Pharmacology Chapter 14

use an effective contraceptive.

A 25-year-old female client is prescribed methotrexate to treat rheumatoid arthritis (RA). The nurse should teach the client to:

Higher tumor response rates

A 26-year-old man with testicular cancer is prescribed combination chemotherapy that involves using two drugs that are effective against testicular tumors. Combination drug therapy is superior to single-drug therapy because of:

Take special care when shaving or brushing her teeth.

A 42-year-old female with breast cancer has had a radical mastectomy. She will have radiation therapy and then begin chemotherapy. Drug therapy will consist of a combination of doxorubicin, cyclophosphamide, and paclitaxel. What will the nurse include in the teaching plan concerning the drug therapy?

dyspnea

A 63-year-old male patient has just begun treatment with IV paclitaxel. About 10 minutes into the infusion, the nurse becomes concerned about a possible anaphylactic reaction to the drug because the patient is experiencing:

Cardiotoxicity

A child is prescribed an anthracycline drug. The nurse would teach the parents to observe for signs and symptoms of what adverse effect?

proliferation

A client asks the nurse what cancer cell growth is called. What would the nurse tell the client?

Risk for infection

A client develops leukopenia after receiving chemotherapy. Which nursing diagnosis would be most appropriate?

Cell cycle

A client has been diagnosed with a brain tumor and is dealing with this diagnosis by seeking detailed information about cancer. The nurse would explain to the client that cancer is essentially a result of the disruption of what?

The medication combines with the metabolite of ifosfamide.

A client is administered mesna to prevent cystitis induced by ifosfamide. How will this medication combination prevent cystitis?

Ensure that all staff and visitors adhere to infection control precautions.

A client with leukemia is being treated with a combination of antineoplastics, including methotrexate. The client's most recent laboratory results indicate the client is experiencing bone marrow suppression. What is the nurse's priority action?

Hodgkin lymphoma

A client's chemotherapeutic regimen includes procarbazine. What is the client's most likely diagnosis?

Imbalanced nutrition: less than body requirements

A client's chemotherapy regimen has been deemed successful, but the client is experiencing debilitating nausea and vomiting. These adverse effects should signal the nurse to the possibility of what nursing diagnosis?

It is a common adverse effect of her treatment.

A female client is ending an extensive chemotherapeutic regimen that included cytotoxic antineoplastic drugs. What does the nurse understand about bone marrow toxicity in this client?

drink a lot of water.

A female patient is taking oral cyclophosphamide therapy for breast cancer. Because of possible adverse effects of the drug, the nurse will instruct the patient to:

Monitor the client closely and repeat LFTs routinely.

A male client is informed that the latest tests indicate that his cancer has spread to his liver. The client receives capecitabine as part of his treatment regimen. What would the nurse expect the health care provider to do?

exposure to carcinogens

A nurse educator is discussing the role of protooncogenes in the pathophysiology of cancer. What typically triggers protooncogenes to differentiate into oncogenes?

Inspect the site frequently for redness or swelling

A nurse is administering an antineoplastic extravasation occurs. How can the nurse best prevent tissue damage caused by extravasation?

"Brain tumors infiltrate the surrounding tissue."

A nurse on the oncology unit is caring for a client with an astrocytoma. The client has just been told that the tumor is growing very fast. The client asks the nurse how these tumors grow. What would be the nurse's best response?

Risk for Infection related to bone marrow suppression

A patient has just received the first dose of imatinib and the nurse on the oncology unit is amending the patient's care plan accordingly. What nursing diagnosis is most appropriate in light of this addition to the patient's drug regimen?

"Your hair will grow back, but the new hair may be a different color or texture."

A patient having chemotherapy is losing her hair. She asks the nurse if her hair will come back as it originally was. What is the best response by the nurse?

Intravenous

A patient is receiving carboplatin. The nurse would expect to administer this drug by which route?

Drug List

ALKYLATING AGENTS altretamine bendamustine busulfan carboplatin carmustine chlorambucil cisplatin cyclophosphamide ifosfamide lomustine mechlorethamine melphalan oxaliplatin procarbazine streptozocin temozolomide thiotepa trabectedin ANTIMETABOLITES capecitabine cladribine clofarabine cytarabine dacarbazine floxuridine fludarabine fluorouracil gemcitabine mercaptopurine methotrexate pemetrexed pentostatin pralatrexate thioguanine ANTINEOPLASTIC ANTIBIOTICS bleomycin dactinomycin daunorubicin doxorubicin epirubicin idarubicin mitomycin mitoxantrone valrubicin MITOTIC INHIBITORS cabazitaxel docetaxel eribulin etoposide ixabepilone paclitaxel vinblastine vincristine vinorelbine HORMONES AND HORMONE MODULATORS abiraterone anastrozole bicalutamide degarelix enzalutamide estramustine exemestane flutamide fulvestrant goserelin histrelin letrozole leuprolide megestrol mitotane nilutamide tamoxifen toremifene triptorelin pamoate CANCER CELL-SPECIFIC AGENTS abemaciclib afatinib alectinib axitinib belinostat bortezomib bosutinib cabozantinib carfilzomib ceritinib copanlisib crizotinib dabrafenib dasatinib enasidenib erlotinib everolimus ibrutinib idelalisib imatinib ixazomib lapatinib lenvatinib midostaurin neratinib nilotinib niraparib olaparib osimertinib palbociclib panobinostat pazopanib ponatinib regorafenib ribociclib romidepsin rucaparib ruxolitinib sonidegib sorafenib sunitinib temsirolimus trametinib vemurafenib venetoclax vismodegib vorinostat ziv-aflibercept MISCELLANEOUS ANTINEOPLASTICS arsenic trioxide asparaginase Erwinia chrysanthemi azacitidine bexarotene decitabine hydroxyurea irinotecan omacetaxine pegaspargase porfimer sipuleucel-T talc powder topotecan ANTINEOPLASTIC ADJUNCTIVE THERAPY allopurinol amifostine dexrazoxane leucovorin levoleucovorin mesna rasburicase

Adverse Effects

Adverse effects frequently encountered with the use of mitotic inhibitors include bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying cells of the bone marrow. GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration. Eribulin is associated with prolonged QT intervals. As with the other antineoplastic agents, effects of the mitotic inhibitors may include possible hepatic or renal toxicity, depending on the exact mechanism of action. Alopecia may also occur. These drugs also cause necrosis and cellulitis if extravasation occurs, so it is necessary to regularly monitor injection sites and take appropriate action as needed

Adverse Effects

Adverse effects frequently encountered with the use of the antimetabolites are listed here. To counteract the effects of treatment with one antimetabolite—methotrexate—the drug leucovorin or its isomer levoleucovorin is sometimes given

Adverse Effects

Adverse effects frequently encountered with the use of these alkylating agents are listed below; see Table 14.1 for a list of adverse effects specific to each agent. Amifostine (Ethyol) and mesna (Mesnex) are cytoprotective (cell-protecting) drugs that may be given to limit certain effects of cisplatin and ifosfamide, respectively

Adverse Effects

Adverse effects frequently encountered with the use of these antibiotics include bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying cells of the bone marrow. Toxic GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration, all of which are related to drug effects on the rapidly multiplying cells of the GI tract. As with the alkylating agents and antimetabolites, effects of antineoplastic antibiotics may include renal or hepatic toxicity, depending on the exact mechanism of action. Alopecia may also occur. Specific antineoplastic antibiotics are toxic to the heart and lungs. Box 14.10 discusses a cardioprotective drug that interferes with the effects of doxorubicin.

Key Points

Alkylating agents affect cellular RNA, DNA, or other cellular proteins, are cell cycle nonspecific, and are most effective against slow-growing tumors. Patients receiving alkylating agents may experience alopecia, nausea, and vomiting and need to be monitored for bone marrow suppression and CNS toxicity.

Contraindications and Cautions

Alkylating agents are contraindicated during pregnancy and lactation due to their potential for severe effects on the fetus and neonate. Caution is necessary when giving alkylating agents to any individual with a known allergy to any of them; with bone marrow suppression, which is often the index for redosing and dosing levels; or with suppressed renal or hepatic function, which may interfere with metabolism or excretion of these drugs and often indicates a need to change the dose.

Therapeutic Actions and Indications

Alkylating agents produce their cytotoxic effects by reacting chemically with portions of the RNA, DNA, or other cellular proteins, being most potent when they bind with cellular DNA. The oldest drugs in this class are the nitrogen mustards, and modifications of the structure of these drugs have led to the development of the nitrosoureas. These drugs are most useful in the treatment of slow-growing cancers such as various lymphomas, leukemias, myelomas; some ovarian, testicular, and breast cancers; and some pancreatic cancers. See Table 14.1 for usual indications for each of the alkylating agents. These agents are not used interchangeably.

Clinically Important Drug-Drug Interactions

Alkylating agents that are known to cause hepatic or renal toxicity should be used cautiously with any other drugs that have similar effects. In addition, drugs that are toxic to the liver may adversely affect drugs that are metabolized in the liver or that act in the liver (e.g., oral anticoagulants). Always check for specific drug-drug interactions for each agent in a nursing drug guide.

Contraindications and Cautions

All of these agents are contraindicated for use during pregnancy and lactation because of the potential risk to the fetus and neonate. Use caution when giving antineoplastic antibiotics to an individual with a known allergy to the antibiotic or related antibiotics, to prevent hypersensitivity reactions. Care is necessary when administering these agents to patients with the following conditions: bone marrow suppression, which is often the index for redosing and dosing levels; suppressed renal or hepatic function, which might interfere with the metabolism or excretion of these drugs and often indicates a need to change the dose; known GI ulcerations or ulcerative diseases, which may be exacerbated by the effects of these drugs; pulmonary problems with bleomycin or mitomycin, or cardiac problems with idarubicin or mitoxantrone, which are specifically toxic to these organ systems.

Drugs to Manage Rising Uric Acid Levels Associated with Tumor Lysis

Allopurinol (Aloprim, Zyloprim) inhibits the enzyme that allows the conversion of purines to uric acid, which is toxic to the body. It is used to help manage patients with leukemia, lymphoma, or other malignancies that result in elevated levels of serum and urinary uric acid levels. It lowers the level of uric acid to protect the kidneys and tissues. It is given orally at doses of 600 to 800 mg a day for 2 to 3 days with high fluid intake, and maintenance doses are then determined based on the patient's response and serum uric acid levels. Rasburicase (Elitek) is approved for the management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving antineoplastic therapy associated with tumor lysis and subsequent elevated serum uric acid levels. It is administered as a single daily IV infusion of 0.15 to 0.2 mg/kg over 30 minutes for 5 days. Chemotherapy should be started 4 to 24 hours after the first dose of rasburicase. Uric acid levels should be monitored frequently, using prechilled, heparinized vials that are kept in an ice-water bath. This analysis should be done within 4 hours of each rasburicase dose

Drugs that Are Used as Adjuncts in Antineoplastic Chemotherapy

Amifostine (Ethyol) is a cytoprotective (cell-protecting) drug that preserves healthy cells from the toxic effects of cisplatin. It is thought to react to the specific acidity and vascularity of nontumor cells to protect them, and it may also act as a scavenger of free radicals released by cells that have been exposed to cisplatin. Amifostine is given at a dose of 910 mg/m2 four times a day as a 15-minute IV infusion starting within 30 minutes after starting cisplatin therapy; timing is very important to its effectiveness. Now approved for use to prevent the renal toxicity associated with the use of cisplatin in patients with advanced ovarian cancer, amifostine is under investigation as an agent for protecting lung fibroblasts from the effects of paclitaxel. Because amifostine is associated with severe nausea and vomiting, concurrent administration of an antiemetic is recommended. It also can cause hypotension, and patients should be monitored closely for this condition. Mesna (Mesnex) is a cytoprotective agent that is used to reduce the incidence of hemorrhagic cystitis caused by ifosfamide or cyclophosphamide. Mesna, which is known to react chemically with urotoxic metabolites of ifosfamide, is given intravenously at the time of the ifosfamide injection at a dose that is 20% of the ifosfamide dose and is repeated 4 and 8 hours afterward. Because mesna has been associated with nausea and vomiting, an antiemetic may be useful. Dexrazoxane (Totect) is approved for the treatment of extravasation resulting from IV antineoplastic antibiotic chemotherapy. It is given as an IV infusion over 1 to 2 hours once daily for 3 days. Dosage is as follows: day 1, 1,000 mg/m2, maximum dose 2,000 mg; day 2, 1,000 mg/m2, maximum dose 2,000 mg; day 3, 3,500 mg/m2, maximum dose 1,000 mg. The mechanism of action that allows this drug to protect cells from damage related to extravasation is not understood, but it may block certain enzymes affected by the drugs. Dose should be reduced in patients with renal failure.

Wearing protective equipment

An oncology nurse is preparing to administer cytotoxic chemotherapy medications. Which measure best protects the nurse from harm related to the chemotherapy?

Antimetabolites

Antimetabolites (Table 14.2) are drugs that have chemical structures similar to those of various natural metabolites that are necessary for the growth and division of rapidly growing neoplastic cells and normal cells. Antimetabolites include capecitabine (Xeloda), cladribine (generic), clofarabine (Clolar), cytarabine (DepoCyt, Tarabine PFS), dacarbazine (generic), floxuridine (generic), fludarabine (generic), fluorouracil (Carac, Efudex, Fluoroplex), gemcitabine (Gemzar), mercaptopurine (Purixan), methotrexate (Rheumatrex, Trexall), pemetrexed (Alimta), pentostatin (Nipent), pralatrexate (Folotyn), and thioguanine (generic).

Contraindications and Cautions

Antimetabolites are contraindicated for use during pregnancy and lactation because of the potential for severe effects on the fetus and neonate. Caution is necessary when administering antimetabolites to any individual with a known allergy to any of them to prevent hypersensitivity reactions; with bone marrow suppression, which is often the index for redosing and dosing levels; with renal or hepatic dysfunction, which might interfere with the metabolism or excretion of these drugs and often indicates a need to change the dose; and with known GI ulcerations or ulcerative diseases that might be exacerbated by the effects of these drugs.

Key Points

Antimetabolites inhibit DNA production by inhibiting metabolites needed for the synthesis of DNA in susceptible cells. Antimetabolites are S-phase cell cycle specific and are used for some leukemias, as well as some GI and basal cell cancers. Bone marrow suppression, alopecia, and toxic GI effects are common adverse effects of antimetabolites.

Therapeutic Actions and Indications

Antimetabolites inhibit DNA production in cells that depend on certain natural metabolites to produce their DNA. They replace these needed metabolites and thereby prevent normal cellular function. Many of these agents inhibit thymidylate synthetase, DNA polymerase, or folic acid reductase, all of which are needed for DNA synthesis. They are considered to be S phase specific in the cell cycle. They are most effective in rapidly dividing cells, preventing cell replication, and leading to cell death (Fig. 14.5). The antimetabolites are indicated for the treatment of various leukemias and some GI and basal cell cancers (see Table 14.2 for usual indications for each agent). Use of these drugs has been somewhat limited because neoplastic cells rapidly develop resistance to these agents. For this reason, these drugs are usually administered as part of a combination therapy.

Clinically Important Drug-Drug Interactions

Antimetabolites that are known to cause hepatic or renal toxicity should be used with care with any other drugs known to have the same effect. Drugs that result in toxicity to the heart or lungs should be used with caution with any other drugs that produce that particular toxicity. Check for specific drug-drug interactions for each agent in a nursing drug guide.

Clinically Important Drug-Drug Interactions

Antimetabolites that are known to cause hepatic or renal toxicity should be used with care with any other drugs known to have the same effect. In addition, drugs that are toxic to the liver may adversely affect drugs that are metabolized in the liver or that act in the liver (e.g., oral anticoagulants). Check for specific drug-drug interactions for each agent in a nursing drug guide.

Antineoplastic Antibiotics

Antineoplastic antibiotics (Table 14.3), although selective for bacterial cells, are also toxic to human cells. Because these drugs tend to be more toxic to cells that are multiplying rapidly, they are more useful in the treatment of certain cancers. Antineoplastic antibiotics include bleomycin (generic), dactinomycin (Cosmegen), daunorubicin (Cerubidine), doxorubicin (Doxil), epirubicin (Ellence), idarubicin (Idamycin PFS), mitomycin (generic), mitoxantrone (generic), and valrubicin (Valstar) (Box 14.9).

Antiemetics and Cancer Chemotherapy

Antineoplastic drugs can directly stimulate the chemoreceptor trigger zone (CTZ) in the medulla to induce nausea and vomiting. These drugs also cause cell death, which releases many toxins into the system, which in turn stimulate the CTZ. Because patients expect nausea and vomiting with the administration of antineoplastic agents, the higher cortical centers of the brain can stimulate the CTZ to induce vomiting just at the thought of the chemotherapy. A variety of antiemetic agents have been used in the course of antineoplastic therapy. Sometimes a combination of drugs is most helpful. It should also be remembered that an accepting environment, plenty of comfort measures (e.g., environmental control, mouth care, ice chips), and support for the patient can help to decrease the discomfort associated with the emetic effects of these drugs. Antihistamines to decrease secretions and corticosteroids to relieve inflammation are useful as adjunctive therapies. Drugs that are known to help in treating antineoplastic chemotherapy-induced nausea and vomiting include the following: Dronabinol (Marinol) and nabilone (Cesamet) are synthetic derivatives of delta-9-tetrahydrocannabinol, the active ingredient in marijuana; this is not usually a first-line drug because of associated CNS effects. The usual dosage for dronabinol is 5 mg/m2 PO 1 to 3 hours before chemotherapy and repeated every 2 to 4 hours after chemotherapy. Nabilone is given orally as 1 to 2 mg PO twice daily initially, then daily during the cycle, and for 48 hours after the last dose of chemotherapy. Ondansetron (Zofran), granisetron (Kytril), and palonosetron (Aloxi), which is approved for use in children 1 month to 17 years, block serotonin receptors in the CTZ and are among the most effective antiemetics, especially if combined with a corticosteroid such as dexamethasone. The usual dosage is three 0.15-mg/kg doses IV or 8 mg PO three times a day starting 30 minutes before chemotherapy (ondansetron), or 10 mg/kg IV or 1 mg PO twice a day (granisetron), or 0.25 mg IV over 30 seconds, starting 30 minutes before chemotherapy (palonosetron). A combination oral product with netupitant (a human substance P/neurokinin receptor blocker) and palonosetron (Akynzeo) is available for added effects. Aprepitant (Emend) blocks human substance P/neurokinin 1 receptors in the CNS, blocking the nausea and vomiting caused by severely emetogenic antineoplastic drugs without effects on dopamine, serotonin, or norepinephrine. The usual dosage is 125 mg PO 1 hour before chemotherapy (day 1) and 80 mg PO once daily in the morning on days 2 and 3; given in combination with 12 mg dexamethasone PO on day 1 and 8 mg dexamethasone PO on days 2 to 4, and 32 mg ondansetron IV on day 1 only. Two benzodiazepines—alprazolam (Xanax), 0.5 mg PO four times a day, and lorazepam (Ativan), 2 to 6 mg/d PO—seem to be effective in directly blocking the CTZ to relieve nausea and vomiting caused by cancer chemotherapy; they are especially effective when combined with a corticosteroid. Haloperidol (Haldol), 0.5 to 2.0 mg PO four times a day or 2 to 25 mg IM or IV, is a dopaminergic blocker that also is believed to have direct CTZ effects. Metoclopramide (Reglan), 2 mg/kg IV over at least 30 minutes, calms the activity of the GI tract; it is especially effective if combined with a corticosteroid, an antihistamine, and a centrally acting blocker such as haloperidol or lorazepam. Prochlorperazine (generic), 5 to 10 mg PO three to four times a day or 5 to 10 mg IM, is a phenothiazine that has been found to have strong antiemetic action in the CNS; it can be given by a variety of routes.

Antineoplastic Drugs

Antineoplastic drugs can work by affecting cell survival or by boosting the immune system in its efforts to combat the abnormal cells (Fig. 14.3). Chapter 17 discusses the immune agents that are used to combat cancer. The present chapter focuses on those drugs that affect cell survival. The antineoplastic drugs that are commonly used today include alkylating agents, antimetabolites, antineoplastic antibiotics, mitotic inhibitors, hormones and hormone modulators, cancer cell-specific agents including protein tyrosine kinase inhibitors (which target enzymes specific to the cancer cells), and a group of antineoplastic agents that cannot be classified elsewhere. Other drugs are used to combat the serious adverse effects that can be associated with the antineoplastic drugs. These drugs are used as adjunctive therapy. Figure 14.4 shows sites of action of these drugs. Box 14.1 discusses use of these drugs across the lifespan.

Implementation with Rationale

Arrange for blood tests before, periodically during, and for at least 3 weeks after therapy to monitor bone marrow function to aid in determining the need for a change in dose or discontinuation of the drug (Box 14.5). Administer medication according to scheduled protocol and in combination with other drugs as indicated to improve effectiveness. Ensure that the patient is well hydrated to decrease risk of renal toxicity. Protect the patient from exposure to infection; limit invasive procedures when bone marrow suppression limits the patient's immune/inflammatory responses. Provide small, frequent meals; frequent mouth care; and dietary consultation as appropriate to maintain nutrition when GI effects are severe. Anticipate the need for antiemetics if necessary (Box 14.6). Arrange for proper head covering at extremes of temperature if alopecia occurs; a wig, scarf, or hat is important for maintaining body temperature. Provide patient teaching about the following:Follow the appropriate dosage regimen, including dates to return for further doses.Cover the head at extremes of temperature.Maintain nutrition if GI effects are severe.Avoid exposure to infection.Plan for appropriate rest periods because fatigue and weakness are common effects of the drugs.Consult with a healthcare provider, if appropriate, related to the possibility of impaired fertility.Use barrier contraceptives to reduce the risk of pregnancy during therapy.

Alkylating Agents

Because alkylating agents can affect cells even in the resting phase, these drugs are said to be non-cell cycle specific (see Fig. 14.4). They are most useful in the treatment of slow-growing cancers, which have many cells in the resting phase. Alkylating agents (Table 14.1) include the following drugs: altretamine (Hexalen), bendamustine (Bendeka, Treanda), busulfan (Busulfex, Myleran), carboplatin (generic), carmustine (BiCNU, Gliadel), chlorambucil (Leukeran), cisplatin (generic), cyclophosphamide (generic), ifosfamide (Ifex), lomustine (generic), mechlorethamine (Mustargen), melphalan (Alkeran), oxaliplatin (Eloxatin), procarbazine (Matulane), streptozocin (Zanosar), and temozolomide (Temodar), thiotepa (Tepadina), trabectedin (Yondelis).

Dealing with Bone Marrow Suppression

Bone marrow suppression is a frequently encountered adverse effect of antineoplastic chemotherapy. The cells in the bone marrow are rapidly turning over cells, constantly stimulated to produce blood components and so they are more likely to be affected by drugs that kill cells. The patient may experience a low red blood cell (RBC) count (anemia), low platelet counts, and low white blood cell (WBC) counts. The nurse is in the position to help the patient cope with these effects and prevent serious complications that occur. There are also drugs available that are often used to help stimulate the bone marrow.

Cancer

Cancer is a disease that can strike a person at any age. It remains second only to coronary disease as the leading cause of death in the United States. Treatment of cancer can be prolonged and often debilitating. The patient can experience numerous and wide-ranging complications and effects. All cancers start with a single cell that is genetically different from the other cells in the surrounding tissue. This cell divides, passing along its abnormalities to daughter cells, eventually producing a tumor or neoplasm that has characteristics quite different from those of the original tissue (Fig. 14.1). It is thought that all cells contain genes that would allow the cell to become cancer. These are called oncogenes and are responsible for the characteristics seen in cancer cells. In a healthy cell, they are not expressed. As the abnormal cells continue to divide, they lose more and more of their original cell characteristics. The cancerous cells exhibit anaplasia—a loss of cellular differentiation and organization, which leads to a loss of their ability to function normally. They also exhibit autonomy, growing without the usual homeostatic restrictions that regulate cell growth and control. This loss of control allows the cells to form a tumor.

Key Points

Cancers arise from a single abnormal cell that multiplies and grows. Cancer cells lose their normal function (anaplasia), develop characteristics that allow them to grow in an uninhibited way (autonomy), and have the ability to travel to other sites in the body that are conducive to their growth (metastasis). They also have the ability to grow new blood vessels to feed the tumor (angiogenesis). The goal of cancer chemotherapy is to decrease the size of the neoplasm so that the human immune system can deal with it.

Types of Cancer

Cancers can be divided into two groups: (1) solid tumors and (2) hematological malignancies such as the leukemias and lymphomas, which occur in the blood-forming organs. Solid tumors may originate in any body organ and may be further divided into carcinomas, or tumors that originate in epithelial cells, and sarcomas, or tumors that originate in the mesenchyme and are made up of embryonic connective tissue cells. Examples of carcinomas include granular cell tumors of the breast, bronchogenic tumors arising in cells that line the bronchial tubes, and squamous and basal tumors of the skin. Sarcomas include osteogenic tumors, which form in the primitive cells of the bone, and rhabdomyosarcomas, which occur in striated muscles. Hematological malignancies involve the blood-forming organs of the body, the bone marrow, and the lymphatic system. These malignancies alter the body's ability to produce and regulate the cells found in the blood.

Focus on Drug Therapy across the Lifespan Antineoplastic Agents

Children Antineoplastic protocols have been developed for the treatment of most pediatric cancers. Combination therapy is stressed to eliminate as many of the mutant cells as possible. Dose and timing of these combinations are crucial. Double-checking of dose, including recalculating desired dose and verifying the drug amount with another nurse, is good practice when giving these toxic drugs to children. Children need to be monitored closely for hydration and nutritional status. The nutritional needs of a child are greater than those of an adult, and this needs to be considered when formulating a care plan. These children need support and comfort and also need to be allowed to explore and learn like any other children. Body image problems, lack of energy, and the need to protect the child from exposure to infection can isolate a child receiving antineoplastic agents. The total care plan of the child needs to include social, emotional, and intellectual stimulation. Monitor bone marrow activity very carefully, and adjust the dose accordingly. Adults The adult receiving antineoplastic drugs is confronted with many dilemmas that the nurse needs to address. Changes in body image are common, with loss of hair, skin changes, GI complaints, and weight loss. Fear of the diagnosis and the treatment is also common with these patients. Networking support systems and providing teaching, reassurance, and comfort can have a tremendous impact on the success of the drug therapy. Pregnant and nursing women should not receive these drugs, which are toxic to the developing cells of the fetus. Pregnant women who are diagnosed with cancer are in a difficult situation: The drug therapy can have serious adverse effects on the fetus, and not using the drug therapy can be detrimental to the mother. Education, support, and referrals to appropriate specialists are important. Nursing women should find another method of feeding the baby to prevent the adverse effects to the fetus that occur when these drugs cross into breast milk. Use of barrier contraceptives is urged when these drugs are being used by women of childbearing age. Older Adults Older adults may be more susceptible to the CNS and GI effects of some of these drugs. Older patients should be monitored for hydration and nutritional status regularly. Safety precautions should be instituted if CNS effects occur, including increased lighting, assistance with ambulation, and use of supports. Many older patients have decreased renal and/or hepatic function. Many of these drugs depend on the liver and kidney for metabolism and excretion. Renal and liver function tests should be done before (baseline) and periodically during the use of these drugs, and dose should be adjusted accordingly. Protecting these patients from exposure to infection and injury is a very important aspect of their nursing care. Older patients are naturally somewhat immunosuppressed because of age, and giving drugs that further depress the immune system can lead to infections that are serious and difficult to treat. Monitor blood counts carefully, and arrange for rest or reduced dose as indicated.

A Cardioprotective Drug

Dexrazoxane (Zinecard), a powerful intracellular chelating agent, is a cardioprotective drug that interferes with the cardiotoxic effects of doxorubicin. The associated adverse effects are difficult to differentiate from those attributable to doxorubicin. This agent is approved for use to prevent the cardiomyopathy associated with doxorubicin in doses >300 mg/m2 in women with metastatic breast cancer. Dexrazoxane is given intravenously in a dose proportional to (10 times greater than) the doxorubicin dose 30 minutes before the doxorubicin is administered.

Pharmacokinetics

Generally, these drugs are given intravenously because they are not well absorbed from the GI tract. They are metabolized in the liver and excreted primarily in the feces, making them safer for use in patients with renal impairment than the antineoplastics that are cleared through the kidney.

Doxorubicin

IV/rapid/2 hrs/24-36 hrs

Vincristine

IV/varies/15-30 min

A Drug that Protects against an Antimetabolite

Leucovorin (generic) is an active form of folic acid that is used to "rescue" normal cells from the adverse effects of methotrexate therapy in the treatment of osteosarcoma. This drug is also used to treat folic acid deficiency conditions such as sprue, nutritional deficiency, pregnancy, and lactation. Leucovorin is given orally or intravenously at the time of methotrexate therapy and for the next 72 hours at a dose of 12 to 15 g/m2 PO or IV followed by 10 mg/m2 PO q6h for 72 hours. Use of this drug has been associated with pain at the injection site. In 2008, levoleucovorin (Fusilev), an isomer of leucovorin, was also approved to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdose of folic acid antagonists after high-dose methotrexate therapy in osteosarcoma. The drug is given IV for up to 4 days, and dose is determined by the serum methotrexate level of the patient. There are high calcium levels in the solution, and the drug needs to be given slowly.

Pharmacokinetics

Methotrexate is absorbed well from the GI tract and is excreted unchanged in the urine. Patients with renal impairment may require reduced dose and increased monitoring when taking methotrexate. Methotrexate readily crosses the blood-brain barrier. Cytarabine, clofarabine, floxuridine, fluorouracil, gemcitabine, pemetrexed, and pralatrexate are not absorbed well from the GI tract and need to be administered parenterally. They are metabolized in the liver and excreted in the urine, necessitating close monitoring of patients with hepatic or renal impairment who are receiving these drugs. Mercaptopurine and thioguanine are absorbed slowly from the GI tract and are metabolized in the liver and excreted in the urine.

Mitotic Inhibitors

Mitotic inhibitors (Table 14.4) are drugs that kill cells as the process of mitosis begins (see Fig. 14.5). These cell cycle-specific agents inhibit DNA synthesis. Like other antineoplastics, the main adverse effects of the mitotic inhibitors occur with cells that rapidly multiply: Those in the bone marrow, GI tract, and skin. Mitotic inhibitors include cabazitaxel (Jevtana), docetaxel (Taxotere), eribulin (Halaven), etoposide (generic), ixabepilone (Ixempra), paclitaxel (Abraxane), vinblastine (generic), vincristine (Marqibo), and vinorelbine (Navelbine).

Key Points

Mitotic inhibitors kill cells during the M phase and are used to treat a variety of cancers. These drugs are usually given intravenously. Extravasation could be a serious problem. Bone marrow suppression, alopecia, and toxic GI effects are common adverse effects of mitotic inhibitors.

Clinically Important Drug-Drug Interactions

Mitotic inhibitors that are known to be toxic to the liver or the CNS should be used with care with any other drugs known to have the same adverse effect. Check specific drug-drug interactions for each agent in a nursing drug guide.

Evaluation

Monitor patient response to the drug (alleviation of cancer being treated, palliation of signs and symptoms of cancer). Monitor for adverse effects (bone marrow suppression, GI toxicity, neurotoxicity, alopecia, renal or hepatic dysfunction). Evaluate the effectiveness of the teaching plan (patient can name the drug, dosage, possible adverse effects to watch for, and specific measures to help avoid adverse effects).

False

No cancer cells have been identified that can remain dormant for more than 2 years.

Nursing Diagnoses

Nursing diagnoses related to drug therapy might include the following: Acute pain related to GI, CNS, and skin effects of the drug Disturbed body image related to alopecia, skin effects, impaired fertility Imbalanced nutrition, less than body requirements Risk for infection Fear, anxiety related to diagnosis and treatment Deficient knowledge regarding drug therapy

Decreased Platelets

Platelet aggregation is the first step in preventing blood loss when a blood vessel is injured (see Chapter 48). When platelet levels are low, the patient is at increased risk of blood loss. Patients should be alert for increased bruising, bleeding while brushing their teeth, or increased bleeding with any injury. Protection is the best approach for these patients. Using a soft bristled toothbrush, using an electric razor, and avoiding sports or activities that could lead to injury are key teaching points.

Therapeutic Actions and Indications

Some antineoplastic antibiotics break up DNA links, and others prevent DNA synthesis. The antineoplastic antibiotics are cytotoxic and interfere with cellular DNA synthesis by inserting themselves between base pairs in the DNA chain. This, in turn, causes a mutant DNA molecule, leading to cell death (see Fig. 14.4). See Table 14.3 for usual indications for each antineoplastic antibiotic. Like other antineoplastics, the main adverse effects of these drugs are seen in cells that multiply rapidly, such as those in the bone marrow, GI tract, and skin. Their potentially serious adverse effects may limit their usefulness in patients with preexisting diseases and in those who are debilitated and, therefore, more susceptible to these effects.

Pharmacokinetics

The antineoplastic antibiotics are not absorbed well from the GI tract. They are given IV or injected into specific sites. They are metabolized in the liver and excreted in the urine at various rates. Many of them have very long half-lives (e.g., 45 hours for idarubicin, more than 5 days for mitoxantrone). Daunorubicin and doxorubicin do not cross the blood-brain barrier, but they are widely distributed in the body and are taken up by the heart, lungs, kidneys, and spleen. This can lead to toxic effects in these organs.

ALTERNATIVE THERAPIES AND CANCER

The diagnosis of cancer and the sometimes devastating effects of cancer treatment often drive patients to seek out alternative therapies, either as adjuncts to traditional cancer therapy or sometimes instead of traditional therapy. Because Asian Americans and Pacific Islanders often see drug therapy and other cancer therapies as part of a "yin/yang" belief system, they may turn to a variety of herbal therapies to "balance" their systems. The nurse should be aware of some potential interactions that may occur when alternative therapies are used: Echinacea—may be hepatotoxic; increases the risk of hepatotoxicity when taken with antineoplastics that are hepatotoxic Ginkgo—inhibits blood clotting, which can cause problems after surgery or with bleeding neoplasms Saw palmetto—may increase the effects of various estrogen hormones and hormone modulators; advise patients taking such drugs to avoid this herb St. John's wort—can greatly increase photosensitivity, which can cause problems with patients who have received radiation therapy or are taking drugs that cause other dermatological effects; has been shown to interfere with the effectiveness of some antineoplastic agents If a patient has an unexpected reaction to a drug, ask about whether he or she is using alternative therapies. Many of these agents are untested, and interactions and adverse effects are not well documented.

Therapeutic Actions and Indications

The mitotic inhibitors interfere with the ability of a cell to divide; they block or alter DNA synthesis, thus causing cell death. They work in the M phase of the cell cycle. These drugs are used for the treatment of a variety of tumors and leukemias. See Table 14.4 for usual indications for each of these agents

Decreased White Blood Cells

The neutrophils are the first WBCs stimulated with any injury or infection. They are phagocytes that are called to an injured area to remove damage and prevent further injury. A patient with low WBC counts is at high risk for infection and even cancer development. Protection is a key teaching point for these patients: Avoid crowded areas, don't visit sick friends or hospitals, avoid people who are known to be ill, avoid activities that could cause injury, and don't dig in the dirt without protective gloves (many pathogens live in the soil). Drugs called colony-stimulating agents may be used to stimulate WBC production when it falls dangerously low. Filgrastim (Neupogen), which comes in prefilled syringes for patients to use at home; pegfilgrastim (Neulasta); and tbo-filgrastim (Granix) (see Chapter 17) are administered by subcutaneous injection, with the patient's blood counts followed closely to determine dosing and duration of treatment.

Implement falls prevention measures Place the client on protective isolation Monitor the client's laboratory values closely Allow sufficient time for rest between scheduled activities

The nurse is preparing to administer a client's prescribed chemotherapy. The client has developed bone marrow suppression during treatment. What should the nurse include in the client's plan of care? Select all that apply.

slows the growth of cancer cells

The nurse is providing medication education to a client with breast cancer who has been prescribed tamoxifen. How should the nurse explain the action of the drug?

Planning

The patient will receive the best therapeutic effect from the drug therapy. The patient will have limited adverse effects to the drug therapy. The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety.

Decreased Red Blood Cells

The patient with a low RBC count will experience fatigue. The patient should be counseled to space activities during the day and incorporate rest periods into their daily schedule. Sometimes just knowing that this is a normal response is helpful to the patient. Epoetin alfa (Epogen, Procrit) or darbepoetin (Aranesp) (see Chapter 49) is often used to stimulate RBC production. These drugs act like endogenous erythropoietin to directly stimulate the cells in the bone marrow to make RBCs. Caution must be used to closely monitor the patient's hemoglobin level as levels over 10 g/dL have been associated with more rapid cancer growth and cardiac events. These drugs must be injected and the patient's lab values followed closely.

Contraindications and Cautions

These drugs should not be used during pregnancy or lactation because of the potential risk to the fetus or neonate. Use caution when giving these drugs to anyone with a known allergy to the drug or related drugs to decrease the risk of serious hypersensitivity reactions. Care is necessary for patients with the following conditions: Bone marrow suppression, which is often the index for redosing and dosing levels; renal or hepatic dysfunction, which could interfere with the metabolism or excretion of these drugs and often indicates a need to change the dose; known GI ulcerations or ulcerative diseases, which may be exacerbated by the effects of these drugs; and prolonged QT interval when using eribulin, which may prolong the QT interval leading to potentially serious arrhythmias.

Inhibits DNA production via replacing the natural substances needed for it

What best reflects the action of antimetabolites?

Causes of Cancer

What causes the cells to mutate and become genetically different is not clearly understood. In some cases, a genetic predisposition to such a mutation can be found. Some breast cancers, for example, seem to have a definite genetic link. In other cases, viral infection, constant irritation and cell turnover, and even stress have been blamed for the ensuing cancer. Stress reactions suppress the activities of the immune system (see Chapter 29), so if a cell is mutating while a person is under prolonged stress, research suggests that the cell has a better chance of growing into a neoplasm than when the person's immune system is fully active. Pipe smokers are at increased risk for development of tongue and mouth cancers because the heat of the pipe and chemicals in the pipe tobaccos and smoke continuously destroy normal cells, which must be replaced rapidly, increasing the chances for development of a mutant cell. People living in areas with carcinogenic or cancer-causing chemicals in the air, water, or even the ground are at increased risk of developing mutant cells in response to exposure to these toxic chemicals. Cancer clusters are often identified in such high-risk areas. Not everyone exposed to carcinogens or undergoing stress or having a genetic predisposition to develop cancer actually develops cancer. Researchers have not discovered what the actual trigger for cancer development is or what protective abilities some people have that other people lack. Most likely, a mosaic of factors coming together in one person leads to development of the neoplasm.

The drug will be effective through all phases of the cell cycle.

What should the oncology nurse understand when administering a cell cycle-nonspecific chemotherapeutic agent about its effect?

PREVENTING AND TREATING EXTRAVASATION

When an IV antineoplastic drug extravasates, or infiltrates into the surrounding tissue, serious tissue damage can occur. These drugs are toxic to cells, and the resulting tissue injury can result in severe pain, scarring, nerve and muscle damage, infection, and in very severe cases even amputation of the limb. Prevention is the best way to deal with extravasation. Interventions that can help to prevent extravasation include the following: Use a distal vein, and avoid small veins on the wrist or digits; never use an existing line unless it is clearly open and running well; start the infusion with plain 5% dextrose in water (D5W) and monitor for any sign of extravasation; check the site frequently, and ask the patient to report any discomfort in the area; and, if at all possible, do not use an infusion pump to administer one of these drugs because it will continue to deliver the drug under pressure and can cause severe extravasation. If extravasation occurs, there are specific antidotes to use with some antineoplastic drugs. The antidote is usually administered through the IV line to allow it to infiltrate the same tissue, but if the line has been pulled, a tuberculin syringe can be used to inject the antidote subcutaneously into the tissue surrounding the infiltrated area.

The process of creating new blood vessels to supply oxygen and nutrients to the cells

When describing the process of cancer cell growth to a client, the nurse addresses angiogenesis. Which description would the nurse include?

Imatinib

Which drug would have the least effect on healthy human cells?

Mitomycin

Which would the nurse identify as an antineoplastic antibiotic?

metastasis

ability to enter the circulatory or lymphatic system and travel to other areas of the body that are conducive to growth and survival; property of cancer cells

antineoplastic agents

designed to fight neoplasms, or cancers. Antineoplastic drugs alter human cells in a variety of ways. Their action is intended to target the abnormal cells that compose the neoplasm or cancer, having a greater impact on them than on normal cells. Unfortunately, normal cells also are affected by antineoplastic agents.

antineoplastic agent

drug used to combat cancer or the growth of neoplasms

alopecia

hair loss; a common adverse effect of many antineoplastic drugs, which are more effective against rapidly multiplying cells, such as those of hair follicles

Hematological effects

include bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying cells of the bone marrow. GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration, all of which are related to the drugs' effects on the rapidly multiplying cells of the GI tract. Hepatic toxicity and renal toxicity may occur, depending on the exact mechanism of action. Alopecia, or hair loss, related to effects on the hair follicles, may also occur. All drugs that cause cell death can cause a potentially toxic increase in uric acid levels. Allopurinol has been used to help alleviate this problem, and in 2004, a new drug, rasburicase (Elitek), was introduced to manage uric acid levels in patients receiving antineoplastics resulting in tumor lysis and elevated uric acid levels

Hematological effects

include bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia, secondary to the effects of the drugs on the rapidly multiplying cells of the bone marrow. Toxic GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration, all of which are related to drug effects on the rapidly multiplying cells of the GI tract. CNS effects include headache, drowsiness, aphasia, fatigue, malaise, and dizziness. Patients should be advised to take precautions if these conditions occur. There is a risk of pulmonary toxicity, including interstitial pneumonitis with these drugs. As with alkylating agents, effects of the antimetabolites may include possible hepatic or renal toxicity, depending on the exact mechanism of action. Alopecia may also occur

bone marrow suppression

inhibition of the blood-forming components of the bone marrow; a common adverse effect of many antineoplastic drugs, which are more effective against rapidly multiplying cells, such as those in bone marrow; seen as anemia, thrombocytopenia, and leukopenia

anaplasia

loss of organization and structure; property of cancer cells

autonomy

loss of the normal controls and reactions that inhibit growth and spreading; property of cancer cells

neoplasm

new or cancerous growth; occurs when abnormal cells have the opportunity to multiply and grow

Chlorambucil

oral/varies/1 hr/duration 15-20 hrs

Methotrexate

oral/varies/1-4 hrs IV/rapid/0.5-2 hrs

angiogenesis

the generation of new blood vessels; cancer cells release an enzyme that will cause angiogenesis or the growth of new blood vessels to feed the cancer cells

carcinoma

tumor that originates in epithelial cells

sarcoma

tumor that originates in the mesenchyme and is made up of embryonic connective tissue cells