypotension, tachypnea, and rash. These symptoms occur approximately 1-14 days after the treatment is administered and are a byproduct of cell lysis. As cancer cells die, they release cytokines into the body, stimulating these symptoms. Some patients may require hospitalization for supportive care, but most are managed on an outpatient basis. Complications of CRS may include renal dysfunction requiring dialysis, acute respiratory distress syndrome (ARDS), or a decline in cardiac ejection fraction (EF) or stroke volume (SV). A rare but severe effect that has been reported with these medications is disseminated intravascular coagulation (DIC), which is a potentially life-threatening condition in which blood clots form in small blood vessels throughout the body in combination with associated bleeding. These blood clots can block blood flow and induce harm to major organs such as the kidneys and liver. Neurotoxicity may present in patients as delirium, confusion, seizures, tremors, encephalopathy, incontinence, and paralysis. The onset of these symptoms is unique and considered biphasic, as symptoms generally occur concurrently with fevers or sedating medication during phase 1 (days 0-5) or phase 2 (after day 5). Symptoms are usually reversible and last about 2-4 days but can persist for a few weeks (Miliotou & Papadopoulou, 2018).
In addition to inhibition of the programmed cell death complex, other inhibitory modulators, such as CTLA-4, have been worthwhile targets in immunotherapy. Inhibitory effects of CTLA-4 occur in the priming phase of the immune response by interfering with signals required for T-cell activation. The binding of CTLA-4 to CD80/86 inhibits the activation of T-lymphocytes, resulting in a negative feedback signal that decreases immune response. The drug ipilimumab (Yervoy) induces T-cell activation by disabling the CTLA-4 feedback inhibition and allowing the immune system to activate. Ipilimumab (Yervoy) is currently FDA-approved for two distinct melanoma indications. It has demonstrated a synergistic effect with increased T-cell priming via CTLA-4 inhibition in the lymph nodes and cytotoxic activity via PD-1 inhibition in the tumor environment. Compared to drugs that target PD-1 or PD-L1, serious side effects are much more likely with these agents. Fatigue, skin rash, pruritis, and diarrhea are common. Clinically significant adverse effects are related to their ability to induce nonspecific inflammation throughout the body, leading to immune-mediated problems in the lungs (pneumonitis), intestines (enterocolitis), liver (hepatitis), kidneys (nephritis), hormone-making glands (endocrinopathies including thyroiditis and hypophysitis), eyes (uveitis), and several other organs. Most immune-related events are reversible with immunosuppressive steroid treatment but must be graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5 (2017) and managed per specific medication guidelines (Naidoo et al., 2015; Sasikumar & Ramachandra, 2018).
Other types of immunotherapies currently being explored include cancer vaccines and virus immunotherapy, in which viruses are used to infect cancer cells deliberately. This triggers an immune response against infected cancer cells. However, these modalities are still mainly in the clinical trial stage of development, with few agents approved by the US FDA. An example of a cancer vaccine is Provenge, which is designed to treat certain forms of prostate cancer; however, data regarding its effectiveness in improving life expectancy are limited and debatable (Sengupta, 2017).
In 2003, the completion of the Human Genome Project marked a dramatic shift in the understanding of cancer and other diseases (National Human Genome Research Institute [NHGRI], 2020). Project researchers mapped the entire human genetic code and discovered that every human cell comprises 20,000 to 30,000 genes. As a result, the past few decades have witnessed exploration into novel approaches to treating cancer and drug discovery (NHGRI, 2020).
Targeted agents are drugs formulated to attack specific parts of cancer cells to prevent tumor development or shrink existing tumors. Numerous proteins are located on the cellular membranes called growth factor receptors, which connect the external and internal cellular environments and are essential for cell growth and development. Alterations in genes lead to changes in these cellular proteins, stimulating the disruption of routine processes, inducing malfunction, and subsequently sanctioning cancer growth. The development of specialized drugs that block these growth factor receptors has been a tremendous part of cancer research throughout the last few decades. Targeted therapies impede the specific proteins that promote cancer growth through unique and distinctive pathways. Each type of targeted therapy works a little differently. However, all generally interfere with the ability of the cancer cells to grow, divide, repair, and communicate with other cells. Some targeted therapies focus on the external components and function of cancer cells. In contrast, others use small molecules that can enter the cell and disrupt the function of the cells, causing them to die. Others target receptors on the outside of the cell. In summary, targeted therapies can function by any of the following mechanisms:
block or turn off chemical signals that tell the cancer cell to grow and divide
alter proteins within the cancer cells, so the cells die
starve the tumor by cutting off blood supply and by preventing the formation of new blood vessels
help the immune system to destroy cancer cells
carry toxins or poison to the cancer cells directly to kill them without harming healthy, normal cells
starve the cancer of the hormones it needs to grow (Bar-Zeev et al., 2017; Sengupta, 2017)
These therapies are considered less toxic to normal cells and tissues than traditional chemotherapy agents. However, the downside to targeted therapies is that they contain the potential for cancer cells to become resistant, as they block specific pathways of cancer growth. Cancer cells can develop many growth pathways, so targeted therapies are most effective when combined with other cancer treatments, such as chemotherapy or radiation. However, while combination therapy has been deemed more effective, it does promote increased toxicity and the potential for side effects. Furthermore, despite significant advancements in targeted agents, they are generally not considered a replacement for traditional therapies. Targeted therapies are typically grouped into monoclonal antibodies and small molecule inhibitors (Olsen et al., 2019; Sengupta, 2017).
Therapies that target receptors are also known as monoclonal antibodies. Some monoclonal antibodies are combined with toxins, chemotherapy drugs, and radiation. Once these monoclonal antibodies attach to targets on the surface of cancer cells, the cells take up the cell-killing substances, causing them to die. Cells that do not have the target will not be harmed. Antibodies are part of the adaptive immune system. Normally, the body creates antibodies in response to an antigen (e.g., a protein in a germ) entering the body. The antibodies attach to the antigen to mark the antigen for destruction by the body's immune system. In a laboratory, scientists analyze specific antigens on the surface of cancer cells (target) to determine a protein to match the antigen. Then, using protein from animals and humans, scientists work to create a unique antibody that will attach to the target antigen like a key fits a lock. This technology allows treatment to target specific cells, causing less toxicity to healthy cells. Monoclonal antibody therapy can be done only for cancers in which antigens (and the respective antibodies) have been identified. Monoclonal antibodies work on cancer cells in the same way natural antibodies do, by identifying and binding to the target cells and then alerting other cells in the immune system to the presence of the cancer cells (Olsen et al., 2019; Sengupta, 2017).
Monoclonal antibodies may be used alone or combined with chemotherapy and are administered intravenously. How monoclonal agents are named provides clues about how they work. The ending letters (i.e., stem) of the name indicate what family the drug is from and how the drug works to kill cancer cells. Monoclonal antibodies always end with the stem “-mab.” The “-mab” family is used when receptor targets are overexpressed on the outside of cancer cells. Monoclonal antibodies have an additional layer of classification within their ‘sub stem,’ representing how the drug was comprised. Murine monoclonals, drugs ending in “-momab” (i.e., ibritumomab [Zevalin]), are composed of 100% mouse components and include conjugated antibodies, which are agents that are physically attached to antitumor agents such as radioisotopes, chemotherapy drugs, toxins, or other biologic agents. Chimeric monoclonals, drugs ending in “-ximab” (i.e., rituximab [Rituxan]), are primarily made of mouse protein with a (lesser) human protein component and therefore have a higher risk of a hypersensitivity reaction among patients due to the mouse component of the drug (Olsen et al., 2019).
Humanized mouse monoclonals, drugs ending in “-zumab” (i.e., bevacizumab [Avastin]) include a small percentage of mouse components or other protein, and the rest is human in origin. These medications generally induce less-severe allergic reactions. Finally, human monoclonal antibodies, ending in “-mumab” (i.e., panitumumab [Vectibix]) are fully human, and reactions to these medications are rare. Some monoclonal antibodies have additional information in their naming classification that designates the main target of the drug. For example, the “li” in ipilimumab identifies the immune system as the target, the “tu” in rituximab indicates the target is the tumor, and the “ci” in bevacizumab designates the circulatory system. Table 3 displays an overview of several monoclonal antibodies categorized according to class, target, and mechanism of action. The targets listed in Table 3, column 4 are receptors on the cell that the drug has been specially designed to block cellular signals, thereby disrupting or deactivating cancer growth. Two common targets of monoclonal antibodies include epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF; Olsen et al., 2019).
As stated earlier, hypersensitivity reactions are common in many kinds of monoclonal antibodies, with the most significant risk among the murine and chimeric groups due to the large mouse composition of these drugs. Conjugate monoclonal antibodies present the highest risk for bone marrow suppression and additional side effects since they are physically attached to a toxic or poisonous agent. Hypersensitivity symptoms can present in the same manner as chemotherapy hypersensitivity reactions and may be mild with facial flushing, pruritus, and hives. In other cases, they may progress to severe anaphylaxis requiring epinephrine. Other potential adverse effects of monoclonal antibodies include dyspnea and wheezing, fever and chills, headaches, rashes, nausea and vomiting, tachycardia, and bleeding. Since many patients endure rigors, shaking, chills, and fevers during the infusion, patients should be pre-medicated with acetaminophen (Tylenol) and an antihistamine. The nurses must remain vigilant and attentive to patients receiving infusions with monoclonal antibodies, as rigors require interruption of the infusion and possibly medication such as meperidine (Demerol) or corticosteroids. Many institutions have policies outlining the importance of slowly titrating the infusion rate of all monoclonal antibodies to reduce the risk of rigors, chills, and fevers. Slowing the infusion rate can also reduce the risk of prolonged rigors (Olsen et al., 2019).
Blood vessels carry oxygen and nutrients to the tissues that are necessary for growth and survival. In cancer, tumors need blood vessels to grow and spread. Angiogenesis is a process that occurs in both healthy and cancerous tissue to form new blood vessels by sending signals. Angiogenesis is primarily modulated through VEGF-receptors, which, as described earlier, are signal proteins produced to stimulate angiogenesis in normal and cancerous cells. Anti-angiogenesis stops the formation of new blood vessels by blocking the VEGF-receptors. Angiogenesis inhibitors, or VEGF-inhibitors, target the blood vessels that supply oxygen to the tumor cells, ultimately causing the cells to starve by cutting their nutrient supply. VEGF-inhibitors such as bevacizumab (Avastin) work by cutting the tumor’s blood supply via interfering with the VEGF-receptor. Without a blood supply, tumors stay small and eventually starve. Other angiogenesis inhibitors include interferon (Extavia) and thalidomide (Thalomid). The side effects of VEGF-inhibitors can be severe and include bleeding, headaches, hypertension, and proteinuria (protein spilling in the urine due to increased pressure in the kidneys). Patients require strict monitoring to ensure treatment is only administered if the blood pressure is below 140/90. Many patients require concurrent treatment with antihypertensives to maintain this range. A urinalysis must also be completed to assess for proteinuria before each dose, which is graded on a scale of 0-3+. Patients with protein of 2+ or greater on a simple urine dipstick test should undergo a further assessment with a 24-hour urine collection and treatment withheld for proteinuria ≥2 grams per 24 hours. Treatment may resume when proteinuria is <2 grams per 24 hours but should be discontinued permanently for patients who develop the rare side effect of nephrotic syndrome (Nettina, 2019; Olsen et al., 2019).
Given the risk of hemorrhage and delayed wound healing, it is contraindicated for patients to receive a VEGF inhibitor within 6 weeks of any surgical procedure. There is a risk of fistula development, an abnormal connection between 2 hollow spaces within the body, such as blood vessels, intestines, or other organs. VEGF inhibitors also carry a black box warning of bowel perforation, which is a hole in the lining of the intestines. Therefore, patients should be counseled on the importance of monitoring for any of the following symptoms, which can vary and may appear slowly or rapidly (Olsen et al., 2019):
abdominal pain, which is often severe and diffuse
severe abdominal cramping
fever/chills (Olsen et al., 2019)
Small Molecule Inhibitors
Small molecule drugs are pills or capsules taken orally that work on specific pathways. Like monoclonal antibodies, the generic naming of small molecule inhibitors is strategically devised to provide clues into how these medications work. Small molecule inhibitors end with the stem “-ib.” Since this family of drugs targets processes inside the cell, they must be small enough in molecular weight to enter the cell and interfere with proteins on both the inside and outside of the cell. Some examples include:
tyrosine kinase inhibition, sub stem “-tinib” (i.e., imatinib [Gleevac])
proteasome inhibition, “-zomib” (i.e., bortezomib [Velcade])
cyclin-dependent kinase inhibition (CDK 4/6), “-ciclib” (i.e., abemaciclib (Verzenio)
Several small molecule inhibitors have been approved by the US FDA and are on the market for cancer therapy. The most common molecular targets include tyrosine kinase inhibitors (TKIs), proteasome inhibitors, apoptosis targets, matrix metalloproteinases (MMPs), and heat shock proteins (HSPs). Another important class of small molecule inhibitors that warrant mention are the ADP-ribose polymerase (PARP) inhibitors. These drugs block PARP, a protein that has a critical role in cell growth, regulation, and repair. Because it helps cancer cells repair themselves and survive, their actions result in cancer cell death. PARP-inhibitors have revolutionized how BRCA mutation-positive cancers, such as ovarian cancer and breast cancers, are treated (Bar-Zeev et al., 2017; Olsen et al., 2019; Ring & Modesitt, 2018). Table 4 displays some small molecule inhibitors used for cancer treatment, although this is not a comprehensive list.
The side effect profile of these agents is distinctly different from cytotoxic chemotherapy. Oncology nurses should be aware of the toxicities and management of adverse effects. While some of them can induce bone marrow suppression (i.e., palbociclib [Ibrance] and abemaciclib [Verzenio]), these drugs are generally not associated with as much risk for infection and febrile neutropenia as cytotoxic chemotherapies are. The most common toxicities are dermatologic reactions, such as redness, swelling, pain, pins-and-needles on palms of hands and soles of feet, dermatitis and other skin rashes, pruritis, xerostomia (dry mouth), skin discoloration, hair thinning, and nail changes. They can induce toxic effects on the liver and kidneys, so routine laboratory monitoring and clinical assessment are essential (Bar-Zeev et al., 2017).
Some cancers require certain hormones to grow. Hormone therapies primarily follow two mechanisms of action: (a) prevent the body from producing the hormones that drive cancer growth and (b) prevent the hormones from reaching and acting on the cancer cells. The most common hormone-dependent cancers are breast and prostate, but other potentially hormone-driven cancers include endometrial (uterine), kidney, and ovarian cancers. Adverse effects of hormone treatment depend on the type of drug. They can differ between men and women but generally include hot flashes, night sweats, loss of libido, weight gain, vaginal dryness/atrophic vaginitis, joint aches or pains, mood changes, weight gain, and thinning or weakening of the bones (osteopenia or osteoporosis). Men may also experience impotence (inability to have or maintain an erection), a shrinking of the testicles, and gynecomastia (enlargement of breast tissue). Patients on hormonal therapy should be counseled on following a calcium-rich diet with at least 1,200 mg of dietary calcium daily. Patients who cannot get this recommended amount of calcium in their diet should consider calcium supplementation (DeVita et al., 2018; Olsen et al., 2019). Table 5 displays some hormonal therapies used for cancer treatment, although this is not a comprehensive list.
Oral Cancer Drugs
An oral cancer drug is any medication taken by mouth (in liquid, tablet, or capsule formulation) to treat cancer. Advancement in cancer treatment has led to the development of many new oral agents to treat cancer, which offers the convenience of taking the medication at home, with less time spent traveling to and from doctors’ offices and clinics. However, despite the popular misconception that oral cancer drugs are less toxic, they are equally as strong and effective as intravenous or injected drugs. There has been a surge in the development of novel oral treatments, many of which are not classified as cytotoxic chemotherapy based on their mechanism of action but still require the same precautions and patient education. Therefore, the term oral cancer medication has largely replaced oral chemotherapy and will be used throughout this section (Olsen et al., 2019).
Unique Features of Oral Agents
There are several special considerations with oral cancer treatments, as they pose unique safety challenges compared to traditional IV therapies. One of the most challenging issues with oral cancer treatment involves poor adherence, which substantially impacts the success of the treatment, side effects, toxicity, and patient safety. The NCCN (2022) established a task force to explore the impact of increased utilization of oral chemotherapy. They concluded that safety issues stem from a lack of checks and balances in administration, a risk of patient noncompliance, a lack of monitoring techniques, and a shift to patient management of oral chemotherapy. Oral cancer medications are prescribed at defined intervals based on the drug's mechanism of action, its half-life (the amount of time it takes for 50% of the drug to be excreted from the body), and its side effect profiles. Patients must be educated to take the medication as prescribed to ensure a constant level of the drug remains in the body to kill the cancer cells. Even a slight increase or decrease in the dose level can harm the drug’s efficacy or increase side effects. Patients must be counseled not to crush, chew, or split oral cancer pills, affecting how the medication works. Establishing a routine can help patients track their medication dosing schedule. Some strategies may include pillboxes that are filled each week, setting pill reminders on smartphones or tablets, enrolling in electronic medication reminders through a pharmacy, or using a simple paper pill diary, marking when the pill was taken to avoid overdosing (Olsen et al., 2019; Weingart et al., 2018).
Oral cancer drugs can be costly and may not be covered entirely by insurance and prescription plans. The financial burden is among the most common reasons for noncompliance with oral medications among cancer patients. Patients should be encouraged to speak to their HCP if they have difficulty affording their medication before stopping therapy. Some manufacturers offer co-pay assistance programs or have grants to fund free drug/compassionate use offerings. Several states have passed laws that require insurance companies to cover oral cancer medications in the same way they would cover intravenous cancer treatments (ACS, 2019).
Safe Medication Handling
Oral cancer drugs are potentially hazardous and require special precautions, especially for caregivers. As described by the 2016 ASCO and ONS chemotherapy administration safety standards, nurses should educate patients and caregivers on drug safety before oral cancer medications are prescribed (Olsen et al., 2019; Neuss et al., 2017). These recommendations are summarized according to the administration standards with the points listed below (Neuss et al., 2017).
General Safety Guidelines (Neuss et al., 2017)
- Keep cancer drugs in their original packaging until used or placed within the daily pillbox.
- Do not mix chemotherapy medications with other medications in the pillbox; they should always remain separate.
Perform hand hygiene (soap and water) before and after handling all medications, even if wearing gloves.
Take care not to let the medication contact household surfaces (such as countertops and tables). If they do, clean the surface thoroughly to prevent contact with traces of the drug.
Store oral cancer medications in a cool, dry place away from excess heat or sunlight.
Safe Medication Disposal (Neuss et al., 2017)
- Never discard chemotherapy medications in the trash, down the drain, or in the toilet.
Ask an HCP or pharmacist where to return unused medication, such as at a doctor’s office or pharmacy.
Empty pill bottles may be put in household trash but do not recycle. Before throwing it away, remove the label entirely.
Never reuse cancer medication pill bottles.
Exposure to Household Contacts (Neuss et al., 2017; Olsen et al., 2019)
Whenever possible, the patient should handle the medication themselves.
If anyone other than the patient comes in contact with oral cancer pills, they should be advised to wash with soap and water immediately. If any rash, irritation, or skin changes develop, they should contact the oncology office.
Caregivers should transfer the medication into a cup or spoon. If they need to pick up the medication with their hand, they are advised to wear disposable gloves to prevent unnecessary exposure (i.e., absorption via the skin).
Gloves should never be re-used but instead should be discarded in household trash after use, and trash should be double-bagged if there is contact with bodily fluids.
It takes approximately 48 hours for the body to excrete most cancer drugs. A small amount of the medication can exit in the patient’s urine, stool, vomit, or blood during this timeframe. There will be small amounts of the drug in these body fluids for patients who are continuously receiving oral cancer medication. Special precautions must be taken to protect caregivers and other household contacts:
Caregivers should wear disposable gloves when handling any body fluids from patients taking oral (or intravenous) cancer drugs.
Items soiled with body fluids should be kept in plastic bags until washed.
These items should be washed in hot water, separate from other laundry.
Pregnant caregivers should never come in contact with oral cancer medications or bodily fluids.
Low-pressure toilets should be double-flushed after each use by people on oral cancer medications.
The toilet lid should always be closed before flushing.
If any fluids splash from the toilet, the surface should be cleaned with disinfectant cleaner.
Take precautions to ensure pets do not drink from the toilet.
Chemoprevention is the use of natural or synthetic substances to reduce the risk of cancer or recurrence. Only a few agents have been shown to decrease cancer risk in high-risk individuals. These are hormonal therapies used in breast cancer, such as tamoxifen (Nolvadex) and raloxifene (Evista). Tamoxifen (Nolvadex) was the first chemopreventive agent approved by the US FDA for the risk reduction of breast cancer. Tamoxifen (Nolvadex) is a selective estrogen receptor modulator (SERM) that has been widely used to treat premenopausal women who have already been diagnosed with breast cancer to prevent a recurrence. More recent clinical trials have shown that tamoxifen (Nolvadex) may reduce the risk of breast cancer by nearly 50% in women who are at high-risk but have not yet been diagnosed. Therefore, tamoxifen (Nolvadex) can be used as primary chemoprevention to reduce the risk of cancer recurrence. Tamoxifen (Nolvadex) does carry a risk of the rare yet severe adverse effects of uterine sarcoma and venous thromboembolism/deep venous thrombosis (VTE/DVT). These risks must be considered, and patients must be counseled on these risks and must monitor for unilateral extremity swelling or postmenopausal bleeding. Raloxifene (Evista) was initially approved to treat osteoporosis but was found to have a similar impact as chemoprevention for breast cancer, without the risk of uterine sarcoma or VTE/DVT (Nettina, 2019; Olsen et al., 2019; Pfeiffer et al., 2018).
Third-generation aromatase inhibitors such as exemestane (Aromasin) and anastrozole (Arimidex) reduce the risk of estrogen receptor (ER)-positive breast cancer in postmenopausal women. Adverse effects include joint aches and bone thinning (osteopenia or osteoporosis). Imiquimod (Aldara) cream, a topical agent, has been approved to prevent nonmelanoma skin cancer. When applied to actinic keratosis, which are premalignant skin lesions, this agent helps limit the progression of the lesions to skin cancer. These medications are often prescribed to patients after genetic counseling and evaluation of hereditary risk patterns for cancer based on family history and other risk factors (Olsen et al., 2019). Other domains of chemoprevention include:
aspirin, which may decrease the risk of colorectal cancer
metformin, which may decrease the risk of breast, colon, endometrial, and possibly other cancers
statins, which may reduce the risk of prostate, lung, colorectal, and breast cancers (Nettina, 2019)
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