Anticancer Drugs
Objectives
• Differentiate between cell cycle–specific and cell cycle–nonspecific anticancer drugs.
• Prioritize appropriate nursing interventions to use during the treatment of patients receiving anticancer drugs.
• Compare the uses and considerations for alkylating compounds, antimetabolites, antitumor antibiotics, hormones, and biotherapy agents.
• Contrast the guidelines for administering routine parenteral medications with IV chemotherapy preparation and administration.
• Discuss ways the nurse can avoid exposure to chemotherapeutic agents.
• Apply patient-centered collaborative care, including teaching, related to anticancer drugs.
• Develop a focused teaching plan about the uses and side effects of anticancer drugs.
Key Terms
adjuvant therapy, p. 505
alkylating agents, p. 507
antimetabolites, p. 513
antineoplastic drugs, p. 503
antitumor antibiotics, p. 518
apoptosis, p. 503
cell cycle–nonspecific drugs, p. 504
cell cycle–specific drugs, p. 504
combination chemotherapy, p. 503
cytoprotectant (chemoprotectant), p. 510
cytotoxic therapy, p. 503
doubling time, p. 504
growth fraction, p. 504
hormones, p. 524
leucovorin rescue, p. 513
metastasis, p. 505
myelosuppression, p. 505
nadir, p. 505
neoadjuvant chemotherapy, p. 505
palliative chemotherapy, p. 505
protocol, p. 505
taxanes, p. 521
vesicant, p. 510
vesication, p. 518
vinca alkaloids, p. 521
http://evolve.elsevier.com/KeeHayes/pharmacology/
The authors gratefully acknowledge the work of Carolee A. Polek, who updated this chapter for the eighth edition.
Cancer-related deaths rank second only to heart disease in the United States. Even though cancer-related mortality has decreased since the early 1990s, 1 in 3 women and 1 in 2 men are projected to develop cancer over their lifetime. Excluding skin cancers, the highest incidence rates in men are prostate, lung, and colorectal cancer. In women, breast, lung, and colorectal cancers occur with the highest frequency. Lung cancer remains the leading cause of cancer-related death regardless of gender.
The incidence and mortality rates of cancer differ by ethnicity. African-American men have higher incidence and death rates from cancer than do white men. African-American women have a lower incidence of cancer than white women, but a higher mortality rate. Latinos have a lower incidence than non-Latinos, except for cancer of the stomach, liver, and cervix. Cancer among Asian Americans has traditionally been lower than other ethnic groups, but incidence increases as immigrants adopt a more westernized lifestyle. The incidence of liver and stomach cancer is higher among Asian immigrants, secondary to higher rates of chronic hepatitis B in this group.
Cancer is a group of diseases in which abnormal cells grow out of control and may spread to other areas of the body. Deoxyribonucleic acid (DNA) is the genetic substance in the body cells that transfers information necessary for the production of enzymes and protein synthesis. In most cases, cancer is caused by damage to the DNA within the cell. Although some cancers are inherited, most develop when genes in a normal cell become damaged or lost (mutation). More than one mutation is required before a malignancy can develop. Therefore the development of cancer is a multistep process that may take years to complete.
Pharmaceuticals are often used to destroy cancer cells and are called by different names, including anticancer drugs, cancer chemotherapeutic agents, antineoplastic drugs, or cytotoxic therapy. In the 1970s, the use of two or more chemotherapy agents (combination chemotherapy) to treat cancer was adopted and led to improved response rates and increased survival times. Chemotherapy may be used as the sole treatment of cancer or in conjunction with other modalities (e.g., radiation, surgery, biologic response modifiers). Combination chemotherapy has proved to be effective in curing some cancers. When cancer cannot be cured, anticancer drugs may be given to control the disease for a period of months to years. If cancer can no longer be controlled, chemotherapy may be used to relieve disease-related symptoms or improve quality of life. This is called palliative treatment.
Genetic, Infective, Environmental, and Dietary Influences
Cancer is a genetic disease. Genes provide the instructions for the production and function of cellular proteins that are essential for normal cellular activities. Genetic defects may occur in a variety of ways, including deletion, translocation, duplication, inversion, or insertion of genetic material. When these defects cannot be effectively repaired, cells exhibit abnormal characteristics and unregulated growth. More than 2000 genes have been causally implicated in the formation of cancer. Cancers that have a proven genetic influence include breast, ovarian, prostate, endometrial, colon, pancreatic, and lung cancers; retinoblastoma; and malignant melanoma. Many more genetic influences are expected to be found. Environment, lifestyle, viruses, and diet can influence the development of these and other types of cancers. Box 37-1 gives examples of types of environmental products, viruses, and foods that have a carcinogenic effect on cancer development in humans.
Genes can cause cells to become cancerous in several ways. Proto-oncogenes are normal genes that are involved in the controlled growth, division, and death (apoptosis) of cells. An oncogene is a mutation in a proto-oncogene. An abnormal oncogene can effect cellular growth-control proteins and trigger unregulated cell division. Tumor-suppressor (TS) genes (anti-oncogenes) signal a cell to cease multiplying and act to stop the action of oncogenes. If TS genes become lost or dysfunctional, cells could reproduce uncontrollably. Other genes repair damage to DNA. If these DNA-repair genes are damaged, mutations are not mended and are subsequently passed on to the next generation of daughter cells. It may take a long time before sufficient cell mutations take place and cause cancer to develop. As a result, cancers more commonly occur in older individuals.
A number of viruses are associated with the development of cancer. The human papillomavirus (HPV) has been found in most women with invasive cervical cancer. Individuals with human immunodeficiency virus (HIV) may develop lymphomas and anal or genital cancers. The Epstein-Barr virus is found in almost all people with Burkitt's lymphoma in central Africa. This virus has been implicated in the development of nasopharyngeal cancer. Hepatocellular carcinoma (liver cancer) is linked to the hepatitis B or C virus. Other viruses that have a link to the development of cancer include human T-cell lymphotropic virus, type 1 (HTLV-1); human T-cell lymphotropic virus, type 2 (HTLV-2); and Kaposi sarcoma–associated herpes virus.
Bacteria can play a role in the development of cancer. The presence of Helicobacter pylori in the stomach is associated with an increased risk of developing gastric cancer. Some reports have indicated a link between certain bacteria and cancer of the gallbladder, colon, and lung. However, evidence that supports an association between bacterial infection and other cancers is unclear.
Environmental factors associated with the development of cancer include tobacco use, diet, infectious agents, chemicals, excessive sun exposure, and radiation. According to the American Cancer Society (ACS), the use of tobacco, an unhealthy diet, and inadequate physical activity account for 75% of cancer cases and deaths in the United States.
Cell Cycle–Nonspecific and Cell Cycle–Specific Anticancer Drugs
The cell cycle for normal and cancer cells, growth fraction, and doubling time are discussed in Unit XII (see Figure XII-1). See the discussion at the beginning of Unit XII for clarification of the cell cycle and definitions.
Anticancer drugs cause cell death by interfering with cell replication and are classified according to their action on the cell. Cell cycle–nonspecific (CCNS) drugs (phase-nonspecific drugs) act during any phase of the cell cycle, including the G0 phase. Cell cycle–specific (CCS) drugs (phase-specific drugs) exert their influence during a specific phase or phases of the cell cycle. CCS agents are most effective against rapidly growing cancer cells. In general, the CCNS drugs include the alkylating drugs (although some alkylating agents are CCS), antitumor antibiotics, and hormones. The CCS drugs include antimetabolites and vinca alkaloids. Figure 37-1 shows selected types of anticancer drugs and the phase of the cell cycle in which they are most effective.
Growth fraction and doubling time are two factors that play a major role in the response of cancer cells to anticancer drugs. Anticancer drugs are more effective against neoplastic cells that have a high growth fraction (i.e., a high percentage of actively dividing cells). Leukemias and some lymphomas have high growth fractions and thus respond well to anticancer drug therapy.
Solid tumors have a large percentage of their cell mass in the G0 phase, so they generally have a low growth fraction and are less sensitive to anticancer drugs. High-dose chemotherapy results in better tumoricidal (tumor-killing) effects. Depending on the type of cancer, malignant cell growth is usually faster in the earlier stages of tumor development. As the tumor grows, the blood supply decreases, thereby slowing the growth rate. Anticancer agents are more effective against small, fast growing tumors with sufficient blood supply. As the tumor enlarges, its growth fraction decreases and its doubling time increases, reducing the effectiveness of anticancer therapy. The vascularization in solid tumors can be inconsistent. Some areas of tumor may have an adequate blood supply, while other areas are poorly perfused. This characteristic may make some large tumors resistant to anticancer drugs and therefore difficult to treat.
Cancer Chemotherapy
Anticancer drugs are not selective, so both cancer cells and normal cells are affected. The side effects of chemotherapy are largely related to the toxic effects on normal cells. Antineoplastic agents are effective because normal cells are able to repair themselves and continue to grow, whereas cancer cells are less able to do so; thus, the side effects of chemotherapy are most often temporary. Chemotherapy is usually administered systemically for cancer that has spread to other parts of the body, for tumors in multiple sites, or for tumors that are too large to be removed through other means (e.g., surgery). The most common route of chemotherapy administration is via intravenous (IV) infusion, although other routes may be used, including oral, intramuscular, subcutaneous, intraperitoneal, intraventricular (intrathecal), intrapleural, intravesicular, intra-arterial, or topical.
Some types of cancer can be cured with chemotherapy (e.g., Hodgkin's disease, Burkitt's lymphoma, testicular cancer). Other types of cancer (e.g., breast cancer, colon cancer) may be treated with surgery first, followed by chemotherapy to eliminate any residual tumor cells (microscopic metastases) that may remain in the body. This is referred to as adjuvant therapy. Sometimes neoadjuvant chemotherapy may be given first to help shrink a large tumor, so that it can be surgically removed. Palliative chemotherapy is used to relieve symptoms associated with advanced disease (e.g., pain, shortness of breath) and improve quality of life.
Chemotherapy administration is guided by specific protocols that were developed based on the results of controlled research studies. The length of treatment is determined by the type and extent of the malignancy, type of chemotherapy given, expected side effects of these drugs, and the amount of time that normal cells need to recover. Chemotherapy is usually given in cycles to improve the likelihood that cancer cells will be destroyed and that normal cells can recover. The duration, frequency, and number of cycles of chemotherapy are based on the type and size of the tumor, whether the disease has spread to other areas of the body (metastasis), and the condition of the patient. Chemotherapy treatment may consist of one agent or a combination of agents. Combination chemotherapy may be administered on one day or spread out over several days. The duration of each treatment varies from minutes to days and may be repeated weekly, biweekly, or monthly, based on the protocol being followed. Selected anticancer/antineoplastic drugs are listed in Box 37-2 according to classification.
Combination Chemotherapy
Single-agent drug therapy is not usually used to treat cancer, because combinations of anticancer agents have demonstrated more effective tumoricidal activity. Chemotherapy is most effective when it is able to kill cells in all phases of the cell cycle. Using two or more chemotherapy drugs at a time (combination chemotherapy) makes this more likely to occur.
To maximize cell death, CCS and CCNS drugs are often combined. Each individual chemotherapy agent used in combination therapy should have proven tumoricidal activity. Using two or more drugs together may have a synergistic effect. In addition, each drug should have a different mode of action and different dose-limiting toxicities. The use of a combination of antineoplastic agents has the advantage of decreasing drug resistance and increasing destruction of cancer cells. Some of the combinations of anticancer drugs used in cancer treatment are presented in Table 37-1.
TABLE 37-1
SELECTED COMBINATIONS OF ANTICANCER DRUGS
| GENERIC (BRAND) | ACRONYM* | SELECTED USES |
| doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine (Velban), dacarbazine (DTIC) | ABVD | Hodgkin's lymphoma |
| fluorouracil (5-FU, Adrucil), doxorubicin/hydroxydoxorubicin (Adriamycin), cyclophosphamide (Cytoxan) | FAC* | Breast cancer, prostate cancer |
| cyclophosphamide (Cytoxan), doxorubicin/hydroxydoxorubicin (Adriamycin), methotrexate (Rheumatrex, Trexall) | CAM | Prostate cancer |
| cyclophosphamide (Cytoxan), epirubicin (Pharmorubicin), fluorouracil (5-FU, Adrucil) | CEF | Breast cancer |
| cyclophosphamide (Cytoxan), doxorubicin/hydroxydoxorubicin (Adriamycin), vincristine (Oncovin), prednisone, rituximab (Rituxan) | CHOP + rituximab (CHOP+R) | Non-Hodgkin's lymphoma |
| etoposide (VePesid, VP-16), leucovorin, fluorouracil (5-FU, Adrucil) | ELF | Esophageal cancer, stomach cancer |
| folinic acid (leucovorin), fluorouracil (5-FU, Adrucil), irinotecan (Camptosar) | FOLFIRI | Colorectal cancer |
| folinic acid (leucovorin), fluorouracil (5-FU, Adrucil), oxaliplatin (Eloxatin) | FOLFOX | Colorectal cancer |
| gemcitabine (Gemzar), capecitabine (Xeloda) | GEMCAP | Cancer of the pancreas |
| idarubicin (Idamycin), cytarabine (ARA-C, Cytosar), etoposide (VP-16, VePesid) | ICE | Acute myelogenous leukemia |
| mechlorethamine (Mustargen), vincristine (Oncovin), procarbazine (Matulane), prednisone | MOPP | Hodgkin's disease |
| melphalan (Alkeran), prednisone | MP | Multiple myeloma |
| mitomycin C (Mutamycin), vinblastine (Velban), cisplatin (Platinol) | MVP | Small cell lung cancer |
| paclitaxel (Taxol), carboplatin (Paraplatin) | PC | Non–small cell lung cancer |
| docetaxel (Taxotere), doxorubicin (Adriamycin), cyclophosphamide (Cytoxan) | TAC | Recurrent breast cancer |
| vinblastine (Velban), bleomycin (Blenoxane), cisplatin (Platinol) | VBP | Testicular cancer |
*Acronyms are based on the name of the chemotherapy agents used in a specific protocol (e.g., ABVD [Adriamycin, bleomycin, vinblastine, dacarbazine], FAC [fluorouracil, Adriamycin, cyclophosphamide]). Both generic and trade names are used in acronyms.
General Side Effects and Adverse Reactions
Anticancer drugs exert adverse effects on rapidly growing normal cells (e.g., skin, hair). These drugs can also affect cells in the gastrointestinal (GI) tract, mucous membranes, bone marrow, and reproductive system. When there is a significant decrease in the cells in the bone marrow (white blood cells, platelets, red blood cells) the condition is called myelosuppression. Following chemotherapy administration, the time at which the blood count is at the lowest is called the nadir and typically occurs 7 to 10 days after treatment. Table 37-2 lists the general adverse reactions to anticancer drugs on the fast-growing cells of the body. Selected nursing measures and considerations are included.
TABLE 37-2
GENERAL ADVERSE REACTIONS TO ANTICANCER DRUGS
| ADVERSE REACTIONS | NURSING MEASURES AND CONSIDERATIONS |
| Bone Marrow Suppression, Myelosuppression | |
| Low RBC count (anemia) | Assess for fatigue, shortness of breath, low blood pressure, increased heart rate, increased respiratory rate, and oliguria. Assess for cyanosis. Plan rest periods. Administer oxygen as prescribed. Elevate head of bed to facilitate breathing. Provide pain mediation if pain is increasing oxygen consumption. Provide assistance to bathroom. Monitor for mental status changes. Anemia may be treated with ferrous sulfate or infusions of RBCs. Erythropoietin may be administered to stimulate RBC production. |
| Low WBC count (neutropenia) | Susceptibility to infection increases as WBCs decrease. Visitors with colds or infections should take precautions (e.g., wear mask) or avoid visiting the patient. Report fever, chills, upper respiratory infections, or sore throat to health care provider. Health care providers and visitors should wash hands before and after contact with the patient. Neutrophils are the primary WBCs that fight infections. Usual signs of infection (pain, swelling, redness, warmth, pus) may be absent or greatly reduced in neutropenic patients. Monitor for increase (or decrease) in body temperature. Elevated temperature is considered a sign of infection. Avoid medications that may mask temperature. Immediately report temperatures of 101° F (38.3° C) or above to health care provider. Appropriate cultures (e.g., blood, urine, sputum) are collected, and an antibiotic regimen is initiated. Assess for localized infections. Auscultate breath sounds. Monitor WBC count. Colony-stimulating factors (e.g., filgrastim) may be administered to stimulate WBC production. |
| Low platelet count (thrombocytopenia) | Petechiae, bruising, bleeding of gums, and nosebleeds are signs of a low platelet count; report these signs to health care provider. Assess for bleeding, petechiae, and ecchymosis. Assess for occult bleeding in urine, feces, and emesis. Monitor platelet counts and bleeding time. Apply pressure to injection sites. Platelet transfusions may be needed. Avoid medications that may promote bleeding (e.g., aspirin). Avoid invasive procedures (e.g., injections, indwelling urinary catheters, rectal temperature). |
| GI Disturbances | |
| Anorexia | Loss of appetite may be related to anemia, pain, fatigue, or bitter taste caused by some chemotherapy agents. Provide small, frequent meals that are high in calories and protein. Plan rest periods. Address issues of pain control. Hard candy or ice chips may help relieve bitter taste. |
| Nausea and vomiting | Antineoplastic drugs often stimulate the chemoreceptor trigger zone (CTZ), leading to nausea and vomiting. Nausea and vomiting (N/V) may be caused by irritation of GI tract; effects of radiation to chest, abdomen, or brain; anxiety; constipation; pain; electrolyte imbalances; or other medications. Grading scales are useful to assess severity. Provide antiemetics before, during, and after chemotherapy. Assess for GI upset, and medicate appropriately. Minimize noise, stimulation, and odors. Frequent mouth care is recommended. |
| Diarrhea | Diarrhea may be one of three types: osmotic (absorption defects), secretory (bacterial infection, neoplasm), or exudative (secondary to chemotherapy). Chemotherapeutic agents most commonly associated with diarrhea are alkylating agents, antitumor antibiotics, and antimetabolites. Treatment (e.g., medications, diet changes) will depend on cause. |
| Diarrhea may be caused by other medications (e.g., antibiotics); comorbid conditions (e.g., Crohn's disease); or enteral feedings (e.g., tube feeding). Assess normal bowel habits; monitor for electrolyte imbalances and dehydration. Administer appropriate antidiarrheal medications (e.g., antibiotics, anticholinergics, antispasmodics, psyllium, kaolin and pectin, octreotide acetate). Teach patient to eat small, frequent meals; follow a low-residue diet; limit spicy, fatty foods; limit intake of salty foods, whole grains, fresh fruits and vegetables; limit caffeine and carbonated drinks; and avoid very hot or very cold foods (may stimulate peristalsis). Monitor intake and output. A grading scale may be useful to assess severity. | |
| Mucositis (stomatitis) | Many antineoplastic agents cause changes in oral mucosa; generally occur 2 to 14 days after initiation of therapy. Assess for taste changes, tissue swelling, redness, pain, dry mouth, white patches, or a white coating on the oral mucosa. Mucositis ranges from mild to severe. Symptomatic treatment may include frequent mouth rinses, topical anesthetics, antibiotics, antifungal medication, saliva substitutes, and pain medication. Patient should avoid commercial mouthwashes that contain alcohol. A soft toothbrush is recommended. Offer ice chips or ice pops to help relieve pain. Assess intake and output. Evaluate caloric needs. A grading scale may be useful to assess severity. |
| Other | Not all chemotherapeutic agents cause hair loss. Hair thinning, patchy baldness, or complete alopecia may occur, depending on drug. Hair on all areas of the body is affected. Hair loss may be gradual (progressing with each cycle of chemotherapy) or rapid. Hair regrowth usually occurs once chemotherapy is completed; texture may be somewhat changed. Before therapy, discuss potential hair loss and ways to address problem (wigs, scarves, hats, turbans). Assess for body image changes, concerns. |
| Alopecia | |
| Fatigue | Fatigue may be caused by chemotherapy, sleep disturbances, emotional distress, depression, bone marrow suppression, infection, pain, or electrolyte imbalances. |
| Assess fatigue using a visual analogue scale (0 = no fatigue; 10 = worst fatigue). Address conditions that might be contributing to fatigue (e.g., lack of sleep, pain, depression). Plan ways to help patient conserve energy. Plan a well-balanced diet. Encourage patient to participate in regular (but not strenuous) exercise. Encourage stress-reduction measures (e.g., relaxation, guided imagery). A grading scale may be useful in assessing fatigue. | |
| Infertility | If infertility occurs, it may be permanent. Pretreatment counseling is advised. |
GI, Gastrointestinal; RBC, red blood cell; WBC, white blood cell.
Anticancer Therapy in Outpatient Settings and in the Home
The administration of anticancer drugs in outpatient settings is cost-effective and convenient. Although chemotherapy regimens have become increasingly aggressive, most patients are not hospitalized unless they require close monitoring or are very ill. Some chemotherapy agents are administered in the home. Patients receiving highly potent drugs at home may need to be closely monitored for severe adverse reactions or to assure adequate hydration. When a chemotherapy drug is given in the home, a health care provider qualified to administer anticancer agents follows the policies provided by the oncologist and the home health care agency. To reduce the nurse's exposure to chemotherapy drugs (hazardous drugs, or HD) during intravenous (IV) administration, the following precautions should be followed to minimize occupational exposure:
• Use disposable powder-free gloves (nitrile, polyurethane, neoprene) that have been tested with HD when handling chemotherapy, regardless of route of administration.
• Wear gowns (disposable, impermeable, lint-free) during the administration of IV chemotherapy.
• When there is a risk of aerosol exposure, a National Institute for Occupational Safety and Health–approved respirator is necessary. Surgical masks do not provide adequate respiratory protection.
• Use a face shield or a combination of mask and face shield if there is a danger of splashing when administering chemotherapy or disposing of body fluids.
• Change gloves after chemotherapy administration and if they become contaminated or punctured.
• Cytotoxic drugs can be accidentally absorbed by inhalation, contact with skin or mucous membranes, and ingestion. The following guidelines should be followed:
1. Prepare chemotherapy in a separate work area. Use a plastic-backed absorbent pad to contain spills during preparation.
2. Wash hands before and after administration of chemotherapy.
3. Avoid hand-to-mouth or hand-to-eye contact while working with chemotherapy.
4. Refer to agency policy for priming IV tubing and disconnecting tubing after administration.
5. Wear gloves when disposing of body fluids (e.g., urine, feces, emesis) of patients who have received chemotherapy in the previous 48 hours.
6. Refer to agency policy for disposal of used equipment.
7. Refer to agency policy for chemotherapy spills or exposure.
Alkylating Drugs
One of the largest groups of anticancer drugs is the alkylating compounds. Alkylating agents cause cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing. Drugs in this group belong to the CCNS category and kill cells in various and multiple phases of the cell cycle. However, they are most effective against cells in the G0 phase. Alkylating agents are effective against many types of cancer, including acute and chronic leukemias, lymphomas, multiple myeloma, and solid tumors (e.g., breast, ovary, uterus, lung, bladder, and stomach). Drugs in this category are classified into several groups: mustard gas derivatives (e.g., cyclophosphamide [Cytoxan]), ethylenimines (e.g., thiotepa [Thioplex]), alkylsulfonates (e.g., busulfan [Myleran]), triazines (e.g., dacarbazine [DTIC]), nitrosoureas (e.g., carmustine [BiCNU]), and metal salts (e.g., cisplatin [Platinol]). Nitrosoureas are unique because they can cross the blood-brain barrier, making them useful in the treatment of brain cancer. Table 37-3 lists the alkylating drugs, uses, and considerations.
TABLE 37-3
ANTINEOPLASTICS: ALKYLATING DRUGS
| DRUG TYPE AND NAME | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Nitrogen Mustards | ||
| chlorambucil (Leukeran) | PO: 0.1-0.2 mg/kg/d (equals 4-8 mg/m2/d) for 3-6 wk | Lymphocytic leukemia, lymphomas, and cancer of the breast and ovaries. Side effects include nausea, vomiting, anorexia, diarrhea, abdominal upset, and leukopenia. Pregnancy category: D; PB: 99%;  : 1.5 h |
| cyclophosphamide (Cytoxan) | See Prototype Drug Chart 37-1. | |
| ifosfamide (Ifex) | IV: 1.2-2 g/m2/d for 5 d in combination with mesna | Testicular cancer, lymphoma, lung cancer, and sarcomas. Mesna, an uroprotective agent, is added to prevent hemorrhagic cystitis. Pregnancy category: D; PB: 69%-75%;  : 7-15 h (high dose) |
| mechlorethamine HCl (Mustargen) | IV: 0.4 mg/kg, or 12-16 mg/m2 Intracavitary: 0.2-0.4 mg/kg Topical: Dilute 10 g in 60 mL sterile water, apply with gloves (use precautions) |
Hodgkin's disease, solid tumors, and pleural effusion caused by cancer of the lung. Similar side effects as chlorambucil. Pregnancy category: D; PB: UK;  : 1 min |
| melphalan (Alkeran) | For multiple myeloma: 0.25 mg/kg/d; repeat every 6 wk For bone marrow transplant: IV 50-60 mg/m2 |
Multiple myeloma, melanoma, and cancers of the breast, ovary, and testes. Pregnancy category: D; PB: 30%;  : 1.5 h |
| temozolomide (Temodar) | PO: 150/mg/m2/d; repeat every 28 d | Refractory anaplastic astrocytoma. Pregnancy category: D; PB: 15%,  : UK |
| Nitrosoureas | ||
| carmustine (BiCNU, BCNU) | IV: 75-100 mg/m2/d for 2 d | Hodgkin's disease, multiple myeloma, melanoma, and brain tumors. May be used for cancer of the breast and lung. Nausea, vomiting, and stomatitis may occur. Pregnancy category: D; PB: UK;  : 15-30 min |
| lomustine (CeeNu, CCNU) | PO: 130 mg/m2 every 6 wk | Advanced Hodgkin's disease and brain tumors. Pregnancy category: D; PB: 50%;  : 1-2 d |
| streptozocin (Zanosar) | IV: 500 mg/m2/d for 5 d, repeat every 3-4 wk | Pancreatic islet cell tumor and cancer of the lung. May also be used for Hodgkin's disease and colorectal cancer. Nausea, vomiting, diarrhea, and leukopenia may occur. Pregnancy category: C; PB: UK;  : 30-45 min |
| Alkyl Sulfonates | ||
| busulfan (Myleran, Busulfex) | PO: 4-8 mg/d for 2-3 wk initially; then maintenance dose IV: 0.8 mg/kg |
Myelocytic leukemia. Monitor WBCs closely. May be used as preparation agent in bone marrow transplant. Pregnancy category: D; PB: UK;  : 2.5 h |
| Alkylating-Like Drugs | ||
| altretamine (Hexalen) | PO: 260 mg/m2/d in 4 equally divided doses for 14 d or 21 d | Ovarian cancer. Also used for breast, cervix, colon, endometrial, head/neck, and lung cancers; lymphomas. Nausea and vomiting and peripheral neuropathy may occur. Pregnancy category: D; PB: 6%;  : 13 h |
| carboplatin (Paraplatin) | IV: 360 mg/m2 every 4 wk Intraperitoneal: 200-650 mg/m2 in 2 L For bone marrow transplant 1600 mg/m2 IV in divided doses over 4 d |
Recurrent ovarian cancer. May be used as preparation agent in bone marrow transplant. Pregnancy category: D; PB: 0%;  : 2-6 h |
| cisplatin (Platinol) | IV: 50-100 mg/m2 every 3-4 wk For ovarian cancer: intraperitoneal: 100 mg/m2 every 3 wk |
Ovarian and testicular cancer. Used as adjunctive treatment. Has been used for cancer of the bladder, head and neck, and endometrium. Nausea, vomiting, peripheral neuropathy, stomatitis, tinnitus, and blurred vision may occur. Ototoxicity occurs in 30% of patients. Pregnancy category: D; PB: >90%;  : 58-75 h |
| oxaliplatin (Eloxatin) | IV: 85-130 mg/m2 infusion in 200-250 mL 5% dextrose in water | Metastatic colorectal cancer. Used with 5-FU and leucovorin. Ovarian cancer, head and neck cancer, and malignant melanoma. Pregnancy category: D; PB: >90%;  : 20-40 d |
| dacarbazine (DTIC) | IV: 375 mg/m2 every 2 wk | Metastatic malignant melanoma, sarcomas, neuroblastoma, and refractory Hodgkin's disease. May be given as an IV bolus (push) or by IV infusion. Common side effects are anorexia, nausea, and vomiting. Pregnancy category: C; PB: 5%-10%;  : 5 h |
| thiotepa (Thioplex) | IV: 0.3-0.4 mg/kg IV once every 1-4 wk Intracavitary: Bladder: 60 mg in 30-60 mL of sterile water weekly for 3-4 wk Effusions: 0.6-0.8 mg/kg every 1-4 wk |
Palliative therapy, especially for breast and ovarian cancer. Pregnancy category: D; PB: UK;  : 1.5-2 h |
Note: Chemotherapeutic doses and schedules will vary depending on protocol, body surface area (m2), age, functional status, and comorbid conditions. For a full discussion of body surface area in dosage calculation, see Chapter 14.
5-FU, Fluorouracil; d, day; FDA, U.S. Food and Drug Administration; GI, gastrointestinal; h, hour; IV, intravenous; min, minute; PB, protein-binding; 
, half-life; UK, unknown; WBC, white blood cell; wk, week; >, greater than; <, less than.
The side effects for alkylating drugs include nausea, vomiting, hemorrhagic cystitis, alopecia, anemia, leukopenia, thrombocytopenia, bone marrow suppression (anemia, leukopenia, thrombocytopenia), secondary malignancies, and sterility. Major dose-limiting toxicities may occur in the blood cell line (red blood cell, white blood cell, platelet) and urinary systems. General adverse reactions to chemotherapeutic drugs are listed in Table 37-2.
Cyclophosphamide
Mechlorethamine (nitrogen mustard, [Mustargen]), the first alkylating drug introduced for cancer treatment, became available for clinical use during World War II. Mechlorethamine is administered as part of a chemotherapy regimen to treat Hodgkin's disease, especially if the disease is resistant to other drug combinations. This drug is a severe vesicant that can cause tissue necrosis if it infiltrates into the tissues. Cyclophosphamide (Cytoxan), an analogue of nitrogen mustard, may be prescribed orally, intrapleurally, or IV. The patient should be well hydrated while taking this drug to prevent hemorrhagic cystitis (bleeding as a result of severe bladder inflammation). MESNA (2-mercaptoethane sulphonate sodium [MESNEX]) is a cytoprotectant (chemoprotectant) drug that is often given with high-dose cyclophosphamide to inactivate urotoxic metabolites in the bladder and minimize damage to this organ.
SafetyPharmacokinetics
Cyclophosphamide is well absorbed from the GI tract. Its half-life is moderate, and it is moderately protein-bound (<60%). The drug is metabolized by the liver, and less than 50% is excreted unchanged in the urine.
Pharmacodynamics
Cyclophosphamide, an early antineoplastic drug, is still prevalent in chemotherapy protocols to treat breast cancer, leukemia, lymphoma, multiple myeloma, ovarian cancer, retinoblastoma, and neuroblastoma. The onset of action begins in 2 to 3 hours; however, therapeutic effect may take several days. It is one of the anticancer drugs that can be administered orally.
Several drug interactions may occur with cyclophosphamide. Patients should report all medications they are taking, including over-the-counter (OTC) medicines and herbal supplements. Serious drug interactions can occur when taking cyclophosphamide and aspirin, the gout medication allopurinol (Lopurin, Zyloprim), phenobarbital (Luminal), warfarin (Coumadin), thiazide diuretics, and some psychiatric medications. Herbal Alert 37-1 lists herbal supplements that may also interact with cyclophosphamide.
Herbal Alert 37-1
Cyclophosphamide
• Use cautiously with garlic (antiplatelet activity), ginkgo (increased antiplatelet effect), echinacea (decreased effects of immunosuppressive drugs), ginseng (altered bleeding time), St. John's wort (may interfere with chemotherapy), and kava kava (increased risk for bleeding). Toxicity and actions of both cyclophosphamide and vitamin A are altered if given together. Do not use with mistletoe because it may promote cancer growth.
• Astragalus (Huang-qi; milk vetch root) stimulates the immune system and may help speed recovery from immunosuppressive chemotherapy. Astragalus has blood clot–fighting properties and may increase risk of bleeding when given with cyclophosphamide.
Side Effects and Adverse Reactions
The side effects of cyclophosphamide reflect those seen in this general class of antineoplastic drugs. Hemorrhagic cystitis is a serious problem that can arise when high doses of cyclophosphamide are given. Patients who receive a high dose should be assessed for cardiomyopathy and syndrome of inappropriate antidiuretic hormone secretion (SIADH) during treatment with this drug. In addition, cyclophosphamide may cause a change (darkening) in the skin or fingernails. Prototype Drug Chart 37-1 details the pharmacologic behavior of cyclophosphamide.
Nursing Process
Patient-Centered Collaborative Care
Alkylating Drugs: Cyclophosphamide
Assessment
Conduct a detailed medication history, including a list of all concurrent medications, including prescriptions, over-the counter medicines, antacids, dietary supplements, vitamins, and herbal supplements to avoid drug-drug interactions.
Obtain baseline information about patient's physical status. This should include height, weight, vital signs, laboratory values (complete blood count [CBC], uric acid, electrolytes, hepatic and renal studies, cardiopulmonary assessment, intake and output, skin assessment, daily activities status (i.e., ability to perform activities of daily living [ADLs], sleep-rest cycle), nutritional status, presence or absence of underlying symptoms of disease, and the use of current or past medication and treatment.
Assess laboratory value at the beginning of therapy and at specified time intervals (ranging from weekly to monthly) during therapy. Drug may be withheld if red blood cell, white blood cell, or platelet counts drop below predetermined levels.
Assess results of pulmonary function tests, chest radiographs, and renal and liver function studies during therapy.
Assess temperature; a 1- or 2-degree change in temperature may be a sign of infection.
Monitor for adequate intake and output.
Obtain baseline data regarding patient's psychosocial status, including educational level, ability and desire to learn, support systems, past coping strategies, presence or absence of emotional difficulties, and self-care abilities.
Assess patient and family knowledge related to therapeutic regimen.
Nursing Diagnoses
Risk for infection related to side effects of cancer chemotherapy treatments and disease condition
Risk for imbalanced nutrition, less than body requirements, related to GI side effects of chemotherapy
Impaired urinary elimination related to hemorrhagic cystitis caused by chemotherapy
Risk for bleeding related to effects of chemotherapy on the lining of the bladder and/or bone marrow suppression
Deficient knowledge related to chemotherapeutic protocol
Sexual dysfunction related to interference with normal menstrual cycle (in women) or lack of sperm production (in men)
Disturbed body image related to cancer treatment
Anxiety related to cancer diagnosis and unknown treatment outcomes
Risk for caregiver role strain related to cancer diagnosis, treatment, and care responsibilities
Planning
Patient's white blood cell, red blood cell, and platelet counts will be in the desired range.
Patient will remain free from infection.
Patient will maintain nutritional status (adequate fluid intake and output, sufficient caloric intake, stable weight).
Patient will maintain adequate urinary output.
Patient will remain free from symptoms of hemorrhagic cystitis.
Patient/family/caregiver will demonstrate understanding of chemotherapeutic protocol (e.g., dose, administration).
Potential body image disturbances will be discussed before therapy.
Patient/family/caregiver will verbalize an understanding of the importance of reporting chemotherapy-related side effects and adverse reactions.
Patient and family will verbalize strategies to minimize risks related to chemotherapy
Patient's side effects will be managed to a level that the patient can tolerate and are not life-threatening.
Nursing Interventions
Encourage patient to drink at least 2 L of fluid per day to promote excretion of cellular breakdown products and reduce the risk of hemorrhagic cystitis. Assess need for IV hydration.
Hydrate patient with IV and/or oral fluids before chemotherapy is administered.
Assess for signs and symptoms of hematuria, urinary frequency, or dysuria. Teach patient to empty bladder every 2 to 3 hours.
Monitor blood urea nitrogen (BUN) and creatinine prior to administration and throughout duration of treatment.
Handle drug with care during preparation and administration; avoid direct skin, eye, and mucus membrane contact with anticancer drugs. Follow protocols.
Monitor IV site frequently for irritation and phlebitis.
Administer prescribed premedications (30 to 60 minutes before giving drug).
Monitor fluid intake and output and nutritional intake.
Follow institution guidelines for safe handling, preparing, administering, and dispensing of chemotherapeutic agents.
Maintain strict medical asepsis during dressing changes and invasive procedures.
Patient Teaching
General
Teach patient to take cyclophosphamide early in the day to prevent accumulation of drug in the bladder during the night.
Remind patient to consult with health care provider before administration of any vaccines.
Advise patient to promptly report signs of infection (e.g., elevated temperature, fever, chills, sore throat, frequency and/or burning on urination, redness/swelling/pain near a wound); bleeding (e.g., bleeding gums, petechiae, bruises, hematuria, blood in the stool); and anemia (e.g., increased fatigue, dyspnea, orthostatic hypotension).
Advise patient not to visit anyone who has a respiratory infection. A decreased WBC count puts patient at high risk for acquiring an infection.
Emphasize protective precautions as necessary (e.g., hand washing, personal hygiene).
Explain to patient and family the rationale for chemotherapy.
Advise breastfeeding patient that cyclophosphamide is excreted in breast milk. Advise male patient that testicular atrophy and reversible oligospermia/azoospermia may occur.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Advise patients of childbearing age to use contraceptives during therapy and for 2 years after completion of therapy.
Provide information on where to purchase cosmetic supplies (e.g., wigs) should hair loss occur.
Side Effects
Advise patient about good oral hygiene with a soft toothbrush for stomatitis; have patient use a soft toothbrush when platelet count is <50,000/mm3.
Remind premenopausal women that they may experience amenorrhea, menstrual irregularities, or sterility; advise male patients that they may experience impotence.
Advise patient of possible hair loss; recommend a wig, hairpiece, scarf, or turban.
Assess for use of alternative/complementary therapy that may interact with chemotherapy agent.
Diet
Cultural Considerations
In some cultural groups, health care decisions are made by consensus, and the family plays a key role in filtering the information given to a patient. Issues related to informed consent and full disclosure of medical information may cause distress in cultural groups who place the needs of the family above the needs of the individual. Interactions should be modified based on family structure, religious values and beliefs, time orientation, cultural health practices, and verbal and nonverbal communication.
Cultural assessment tools can provide general guidelines for health care providers.
Hyperpigmentation of the tongue and oral mucosa after administration has been reported in African Americans. Incidence rate of high-grade neutropenia may be higher in Asian patients.
Evaluation
Prototype Drug Chart 37-1
Cyclophosphamide
| Drug Class | Dosage |
| Alkylating drug Trade Name: Cytoxan Pregnancy Category: D | A: PO: Initially: 1-5 mg/kg over 2-5 d IV: Initially: 40-50 mg/kg in divided doses over 2-5 d; max: 100 mg/d; C: PO/IV: Initially: 1-5 mg/kg in divided doses or 50-150 mg/m2 Many other dose regimens are used. Dose varies based on indicated use. Adjust dose if bone marrow suppression (myelosuppression) occurs. |
| Contraindications | Drug-Lab-Food Interactions |
| Hypersensitivity, severe myelosuppression Caution: Pregnancy, liver or kidney disease | Drug: Decreases digoxin level. Increases drug action of barbiturates, chloramphenicol half-life, and effects of anticoagulant drugs. Duration of leukopenia may be prolonged if given with thiazide diuretics. Potentiates doxorubicin (Adriamycin) cardiomyopathy. Actions and toxicities of allopurinol, probenicid, colchicine, phenothiazines, potassium iodide, imipramine, warfarin, and succinylcholine are altered if given with cyclophosphamide. Toxicity increased if given with corticosteroids, phenytoin, or sulfonamides. |
| Herb: Use cautiously with garlic, ginkgo, echinacea, ginseng, St. John's wort, kava kava, grapeseed. Toxicity and actions of both cyclophosphamide and vitamin A are altered if given together. Do not use with mistletoe. Do not give with Astragalus membranaceus (Beg Kei, Buck Qi, Huang Chi, Milk Vetch, Yellow Leader); may decrease effects of chemotherapy | |
| Lab: Suppresses positive reaction to uric acid, purified protein derivative, mumps, Candida; Papanicolaou test (Pap smear) may cause a false-positive result | |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: PO: Well absorbed Distribution: PB: <60% Metabolism:  : 3-12 h | PO/IV: Onset: 7 d Peak: 10-14 d Duration: 21 d |
| Excretion: 25%-40% in urine unchanged; 5%-20% in feces | |
| Nadir: 7-14 d | |
| Therapeutic Effects/Uses | |
| Breast, lung, ovarian cancers; leukemias; lymphomas, multiple myeloma. An immunosuppressant agent | |
| Mode of Action: Inhibition of protein synthesis through interference with DNA replication by alkylation of DNA | |
| Side Effects | Adverse Reactions |
| Nausea, vomiting, diarrhea, weight loss, hematuria, alopecia, impotence, sterility, ovarian fibrosis, headache, dizziness, dermatitis | Hemorrhagic cystitis, secondary neoplasm, myelosuppression Life-threatening: Leukopenia, thrombocytopenia, cardiotoxicity (very high doses), hepatotoxicity (long-term) |
A, Adult; C, child; d, day; DNA, deoxyribonucleic acid; h, hour; IV, intravenous; maint, maintenance; max, maximum; PB, protein-binding; PO, by mouth; 
, half-life.
Note: Chemotherapy drug doses are based on body weight and prescribed either as milligrams per kilogram (mg/kg) or milligrams per meter squared (mg/m2). Doses will also vary based on drug protocol, type and stage of cancer, age, functional status, and comorbid conditions (e.g., heart disease).
Antimetabolites
Antimetabolites resemble natural metabolites that synthesize, recycle, and break down organic compounds for use by the body. However, antimetabolites disrupt metabolic processes and can inhibit enzyme synthesis. They are classified as CCS and exert their effects in the S phase (DNA synthesis and metabolism) of the cell cycle. This group is classified according to the substances with which they interfere; they include folic acid (folate) antagonists (e.g., methotrexate [Rheumatrex, Trexall], pemetrexed [Altima]), pyrimidine antagonists (e.g., fluorouracil [Adrucil]), purine antagonists (e.g., 6-mercaptopurine [Purinethol]), adenosine deaminase inhibitors (e.g., fludarabine [Fludara]), and ribonucleotide reductase inhibitors (e.g., hydroxyurea (Hydrea), 2-deoxycoformycin (pentostatin [Nipent]).
Antimetabolites are used to treat acute and chronic leukemia, myelodysplastic syndrome (MDS), breast cancer, head and neck cancer, lung cancer, osteosarcoma, and lymphomas. Two drugs in this classification, fluorouracil, also known as 5-FU [Adrucil]), and floxuridine (FUDR) are considered CCNS as well as CCS.
Methotrexate, also designated as MTX (Rheumatrex, Trexall), a folic acid antagonist, is used for the treatment of both cancerous and noncancerous (e.g., rheumatoid arthritis, psoriasis) conditions. Methotrexate is also used to induce miscarriage in patients with ectopic pregnancies. Methotrexate acts as a substitute for folic acid, which is needed for the synthesis of proteins and DNA. Cancer patients receiving high doses of MTX must be given leucovorin calcium to “rescue” (leucovorin rescue) normal cells from the adverse effects of the drug.
Numerous drug interactions may occur with MTX. Protein-bound drugs (e.g., aspirin, phenytoin) increase the toxicity of MTX. Nonsteroidal antiinflammatory drugs (NSAIDs) increase and prolong MTX levels. Cotrimoxazole (Bactrim) and pyrimethamine (Daraprim) increase MTX levels. Patients who are taking penicillins, cyclooxygenase 2 (COX-2) inhibitors, and OTC herbs should share this information with their physician, because these products interact with MTX. Table 37-4 lists the antimetabolite drugs, uses, and considerations.
TABLE 37-4
ANTINEOPLASTICS: ANTIMETABOLITES
| DRUG TYPE AND NAME | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Folic Acid Antagonists | ||
| methotrexate (MTX) | IV: low dose: 10-50 mg/m2; medium dose: 100-500 mg/m2; high dose: 500 mg/m2 (and higher followed by leucovorin rescue) IT: 10-15 mg/m2 IM: 25 mg/m2 |
Solid tumors, sarcomas, choriocarcinoma, leukemia. At higher doses, patients should be well hydrated; keep urine pH at 7.0 for drug solubility for excretion. Higher doses require use of leucovorin as a rescue for normal cells. Pregnancy category: D; PB: 50%;  : 8-15 h |
| pemetrexed disodium (Alimta) | IV: 500 mg/m2 day 1 of every 21-d cycle | A multitargeted antifolate to treat mesothelioma and non– small-cell lung cancer. Pregnancy category: D; PB: 81%;  : 3.5 h |
| trimetrexate glucuronate (Neutrexin) | IV: 45 mg/m2/d; infuse over 60-90 min for 21 d | Alternative drug therapy for Pneumocystis carinii pneumonia; treatment for patients with AIDS. May be used for colorectal cancer. Monitor CBC. Pregnancy category: D; PB: 86%-94%;  : 11-13 h |
| Pyrimidine Analogues | ||
| azacitidine (Vidaza) | SubQ: 75 mg/m2 IV: 75-100 mg/m2/d for 7 d, repeated every 4 wk |
Treatment of chronic myelomonocytic leukemia. Pregnancy category: D; PB: UK;  : 41 min |
| capecitabine (Xeloda) | PO: 2500 mg/m2/d in two divided doses for 2 wk | Solid tumors, sarcomas, choriocarcinoma, leukemia. At higher doses, patients should be well hydrated; keep urine pH at 7.0 for drug solubility for excretion. Pregnancy category: D; PB: 50%;  : 8-16 h |
| cytarabine (Cytosar-U, ARA-C, cytosine arabinoside) | For leukemia IV: 100 mg/m2/d continuous infusion for 5-10 d For head and neck cancer: 1 mg/kg every 12 h for 5-7 d IV or subQ For bone marrow transplant 1.5 mg/m2 continuous infusion for 48 h IT: 5-75 mg/m2 every 2-7 d |
Acute leukemias and lymphomas. Also used as an immunosuppressive drug after organ transplant. May be used in combination with other anticancer drugs. Nausea, vomiting, leukopenia, and thrombocytopenia are common side effects. Pregnancy category: D; PB: 15%;  : 1-3 h |
| floxuridine (FUDR) | Intra-arterial (hepatic): 0.1-0.6 mg/kg/d for 7-14 d. Delivered by slow infusion pump | Metastatic colon cancer and hepatomas. Pregnancy category: D; PB: UK;  : 20 h |
| 5-fluorouracil (5-FU, Adrucil) | See Prototype Drug Chart 37-2. | |
| gemcitabine HCl (Gemzar) | For breast cancer: IV: 1250 mg/m2 over 30 min days 1 and 8 of 21-d cycle For pancreatic cancer: IV: 1000 mg/m2 over 30 min weekly for up to 7 wk For NSCL: IV: 1000 mg/m2 over 30 min days 1 and 8 and 15 For ovarian cancer: IV: 1000 mg/m2 over 30 min days 1 and 8 of 21-d cycle |
Advanced or metastatic adenocarcinoma of the pancreas, non–small-cell lung cancer and bladder cancer. Acts at S phase of cell cycle. Monitor leukocytes and platelet count; reduce dose if values are extremely low. Pregnancy category: D; PB: UK;  : 1-10 h |
| nelarabine (Arranon) | A: 1500 mg/m2 IV over 2 hours on days 1, 3, and 5; repeat every 3 wk C: 650 mg/m2 IV over 1 h on days 1, 2, 3, 4, 5; repeat every 3 wk |
Treatment of refractory or relapsed T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Pregnancy category: D; PB: <25%;  : 30 min-3 h |
| Purine Analogues | ||
| cladribine (Leustatin) | IV: 0.09 mg/kg/d as a continuous infusion for 7 d | For treatment of hairy cell leukemia and chronic lymphocytic leukemia. Adverse reactions: bone marrow suppression, fever, nausea, vomiting, diaphoresis. Pregnancy category: D; PB: 20%;  : 5.4 h |
| clofarabine (Clolar) | IV: 52 mg/m2 IV over 2 h daily for 5 d | To treat refractory or relapsed acute lymphoblastic leukemia in children. Pregnancy category: D; PB: 47%;  : 105 min |
| fludarabine (Fludara) | PO: 40 mg/m2/d for 5 d; repeat every 28 d IV: 25 mg/m2; infuse over 30 min daily for 5 d; repeat every 28 d |
Chronic lymphocytic leukemia in patients who have not responded to other alkylating drugs; low-grade non-Hodgkin's lymphoma. Anorexia, nausea, diarrhea, fever, and peripheral edema may occur. Pregnancy category: D; PB: UK;  : 9 h |
| 6-mercaptopurine (Purinethol) | PO: Induction dose 2.5 mg/kg/d followed by maintenance dose | First used in 1952 for treating acute lymphatic leukemia. Also used as immunosuppressive drug. Adverse reactions include hepatotoxicity, bone marrow suppression, hyperuricemia. Pregnancy category: D; PB: 19%;  : 45 min |
| thioguanine (6-thioguanine, Lanvis) | PO: A: 100 mg/m2 every 12 h for 5-10 d C: 100 mg/m2 every 12 h for 5-10 d OR 1-3 mg/kg/d |
Acute and chronic myelogenous leukemia. Long duration of action. Pregnancy category: D; PB: UK;  : 2-11 h |
| Ribonucleotide Reductase Inhibitors (Enzyme Inhibitors) | ||
| hydroxyurea (Hydrea) | PO: 20-30 mg/kg/d | Melanoma, resistant chronic myelocytic leukemia, and ovarian cancer. Long duration of action. Pregnancy category: D; PB: UK;  : 3-4 h |
| pentostatin (Nipent) | IV: 4 mg/m2 every other wk | Hairy cell leukemia refractory to alpha-interferon. Very long duration of action. Pregnancy category: D; PB: UK;  : 6 h |
Note: Chemotherapeutic doses and schedules will vary depending on protocol, body surface area (m2), age, functional status, and comorbid conditions. For a full discussion of body surface area in dosage calculation, see Chapter 14.
AIDS, Acquired immunodeficiency syndrome; CBC, complete blood cell count; h, hour; min, minute; PB, protein-binding; 
, half-life; UK, unknown; wk, week.
The general side effects of antimetabolite drugs include bone marrow suppression (anemia, leukopenia, thrombocytopenia), stomatitis (inflammation of the oral mucosa), nausea, vomiting, alopecia, and hepatic and renal dysfunction. Major dose-limiting toxicities may occur in the hematopoietic and gastrointestinal systems. General adverse reactions to chemotherapeutic drugs are listed in Table 37-2.
Fluorouracil
Fluorouracil (5-FU, Adrucil) is a mainstay of treatment for a variety of cancers, including those of the breast, stomach, liver, pancreas, and skin.
Herbal Alert 37-2
5-Fluorouracil
• Use cautiously with ginseng and St. John's wort (may interfere with chemotherapy). Do not use with mistletoe because it may promote cancer growth.
• Astragalus stimulates the immune system and may help speed recovery from immunosuppressive chemotherapy. Astragalus has blood clot–fighting properties and may increase risk of bleeding when given with 5-FU.
Pharmacokinetics
Fluorouracil is administered IV to treat solid tumors and topically for superficial basal cell carcinoma. Less than 10% is bound to protein, and the half-life for the IV route is 10 to 20 minutes. A small amount of the drug is excreted in the urine, and up to 80% is excreted by the lungs as carbon dioxide.
Pharmacodynamics
Fluorouracil blocks the enzyme action necessary for DNA and ribonucleic acid (RNA) synthesis. The drug has a low therapeutic index and is used alone or in combination with other anticancer drugs. Fluorouracil can cross the blood-brain barrier. Its duration of action is 30 days.
Side Effects and Adverse Reactions
The side effects of 5-FU (Adrucil) are similar to other anticancer drugs. These include anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, photosensitivity, increased skin pigmentation, rash, and erythema. Stomatitis is an early sign of toxicity and should be reported to the physician. Myelosuppression may occur 4 to 8 days after the beginning of drug therapy.
Prototype Drug Chart 37-2 presents the pharmacologic data for 5-FU.
Nursing Process
Patient-Centered Collaborative Care
Antimetabolites: Fluorouracil
Assessment
Conduct a detailed medication history, including a list of all concurrent medications, including prescriptions, over-the counter medicines, antacids, dietary supplements, vitamins, and herbal supplements to avoid drug-drug interactions.
Obtain baseline information about patient's physical status. This should include height, weight, vital signs, laboratory values (CBC, uric acid, electrolytes, hepatic and renal studies, cardiopulmonary assessment, intake and output, skin assessment, daily activities status [i.e., ability to perform ADLs], sleep-rest cycle), nutritional status, presence or absence of underlying symptoms of disease, and use of current or past medication and treatment.
Assess laboratory values at the beginning of therapy and at specified time intervals (ranging from weekly to monthly) during therapy. Drug may be withheld if red blood cell, white blood cell, or platelet counts drop below predetermined levels.
Assess renal function studies before and during drug therapy.
Assess temperature; fever may be an early sign of infection.
Obtain baseline data regarding patient's psychosocial status, including educational level, ability and desire to learn, support systems, past coping strategies, presence or absence of emotional difficulties, and self-care abilities.
Assess patient and family knowledge related to therapeutic regimen.
Nursing Diagnoses
Risk for infection related to bone marrow suppression
Risk for imbalanced nutrition, less than body requirements, related to GI side effects of chemotherapy
Acute pain related to GI side effects (mucositis/stomatitis) of chemotherapy
Risk for impaired skin integrity related to photosensitivity caused by chemotherapy
Risk for impaired perianal skin integrity related to diarrhea caused by chemotherapy
Deficient knowledge related to chemotherapeutic protocol
Risk for caregiver role strain related to cancer diagnosis, treatment, and care responsibilities
Planning
Patient blood counts will remain in the desired range.
Patient will maintain nutritional status (adequate fluid intake and output, adequate caloric intake, stable weight).
Patient will have adequate pain control.
Patient will limit exposure to sunlight.
Patient will not experience perianal skin breakdown.
Patient/family/caregiver will demonstrate understanding of chemotherapeutic protocol (dose, administration, side effects, and adverse reactions).
Nursing Interventions
Monitor IV site frequently. Extravasation produces severe pain. If this occurs, apply ice pack and notify health care provider.
Handle drug with care during preparation and administration; avoid direct skin contact with anticancer drugs. Follow protocols.
Administer antiemetic 30 to 60 minutes before drug to prevent vomiting.
Monitor fluid intake and output and nutritional intake. GI effects are common.
Assess for hyperpigmentation along the vein in which 5-FU was administered.
Maintain strict medical asepsis during dressing changes and invasive procedures.
Monitor blood counts and laboratory values.
Offer patient food and fluids that may decrease nausea (e.g., crackers, cola, ginger ale).
Encourage mouth rinses every 2 hours with normal saline.
Support good oral hygiene; brush teeth with soft toothbrush, and use waxed dental floss.
Record number and consistency of stools; monitor perineal skin condition.
Develop patient/family teaching plan on signs and symptoms of photosensitivity.
Patient Teaching
General
Advise patient to promptly report signs of infection (e.g., fever, sore throat, chills, urinary frequency; burning on urination; redness, swelling, or pain near a wound); bleeding (e.g., bleeding gums, petechiae, bruises, hematuria, blood in the stool); or signs of anemia (e.g., increased fatigue, dyspnea, orthostatic hypotension).
Teach patient to examine mouth daily and report signs of stomatitis (soreness, ulcerations, white patches in mouth). Oral hygiene several times a day is essential. If stomatitis occurs, rinse mouth with baking soda or normal saline. Use a soft toothbrush.
Advise patient not to visit anyone who has a respiratory infection. A decreased white blood cell (WBC) count puts patient at risk for acquiring an infection.
Advise patient to take year-round photosensitivity precautions. Use sunscreen when outdoors.
Emphasize protective precautions as necessary (e.g., hand washing, personal hygiene).
Advise patient to take pain medication as prescribed to relieve mouth pain related to mucositis/stomatitis.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Teach patient to avoid pregnancy for 3 to 4 months after completing antineoplastic therapy in most situations. Some sources recommend that both men and women avoid conception for 2 years after completion of treatment.
Side Effects
Advise patient about good oral hygiene with a soft toothbrush for mucositis/stomatitis; have patient use a soft toothbrush when platelet count is ≤50,000/mm3. Instruct patient to rinse mouth every 2 hours with normal saline and avoid use of commercial mouthwashes that contain alcohol.
Remind premenopausal women that they may experience amenorrhea, menstrual irregularities, or sterility. Advise male patients that they may experience impotence.
Advise patient of possible hair loss; recommend a wig, hairpiece, scarf, or turban.
Assess for use of alternative/complementary therapy that may interact with chemotherapy.
Diet
Cultural Considerations
In some cultural groups, health care decisions are made by consensus, and the family plays a key role in filtering information given to the patient. Issues related to informed consent and full disclosure of medical information may cause distress in cultural groups who place the needs of the family above the needs of the individual. Interactions should be modified based on family structure, religious values and beliefs, time orientation, cultural health practices, and verbal and nonverbal communication.
Cultural assessment tools can provide general guidelines for health care providers.
An increased incidence of hyperpigmentation has been reported in dark-skinned people. Hyperpigmentation may be seen on the skin, nails, hair, and oral mucosa. This usually disappears over time.
Evaluation
Prototype Drug Chart 37-2
Fluorouracil, 5-Fluorouracil, 5-FU
| Drug Class | Dosage |
| Antimetabolite Trade Names: Adrucil, 5-FU,Fluroplex, Efudex (topical) Pregnancy Category: D/X (topical) | A: IV: 12 mg/kg/d × 4 d; max: 800 mg/d; repeat with 6 mg/kg on days 6, 8, 10, and 12 or as indicated. Dose regimens are varied. Topical: 1%-2% sol/cream b.i.d. to head/neck lesions; 5% to other body areas |
| Contraindications | Drug-Lab-Food Interactions |
| Hypersensitivity, pregnancy, severe infection, myelosuppression, marginal nutritional status. Reduce dose in patients with impaired hepatic or renal function or those with malnutrition. | Drug: Bone marrow depressants increase chances of toxicity. Avoid live virus vaccines, which may potentiate virus replication. Increased 5-FU toxicity with concomitant use of leucovorin calcium. Metronidazole may increase 5-FU toxicity (clearance of 5-FU decreased). Increased pharmacologic effects of 5-FU when given with cimetidine (Tagamet). Thiazide diuretics increase myelosuppression. |
| Lab: May decrease albumin; may increase excretion of 5-HIAA in urine | |
| Herb: Use cautiously with ginseng, St. John's wort, and gingko biloba. Do not use with mistletoe. Topical peppermint oil and eucalyptus oil may increase absorption of topical 5-FU. Avoid simultaneous use. | |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: IV and topical: 5%-10% | Effects on blood count: |
| Distribution: PB: UK | Peak: 10-14 d |
Metabolism:  : 10-20 minExcretion: In urine and expired carbon dioxide Nadir: 10-14 d | IV: Onset: 1-9 d Peak: 9-21 d Duration: 30 dTopical: Onset: 2-3 d Peak: 2-6 wk Duration: 4-8 wk |
| Therapeutic Effects/Uses | |
| Breast, colorectal, pancreas, stomach, esophageal, and head and neck cancers. Given in combination with levamisole after surgical resection in patients with Duke's stage C colon cancer | |
| Mode of Action: Prevention of thymidine synthetase production, thereby inhibiting DNA and RNA synthesis; not phase specific | |
| Side Effects | Adverse Reactions |
| Stomatitis, nausea, vomiting, diarrhea, alopecia, rash, photosensitivity. Diarrhea may be severe. | Bone marrow suppression Life-threatening: Thrombocytopenia, myelosuppression, hemorrhage, renal failure |
5-FU, Fluorouracil; 5-HIAA, 5-hydroxyindoleacetic acid; A, adult; b.i.d., twice a day; d, day; DNA, deoxyribonucleic acid; IV, intravenous; max, maximum; min, minute; PB, protein-binding; RNA, ribonucleic acid; sol, solution; 
, half-life; UK, unknown; wk, week.
Antitumor Antibiotics
Antitumor antibiotics (bleomycin [Blenoxane], dactinomycin (actinomycin-D) [Cosmegen], daunorubicin [Cerubidine, Daunomycin], doxorubicin [Adriamycin], mitomycin [Mutamycin], Mitoxantrone [Novantrone]) inhibit protein and RNA synthesis and bind DNA, causing fragmentation. There are several types of antitumor antibiotics, including the anthracyclines and miscellaneous drugs. Except for bleomycin, which has its major effect on the G2 phase, they are classified as CCNS drugs. These antitumor antibiotics differ from one another and are used for various cancers, including leukemia and many solid tumors. Table 37-5 lists the antitumor antibiotics, uses, and considerations.
TABLE 37-5
ANTINEOPLASTICS: ANTITUMOR ANTIBIOTICS
| DRUG TYPE AND NAME | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| bleomycin (Blenoxane) | 5-20 units/m2 once a wk or 10-20 units/m2 twice a wk IV: continuous 15 units/m2/d for 4 d Intracavitary: Pleural space 50-60 units in 50-100 mL diluent |
Squamous cell carcinomas, testicular tumor (when used with vinblastine and cisplatin), and lymphomas. Low incidence of bone marrow suppression. Lifetime dose is 400 units/m2. A serious adverse reaction is anaphylaxis. Long duration of action. Pregnancy category: D; PB: 1%;  : 2-5 h |
| dactinomycin (Actinomycin D, Cosmegen) | IV: 10-15 mcg/kg/d for 5 d (every 3-4 wk) Dose varies depending on indication |
Testicular tumors, Wilms' tumor, choriocarcinoma, and rhabdomyosarcoma. Nausea and vomiting may occur during first 24 h. Long duration of action. Pregnancy category: C; PB: 80%-90%;  : 36 h |
| daunorubicin HCl (Cerubidine) | IV: 30-60 mg/m2/d for 3 d | Leukemia, Ewing's sarcoma, Wilms' tumor, neuroblastoma, and non-Hodgkin's lymphoma. Long duration of action. Pregnancy category: D; PB: 80%;  : 19 h |
| doxorubicin (Adriamycin) | See Prototype Drug Chart 37-3. | |
| epirubicin (Ellence) | IV: 100-120 mg/m2 every 3-4 wk | Cancers of breast, lung, lymph system, stomach, and ovaries. Metastatic node-positive breast cancer; adjuvant with anticancer therapy. May be used in combination therapy with cyclophosphamide and fluorouracil (CEF) for breast cancer; improved survival rate over cyclophosphamide, methotrexate, and fluorouracil (CMF). Adverse effects include bone marrow suppression, cardiotoxicity (less than doxorubicin), and extravasation necrosis. Less cardiotoxic than doxorubicin; similar efficacy. Pregnancy category: D; PB: 77%;  : 33 h |
| idarubicin (Idamycin) | IV: Induction: 12 mg/m2 slow IV push for 3 d | Acute monocytic leukemia and solid tumors. More potent than daunorubicin or doxorubicin. Vesicant, monitor CBC. Urine may be red. Pregnancy category: D; PB: 97%;  : 22 h |
| mitomycin (Mutamycin) | IV: 10 mg/m2 every 8 wk Intracavitary: Bladder: 20-40 mg in 20-40 mL of water |
Disseminated adenocarcinoma of breast, stomach, and pancreas. Also used for cancer of the head, neck, cervix, and lung. Monitor temperature and CBC. Pregnancy category: D; PB: UK;  : 12 min |
| mitoxantrone (Novantrone) | IV: For acute leukemia: Induction: 12 mg/m2/d for 3 d |
Acute nonlymphocytic leukemia; may be used for breast cancer. Rash, dyspnea, hypotension, facial swelling, blue urine, sclera, skin hue change may occur. Severe hepatic dysfunction with decreased total body clearance. Pregnancy category: D; PB: 95%;  : 1.5-13 d |
| valrubicin (Valstar) | Intravesicular: Bladder: 800 mg (in 75 mL diluent) every wk for 6 wk |
Bladder cancer. May cause urinary frequency and urgency, dysuria, hematuria, and bladder pain. Pregnancy category: UK; PB: >99%;  : UK |
Note: Chemotherapeutic doses and schedules will vary depending on protocol, body surface area (m2), age, functional status, and comorbid conditions. For a full discussion of body surface area in dosage calculation, see Chapter 14.
CBC, Complete blood cell count; d, day; h, hour; min, minute; PB, protein-binding; 
, half-life; UK, unknown; wk, week.
Adverse reactions to the antitumor antibiotics are similar to other antineoplastics and include alopecia, nausea, vomiting, stomatitis, and myelosuppression. Antitumor antibiotics are capable of causing vesication (blistering of tissue); exceptions to this are bleomycin (Blenoxane) and plicamycin (Mithracin). General adverse reactions to chemotherapeutic drugs are listed in Table 37-2.
Doxorubicin
Doxorubicin is used in the treatment of many types of cancer and is an important prototype drug that has led to the development of many analogs (e.g., epirubicin [Ellence], idarubicin [Idamycin]). However, it has severe cardiotoxic side effects and must be given with caution.
Herbal Alert 37-3
Doxorubicin
• Green tea (Camellia sinensis) may enhance antitumor effects of doxorubicin. Report use to the health care provider. Use cautiously with grapeseed (inhibits effects of doxorubicin), garlic (anticlotting properties, may decrease effects of chemotherapy), and St. John's wort (may decrease effectiveness of chemotherapy).
• Schisandra extract (Schisandra, gomishi, Sheng-Mai-San) may decrease the cardiotoxicity associated with doxorubicin. Schisandra stimulates hepatic metabolism and may interfere with doxorubicin, which is excreted through the liver.
Pharmacokinetics
Doxorubicin is administered IV and metabolized in the liver to active and inactive metabolites. The various metabolites affect the half-life; the initial phase of doxorubicin is 12 minutes, the intermediate phase is 3.5 hours, and the final phase is 30 hours.
Pharmacodynamics
Doxorubicin) is prescribed in combination with other anticancer agents for the treatment of cancers of the breast, ovaries, lung, and bladder and also for leukemias and lymphomas. A major concern for clinicians is that doxorubicin can cause cardiotoxicity. Recipients of this drug are limited to a maximum lifetime dose of 550 mg/m2. This dose may be lower for individuals who have preexisting cardiac problems, use other cardiotoxic medications, are older, or have received radiation to the chest. Prior to treatment with doxorubicin, the cardiac function of potential recipients is assessed. Dexrazoxane (Zinecard) is a cytoprotective (chemoprotective) agent that may be given to help prevent cardiotoxicity associated with doxorubicin administration.
Side Effects and Adverse Reactions
Some antitumor antibiotics can cause organ toxicities. Individuals receiving bleomycin (Blenoxane) may develop pneumonitis that progresses to pulmonary fibrosis. In addition to doxorubicin, daunorubicin (Cerubidine) and idarubicin (Idamycin) can also cause cardiotoxicity.
Prototype Drug Chart 37-3 presents the pharmacologic data for doxorubicin.
Nursing Process
Patient-Centered Collaborative Care
Antitumor Antibiotics: Doxorubicin
Assessment
Conduct a detailed medication history, including a list of all concurrent medications, including prescriptions, over-the counter medicines, antacids, dietary supplements, vitamins, and herbal supplements to avoid drug-drug interactions.
Obtain baseline information about patient's physical status. This should include height, weight, vital signs, laboratory values (CBC, uric acid, electrolytes, hepatic and renal studies, cardiopulmonary assessment, intake and output, skin assessment, daily activities status [i.e., ability to perform ADLs], sleep-rest cycle), nutritional status, presence or absence of underlying symptoms of disease, and the use of current or past medications and treatment.
Assess laboratory tests at the beginning of therapy and at specified time intervals (ranging from weekly to monthly) during therapy. Drug may be withheld if red blood cell (RBC), white blood cell (WBC), or platelet counts drop below predetermined levels.
Assess CBC, differential, and platelet count weekly. Drug may be withheld if RBC, WBC, or platelet counts drop below predetermined levels.
Conduct thorough physical assessment, and document findings.
Assess temperature; fever may be an early sign of infection.
Obtain baseline data regarding patient's psychosocial status, including educational level, ability and desire to learn, support systems, past coping strategies, presence or absence of emotional difficulties, and self-care abilities.
Assess patient's and family's knowledge related to therapeutic regimen.
Nursing Diagnoses
Risk for infection related to bone marrow suppression
Risk for decreased cardiac tissue perfusion related to cardiotoxic effects of chemotherapy
Risk for impaired skin integrity related to vesicant properties of chemotherapy
Deficient knowledge related to antineoplastic therapy
Disturbed body image related to cancer treatment
Anxiety related to cancer diagnosis and the unknown outcomes of treatment
Risk for caregiver role strain related to cancer diagnosis, treatment, and care responsibilities
Planning
Patient will maintain blood cell values in the desired range.
Patient will be free from cardiac dysfunction.
Patient's skin integrity will remain intact.
Patient/family/caregiver will demonstrate understanding of the chemotherapy regimen, including side effects.
Assess patient/family/caregiver knowledge related to chemotherapeutic protocol.
Nursing Interventions
Monitor IV site frequently. Doxorubicin is a severe vesicant whose effects are not immediately apparent. Give drug through a large-bore, quickly running IV infusion. Monitor blood counts and laboratory values.
Extravasation produces severe pain. If extravasation occurs, stop infusion immediately. Do not remove IV device from patient. Attempt to aspirate residual vesicant from IV device using a small syringe, and then remove the device. Assess the site. Notify health care provider. Apply warm packs for 15 to 20 minutes at least 4 times per day for first 24 hours. For peripheral extravasations, elevate extremity. Tissue necrosis may occur 3 to 4 weeks after infiltration into tissue.
Handle drug with care during preparation; avoid direct skin contact with drug.
Administer antiemetic 30 to 60 minutes before chemotherapy.
Monitor for changes in urine color (pink to red). The drug is red and is excreted in the urine.
Offer patient food and fluids that may decrease nausea (e.g., crackers, cola, ginger ale).
Administer prophylactic antibiotics to prevent infection.
Offer analgesics for pain as prescribed.
Maintain strict medical asepsis during dressing changes and invasive procedures.
Support good oral hygiene. Use soft toothbrush. Use waxed dental floss.
Patient Teaching
General
Teach patient the signs and symptoms of cardiac dysfunction (shortness of breath, palpitations, edema in extremities) and to report these to health care provider.
Teach patient about changes in urine color (pink or red) caused by this drug.
Advise patient to promptly report signs of infection (e.g., fever, sore throat), bleeding (e.g., bleeding gums, petechiae, bruises, hematuria, blood in stool), and anemia (e.g., increased fatigue, dyspnea, orthostatic hypotension).
Emphasize protective precautions (e.g., hand washing, personal hygiene).
Teach patient that complete alopecia occurs with doses >50 mg/m2. Teach that hair will begin to regrow within several months after therapy is completed.
Teach patient about “radiation recall” on previously irradiated skin.
Advise patient not to visit anyone who has a respiratory infection. A decreased WBC count puts patient at risk for acquiring an infection.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Teach patient to avoid pregnancy for 3 to 4 months after completing antineoplastic therapy in most situations. Some sources recommend that both men and women avoid conception for 2 years after completion of treatment.
Provide information on where to purchase cosmetic supplies (e.g., wigs) should hair loss occur.
Side Effects
Assess for nausea/vomiting, and administer antiemetics as prescribed.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Remind premenopausal women that they may experience amenorrhea, menstrual irregularities, or sterility; advise male patient that he may experience impotence.
Advise patient of possible hair loss; recommend a wig, hairpiece, scarf, or turban.
Assess for use of alternative/complementary therapies that may interact with chemotherapy agent.
Diet
Cultural Considerations
In some cultural groups, health care decisions are made by consensus, and the family plays a key role in filtering information given to the patient. Issues related to informed consent and full disclosure of medical information may cause distress in cultural groups that place the needs of the family above the needs of the individual. Interactions should be modified based on family structure, religious values and beliefs, time orientation, cultural health practices, and verbal and nonverbal communication.
Cultural assessment tools can provide general guidelines for health care providers.
Hyperpigmentation of the tongue and oral mucosa has been seen after the administration of doxorubicin in African Americans. Incidence rate of high-grade neutropenia may be higher in Asian patients.
Evaluation
Prototype Drug Chart 37-3
Doxorubicin
| Drug Class | Dosage |
| Antitumor antibiotic Trade Name: Adriamycin Pregnancy Category: D | A: 40-75 mg/m2 as a single dose every 3-4 wk or no more than 30 mg/m2 every 2 wk with 1- wk restIV for 3 d every 4 wk Safety and efficacy have not been established for children. |
| Reduce dose with renal and hepatic impairment. | |
| Contraindications | Drug-Lab-Food Interactions |
| Pregnancy, severe cardiac disease. Cardiac status and cardiac ejection fraction should be tested before starting doxorubicin therapy. Do not exceed a lifetime cumulative dose of 550 mg/m2 (450 mg/m2 if patient has had prior chest irradiation or is receiving cyclophosphamide). Dexrazoxane (Zinecard) is used to help prevent or lessen cardiac damage. Caution: Hepatic and renal impairment | Drug: Calcium channel blockers, paclitaxel (Taxol), and mitomycin increase risk of cardiotoxicity if given with doxorubicin. Doxorubicin may decrease digoxin levels. Doxorubicin decreases levels of phenytoin. Cyclophosphamide (Cytoxan) increases risk of cardiotoxicity and hemorrhage. Increased risk of hepatotoxicity when given with mercaptopurine. Increased plasma clearance of doxorubicin when given with barbiturates. Precipitate will form when doxorubicin is combined with heparin or 5-FU. Decreased metabolic clearance of 5-FU (Adrucil) and increased cytotoxicity when given with alfa interferon. Prolonged hemotoxic effects may occur if doxorubicin and cyclosporine are given together. Do not give with zidovudine (Retrovir), as it may decrease effectiveness of doxorubicin. |
| Lab: ECG changes. Increases uric acid. | |
| Herb: Green tea may enhance antitumor effects. Report use to health care provider. Use cautiously with grapeseed, garlic, St. John's wort. | |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: IV Distribution: PB: 80%-90% Metabolism:  : 3-30 hExcretion: 40% in bile and 5% in urine Nadir: 10-14 d (doxorubicin) | IV: Onset: 7-10 d Peak: 14 d Duration: 21 d |
| Therapeutic Effects/Uses | |
| Breast, bladder, ovarian, and lung cancers; leukemias; lymphomas, soft-tissue and bone sarcoma | |
| Mode of Action: Inhibits DNA and RNA synthesis; has immunosuppressant activity | |
| Side Effects | Adverse Reactions |
| Stomatitis, anorexia, nausea, vomiting, diarrhea, rash, alopecia. Doxorubicin is a potent vesicant. May cause a flare reaction. Nausea and vomiting are dose-related and may begin 1-3 h after administration. Causes discolored urine (pink to red) for up to 48 h. May cause “radiation recall” to previously irradiated skin. | Esophagitis; anemia; hyperpigmentation of nails, tongue, and oral mucosa, especially in African Americans. Teratogenic, mutagenic, and carcinogenic. Life-threatening: Thrombocytopenia, leukopenia, cardiotoxicity, congestive heart failure, electrocardiogram changes, severe myelosuppression, anaphylaxis |
5-FU, Fluorouracil; d, day; DNA, deoxyribonucleic acid; ECG, electrocardiogram; h, hour; IV, intravenous; PB, protein-binding; RNA, ribonucleic acid; 
, half-life; wk, week.
Plant Alkaloids
Plant alkaloids are derived from natural products that are CCS and block cell division at the M phase of the cell cycle. The vinca alkaloids (e.g., vinblastine [Velban], vincristine [Oncovin], and vinorelbine [Navelbine]) are obtained from the periwinkle plant. The antimicrotubules or taxanes group (e.g., docetaxel [Taxotere] and paclitaxel [Taxol]) were originally procured from the needles and bark of the yew tree, which only grows in the Pacific Northwest. Due to the scarcity of this natural resource, a semisynthetic form of paclitaxel was developed and then approved by the FDA. Docetaxel (Taxotere) is a semisynthetic analogue of paclitaxel. The podophyllotoxins (e.g., etoposide [VP-16, Pepesid], teniposide [VP26, Vumon]) and camptothecan analogues (e.g., Irinotecan [Camptosar, CPT-11], Topotecan [Hycamtin]) interfere with the action of topoisomerase enzymes, causing apoptosis in cancer cells. A few retinoid derivatives (e.g., bexarotene [Targretin], thalidomide [Thalomid]) play a limited role in treating cancer as well. Table 37-6 lists the plant alkaloids and their uses and considerations.
TABLE 37-6
ANTINEOPLASTICS: PLANT ALKALOIDS
| DRUG TYPE AND NAME | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Vinca Alkaloids | ||
| vinblastine (Velban) | IV: 1.5-2.0 mg/m2/d continuous infusion for 5 d | Cancers of the testes, breast, and kidney and treatment of lymphomas, lymphosarcomas, and neuroblastomas. Nausea, vomiting, and alopecia are common side effects. Check CBC before dosing. Pregnancy category: D; PB: 75%;  : 25 h |
| vincristine (Oncovin) | IV: 0.4-1.4 mg/m2/wk | Cancer of the breast, lungs, and cervix; multiple myelomas, sarcomas, lymphomas, Wilms' tumor. Assess neurologic difficulties. Used for treating Hodgkin's disease in combination therapy, MOPP (mechlorethamine, vincristine, procarbazine, and prednisone). Do not give intrathecally. Pregnancy category: D; PB: 75%;  : triphasic 2-85 h (see Prototype Drug Chart 37-4) |
| vinorelbine (Navelbine) | IV: 30 mg/m2/wk | First-line treatment for ambulatory patients with advanced, unresectable non–small-cell lung cancer (NSCLC). May be used alone or in combination with cisplatin for stage IV NSCLC and in combination with cisplatin for stage III NSCLC. Pregnancy category: D; PB: UK;  : 27-43 h |
| Antimicrotubules/Taxanes | ||
| docetaxel (Taxotere) | IV: 60-100 mg/m2 over 1-h infusion every 3 wk | Advanced or metastatic breast cancer. Inhibits mitosis in cells. Greater antitumor activity with lower toxicity effect than paclitaxel (Taxol). Monitor WBC and platelet count; if low, dose may need to be decreased. Pregnancy category: D; PB: UK;  : 11 h |
| paclitaxel (Taxol) | IV: For breast cancer: 175 mg/m2 over 3-h infusion every 3 wk For ovarian cancer: 135-175 mg/m2 over 24-h infusion |
Metastatic ovarian and breast cancer. Monitor vital signs and electrocardiogram. Long duration of action (3 wk). Peak action is 11 d. Pregnancy category: D; PB: 80%-90%;  : 5-17 h |
| Podophyllotoxins | ||
| etoposide (VP-16, Vepesid) | IV: For testicular cancer: 50-100 mg/m2/d for 5 d For small-cell lung cancer 75-200 mg/m2/d for 3 d |
Testicular cancer, small-cell lung cancer. Give by slow IV infusion (30-60 min), as hypotension is a side effect of rapid infusion. Bone marrow suppression is a dose-limiting toxicity; Pregnancy category: D; PB: wide variation;  : 6-12 h |
| teniposide (VM-26, Vumon) | IV: 100 mg/m2/wk for 6-8 wk OR 50 mg/m2 twice weekly for 4 wk | Acute lymphocytic leukemia, neuroblastoma, non-Hodgkin's lymphoma. Give by slow IV infusion (30-60 min), as hypotension is a side effect of rapid infusion. Pregnancy category: D; PB > 95%;  : 5 h |
| Camptothecan Analogs | ||
| irinotecan (Camptosar, CPT-11) | IV: 180 mg/m2 over 90 min | Colon and rectal cancer. Can cause early (during administration or within 24 h) and late diarrhea. Pretreatment bowel function (without an antidiarrheal medication) should be maintained for at least 24 h before next dose of chemotherapy is given. Pregnancy category: D; PB > 90%;  : 6 h |
| topotecan (Hycamtin) | IV: For ovarian cancer and SCLC: 1.5 mg/m2/d infusion over 30 min for 5 d every 21 d For relapsed SCLC: PO: 2.3 mg/m2/d for 5 d |
Ovarian cancer, small-cell lung cancer. GI toxicities (nausea, vomiting, diarrhea common). Bone marrow suppression a dose-limiting toxicity. Pregnancy category: D; PB >35%;  : 2-3 h |
| Retinoids | ||
| bexarotene (Targretin) | PO: 300 mg/m2/d for 97 wk | Cutaneous T-cell lymphoma. Associated with birth defects in humans. Do not administer to pregnant patients. Pregnancy category: X; PB >99%;  : 7 h |
| thalidomide (Thalomid) | PO: 200 mg/d | Multiple myeloma and skin lesions related to erythema nodosum leprosum. Banned by FDA in the 1960s for causing birth defects. NEVER give to pregnant patients. Pregnancy category: X; PB 55%-65%;  : 5-7 h |
Note: Chemotherapeutic doses and schedules will vary depending on protocol, body surface area (m2), age, functional status, and comorbid conditions. For a full discussion of body surface area in dosage calculation, see Chapter 14.
CBC, Complete blood cell count; d, day; h, hour; PB, protein-binding; 
, half-life; UK, unknown; WBC, white blood cell; wk, week.
Adverse reactions to plant alkaloids include leukopenia, hypersensitivity reactions, partial-to-complete alopecia, constipation, nausea, vomiting, diarrhea, and phlebitis. The plant alkaloids damage peripheral nerve fibers and may cause reversible or irreversible neurotoxicity. Signs and symptoms of neurotoxicity include a decrease in muscular strength, numbness, tingling of fingers and toes (“stocking/glove” syndrome), constipation, and motor instability. Other adverse effects of these drugs include loss of deep tendon reflexes, muscle weakness, joint pain, and bone marrow suppression. Docetaxel may cause fluid retention. General adverse reactions to chemotherapeutic drugs are listed in Table 37-2.
Vincristine
Vincristine (Oncovin), developed from the periwinkle plant, was originally approved by the FDA in the 1960s to treat Wilms' tumor in children.
Herbal Alert 37-4
Vincristine
• Use cautiously with bromelain (an extract from the pineapple plant), which may improve the efficacy of vincristine. Catharanthus roseus (periwinkle) may increase risk of bone marrow suppression when given with vincristine. Schisandra extract (Schisandra, gomishi, Sheng-Mai-San) stimulates hepatic metabolism and may interfere with vincristine, which is excreted through the liver.
Pharmacokinetics
Vincristine is given IV. Its half-life is between 19 and 155 hours, and it is primarily (~75%) protein-bound. The drug is extensively metabolized by the liver.
Pharmacodynamics
Vincristine is used in chemotherapy protocols to treat acute and chronic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, sarcoma, Wilms' tumor, breast cancer, and lung cancer. The onset of action begins in a few minutes; however, the therapeutic effect may take several days. Vincristine is an anticancer drug that is only administered IV.
Side Effects and Adverse Reactions
Several drug interactions may occur with vincristine (Oncovin). The patient should report all medications that he or she is taking, including OTC medicines and herbal supplements. Serious drug interactions can occur when taking vincristine (Oncovin) and L-asparaginase (Elspar), the cardiac medication digoxin (Lanoxin), phenobarbital (Solfoton), calcium channel blockers, and mitomycin (Mutamycin).
Nursing Process
Patient-Centered Collaborative Care
Plant Alkaloids: Vincristine
Assessment
Conduct a detailed medication history, including a list of all concurrent medications, including prescriptions, over-the counter medicines, antacids, dietary supplements, vitamins, and herbal supplements to avoid drug-drug interactions.
Obtain baseline information about patient's physical status. This should include height, weight, vital signs, laboratory values (CBC, uric acid, electrolytes, hepatic and renal studies, cardiopulmonary assessment, intake and output, skin assessment, daily activities status [i.e., ability to perform ADLs], sleep-rest cycle), nutritional status, presence or absence of underlying symptoms of disease, and the use of current or past medications and treatment.
Assess laboratory results at the beginning of therapy and at specified time intervals (ranging from weekly to monthly) during therapy. Drug may be withheld if red blood cell, white blood cell, or platelet counts drop below predetermined levels.
Assess CBC, differential, and platelet count weekly.
Monitor bilirubin levels. Dose may be reduced if bilirubin levels are >1.5 mg/dL.
Conduct a thorough physical assessment, and document findings. Be especially aware of evidence of neurotoxicity, because this is a dose-limiting toxicity.
Assess for signs of peripheral neuropathy (numbness or tingling in fingers or toes), loss of deep tendon reflexes, foot drop, slapping gait, and difficulty walking.
Monitor bowel function. Autonomic neuropathy may lead to constipation and paralytic ileus. The use of vincristine and narcotic analgesics may increase the risk of constipation.
Assess temperature; fever may be an early sign of infection.
Monitor for acute bronchospasm.
Obtain baseline data regarding patient's psychosocial status, including educational level, ability and desire to learn, support systems, past coping strategies, presence or absence of emotional difficulties, and self-care abilities.
Assess patient and family knowledge related to therapeutic regimen.
Nursing Diagnoses
Planning
Patient will maintain blood cell values in the desired range.
Patient will maintain adequate bowel function.
Patient will be free from neuropathic dysfunction.
Patient will be free from respiratory complications (bronchospasm).
Patient/family/caregiver will demonstrate understanding of the chemotherapy regimen, including side effects.
Nursing Interventions
Assess for signs of respiratory distress during and after administration.
Monitor for signs of peripheral neuropathy (numbness and/or tingling in hands and/or feet, sensory loss, loss of deep tendon reflexes, paresthesia, foot drop, wrist drop, ataxia).
Assess IV site carefully. Vincristine is a severe vesicant whose effects are not immediately apparent. Give drug through a large-bore, quickly running IV infusion. Monitor blood counts and laboratory values.
Extravasation produces severe pain. If extravasation occurs, stop infusion immediately. Do not remove IV device from the patient. Attempt to aspirate residual vesicant from the IV device using a small syringe, and then remove the IV device. Assess the site. Notify health care provider. Apply warm packs for 15 to 20 minutes at least 4 times per day for first 24 hours. For peripheral extravasations, elevate extremity. Tissue necrosis may occur 3 to 4 weeks after infiltration into tissue.
Administer antiemetic 30 to 60 minutes before chemotherapy, or as prescribed.
Administer stool softener or laxative as prescribed.
Monitor fluid intake and output, and nutritional intake.
Maintain strict medical asepsis during dressing changes and invasive procedures.
Patient Teaching
General
Advise patient to promptly report signs of infection (e.g., fever, sore throat), bleeding (e.g., bleeding gums, petechiae, bruises, hematuria, blood in the stool), and anemia (e.g., increased fatigue, dyspnea, orthostatic hypotension).
Teach patient the signs and symptoms of neurotoxicity (numbness and/or tingling in hands and/or feet, sensory loss, loss of deep tendon reflexes, paresthesia, foot drop, wrist drop, ataxia). Inability to button clothes or to close zippers may be an early sign of peripheral neuropathy.
Emphasize protective precautions (e.g., hand washing, personal hygiene) as necessary.
Advise patient not to visit anyone who has a respiratory infection. A decreased WBC count puts patient at risk for acquiring an infection.
Teach patient signs of “stocking/glove” syndrome (numbness/tingling of hands and feet). This may last as long as 1 year or may never completely resolve.
Teach patient that complete alopecia may occur. Teach patient that hair will begin to regrow within several months after therapy is completed.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Teach patient that in most situations pregnancy should be avoided for 3 to 4 months after completing antineoplastic therapy. Some sources recommend that both men and women avoid conception for 2 years after completion of treatment.
Side Effects
Teach patient the signs of peripheral neuropathy.
Teach patient to report constipation and abdominal pain.
Assess for nausea and vomiting; administer antiemetics as prescribed.
Advise patient of possible hair loss; recommend a wig, hairpiece, scarf, or turban.
Teach importance of using birth-control measures as appropriate. Discuss sperm banking with male patients as appropriate.
Remind premenopausal women that they may experience amenorrhea, menstrual irregularities, or sterility; advise male patient that he may experience impotence.
Assess for use of alternative/complementary therapy that may interact with chemotherapy agent.
Teach patient the signs of tissue extravasation, which can occur 3 to 4 weeks after administration of the drug.
Diet
Cultural Considerations
In some cultural groups, health care decisions are made by consensus, and the family plays a key role in filtering information given to the patient. Issues related to informed consent and full disclosure of medical information may cause distress in cultural groups that place the needs of the family above the needs of the individual. Interactions should be modified based on family structure, religious values and beliefs, time orientation, cultural health practices, and verbal and nonverbal communication.
Cultural assessment tools can provide general guidelines for health care providers.
Evaluation
Targeted Therapies
Chapter 38 provides in-depth information on this treatment modality.
Liposomal Chemotherapy
A more recent change in the delivery of chemotherapy involves the use of anticancer drugs that have been packaged inside synthetic fat globules called liposomes. The fatty coating helps the chemotherapy drug remain in the system longer, decreases side effects (e.g., hair loss, nausea, cardiotoxicity), and increases the duration of therapeutic effects. Encapsulated forms of doxorubicin (Doxil, Caelyx, Myocet), daunorubicin (DaunoXome), and Cytarabine (DepoCyt) are examples of liposomal chemotherapy.
Hormonal Agents
Although hormones are not considered true chemotherapeutic agents, several classes of hormonal agents are used in the treatment of cancer. These include corticosteroids, sex hormones, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone analogues, and antiandrogens.
Corticosteroids
Corticosteroids (glucocorticoids) are antiinflammatory agents that suppress the inflammatory process that is associated with tumor growth. Although the exact mechanism of action is unknown, these agents may block steroid-specific receptors on the surface of cells. This blocking action slows the growth fraction of the tumor, thus retarding its growth. Prednisone (Cordrol, Deltasone), dexamethasone (Cortastat, Dalalone), and hydrocortisone (Hydrocortone, Solu-Cortef) can help decrease cerebral edema caused by a malignant brain tumor. Cortisone drugs give the patient a sense of well-being and varying degrees of euphoria. Cortisone derivatives taken internally produce many adverse side effects, including fluid retention, potassium loss, increased risk for infection, increase in blood sugar, increased fat distribution, muscle weakness, increased bleeding tendency, and euphoria.
Sex Hormones
The sex hormones (e.g., estrogen, androgen) or hormone-like agents are used to slow the growth of hormone-dependent tumors (e.g., prostate cancer, breast cancer). Estrogen therapy is a palliative treatment used to decrease the progression of prostatic cancer in men and to slow the growth of hormone-dependent breast cancer in women. Estrogen preparations suppress tumor growth and may induce remission of the cancer for up to 1 year. Examples of this group of drugs are diethylstilbestrol (Stilbestrol), ethinyl estradiol (Estinyl), chlorotrianisene (TACE), and conjugated estrogens (Premarin).
Progestins may be prescribed to treat breast cancer, endometrial carcinoma, and renal cancer. These drugs (e.g., hydroxyprogesterone caproate [Duralutin]), medroxyprogesterone acetate [Depo-Provera], and megestrol acetate [Megace]) act by shrinking the cancer tissues. Adverse reactions include fluid retention and thrombotic (clot) disorders.
Androgens are given to treat advanced breast cancer in premenopausal women. This male hormone promotes regression of tumors. If androgen therapy is used over a long period of time, masculine secondary sexual characteristics, such as body hair growth, lowering of the voice, and muscle growth, will occur. Antiestrogens such as tamoxifen (Nolvadex) and fulvestrant (Faslodex) are used to treat breast cancer tumors that are estrogen-receptor positive (ER+). Tamoxifen has shown proven efficacy in preventing tumor recurrence in both premenopausal and postmenopausal women, but it has a number of side effects associated with it. These include hot flashes, irregular menses, fatigue, headaches, nausea, and vomiting. Men who take tamoxifen may experience headaches, impotence, and a decreased interest in sexual activity. Tamoxifen increases a woman's risk for developing cancer of the uterus.
Selective estrogen receptor modulators (SERMs) act like antiestrogens to slow tumor growth, but have fewer side effects than tamoxifen. SERM drugs currently in use include raloxifene (Evista) and toremifene (Fareston). A new generation of SERM drugs is currently being evaluated to determine effects on preventing recurrent breast cancer, decreasing postmenopausal bone loss, and reducing the risk of cardiovascular disease.
Prototype Drug Chart 37-4 details the pharmacologic behavior of vincristine (Oncovin).
Prototype Drug Chart 37-4
Vincristine
| Drug Class | Dosage |
| Plant alkaloid/vinca alkaloid Trade Name: Oncovin Pregnancy Category: D | A: IV: use only via free-flowing IV catheter. 0.4-1.4 mg/m2 weekly. A 50% reduction in the dose recommended for those with a direct serum bilirubin value above 3 mg/100 mL C: IV: use only via free-flowing IV catheter. 2 mg/m2 For children <10 kg, starting dose is 0.05 mg/kg weekly If peripheral neuropathies occur, reduction or discontinuance of therapy may be needed. |
| Contraindications | Drug-Lab-Food Interactions |
| FATAL if given intrathecally Do not give to patients receiving radiation therapy through ports into the liver. Hypersensitivity Do not give to patients with Charcot-Marie-Tooth syndrome. Caution: Pregnancy, liver or kidney disease, neuromuscular disease, or infection | Drug: Acute life-threatening bronchospasm may occur, especially if drug is given with mitomycin (Mutamycin). L-asparaginase (Elspar) may reduce hepatic clearance of vincristine. Vincristine decreases digoxin effects. Monitor digoxin levels. Vincristine decreases phenytoin effects. Monitor patient for seizure activity. Do not dilute in solutions that increase or decrease pH outside a range of 3.5-5.5. Mix only with normal saline or glucose in water. Herb: Use cautiously with bromelain (pineapple extract). Catharanthus roseus (periwinkle) may increase risk of bone marrow suppression when given with vincristine. Lab: May cause hyponatremia, hyperuricemia, anemia, leukopenia, thrombocytopenia. |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: IV | Effects on blood count: Decreased |
| Distribution: PB: 75% Metabolism: Liver  : first phase, 5 min; second phase,  h; terminal phase, 85 h | IV: Onset: 7 d Peak: 10-14 d Duration: 21 d |
| Excretion: 80% in feces; 10%-20% in urine | |
| Nadir: 7-10 d | |
| Therapeutic Effects/Uses | |
| Acute leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, Wilms' tumor, multiple myeloma, acute and chronic leukemia, breast and lung cancers | |
| Mode of Action: Affects cells in the M phase of the cell cycle, and inhibits mitosis | |
| Side Effects | Adverse Reactions |
| Peripheral neuropathy, loss of deep tendon reflexes, phlebitis, constipation, cramps, nausea, vomiting, muscle weakness, reversible alopecia | Sensory loss, hypotension, visual disturbances, ptosis, ileus, SIADH, hyponatremia, hyperuricemia, severe local reaction with extravasation, fever Life-threatening: intestinal necrosis, seizures, coma, acute bronchospasm, bone marrow suppression |
d, Day; h, hour; IV, intravenous; PB, protein-binding; SIADH, syndrome of inappropriate antidiuretic hormone secretion; 
, half-life; ≤, less than or equal to.
Gonadotropin-Releasing Hormone Analogues
Luteinizing hormone-releasing hormone (LH-RH) agonists (e.g., leuprolide [Lupron], goserelin [Zoladex]) suppress the secretion of follicle-stimulating hormone and luteinizing hormone from the pituitary gland. Initially an increase in testosterone levels is seen. However, with continued use the pituitary gland becomes insensitive to this stimulation, leading to a reduction in the production of androgens and estrogens.
Antiandrogens
Antiandrogens (e.g., flutamide [Eulexin], nilutamide [Nilandron], bicalutamide [Casodex]) are useful in treating men with hormone-responsive prostate cancer that has metastasized. These agents work by binding to androgen receptors and blocking the effects of dihydrotestosterone on the prostate cancer cells.
Aromatase Inhibitors
In postmenopausal women, the ovaries no longer produce estrogen, but androgen is converted to estrogen in this group of women. The aromatase inhibitors block the peripheral conversion of androgens to estrogens, thus suppressing the postmenopausal synthesis of estrogen and slowing tumor growth. Aromatase inhibitors are used in the treatment of hormonally sensitive breast cancer in postmenopausal women or premenopausal women who have had their ovaries removed. Anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are examples of aromatase inhibitors currently in use. Increasingly these agents are being used before tamoxifen in postmenopausal women with hormonally responsive metastatic breast cancer. Table 37-7 lists hormonal agents, uses, and considerations.
TABLE 37-7
ANTINEOPLASTICS: HORMONES, HORMONE ANTAGONISTS, AND MISCELLANEOUS
| DRUG TYPE AND NAME | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Androgens | ||
| testolactone (Teslac) | PO: 250 mg 4 times/d | Palliative treatment of breast carcinoma in postmenopausal women. Monitor serum calcium levels. Voice may deepen, and facial hair may increase. Pregnancy category: D; PB: UK;  : UK |
| Hormonal Antagonists | ||
| aminoglutethimide (Cytadren) | PO: 750-2000 mg/d in divided doses | Adrenal carcinoma, ectopic adrenocorticotropic hormone (ACTH)-producing tumors. Suppresses adrenal activity. May be used in breast cancer therapy. Treatment typically lasts for 3 mo. Pregnancy category: D; PB: 20%-25%;  : 7-15 h |
| anastrozole (Arimidex) bicalutamide (Casodex) | PO: anastrozole 1 mg/d bicalutamide 50 mg/d |
Advanced breast cancer in postmenopausal women. Diarrhea, headache, hot flashes, pain, hypertension, and dyspnea might occur. Pregnancy category: D; PB: 40%;  : 50 h |
| exemestane (Aromasin) | PO: 25 mg/d | Advanced metastatic prostatic carcinoma. Pregnancy category: X; PB: UK;  : 5.8 d |
| flutamide (Eulexin) | PO: 250 mg every 8 h | Advanced breast cancer in postmenopausal women. Prostatic cancer. Pregnancy category: D; PB: UK;  : 24 h |
| fulvestrant (Faslodex) | IM: 500 mg as 2 5-mL injections, one in each buttock on days 1, 15, and 29 and once monthly thereafter | Metastatic prostatic carcinoma, usually in combination with other anticancer drugs. Pregnancy category: D; PB: 95%;  : 5-10 h |
| goserelin acetate (Zoladex) | subQ: 3.6 mg/mo in upper abdominal wall every 28 d | Treatment of hormone-receptor positive metastatic breast cancer in postmenopausal women whose disease has progressed after antiestrogen therapy. Pregnancy category: D; PB: 99%;  : 40 d |
| histrelin acetate implant (Vantas) | SubQ implant: 50 mg implanted under skin on upper, inner arm, every 12 months (remove old implant before placing new one) | Treatment of advanced prostate cancer. A small, thin implant is placed under the skin of the arm. Drug works for 12 mo, and then implant needs to be replaced. Pregnancy category: X; PB: 70%;  : 3 h |
| letrozole (Femara) | PO: 2.5 mg/d | Metastatic prostatic carcinoma. Drug is a synthetic luteinizing hormone-releasing analogue. May also be used in breast cancer and endometriosis. Gynecomastia, breast swelling, and hot flashes may occur. Pregnancy category: X; PB: UK;  : 4-6 h |
| leuprolide (Lupron, Viadur) | IM: Depot suspension 7.5 mg every mo Viadur implant 65 mg every 12 mo subQ: 1 mg/d |
Advanced breast cancer in postmenopausal women. Decreases estrogen biosynthesis. May be more effective than megestrol acetate and aminoglutethimide. Pregnancy category: UK; PB: UK;  : 2 dUsed to slow the growth of prostate cancer. Can be given daily (Lupron) or at 3- or 4-mo intervals (Lupron Depot). May be used to treat endometriosis. Hypersensitivity reactions may occur in people with allergy to benzyl alcohol. Pregnant patients should not take this drug (high risk of fetal damage). Pregnancy category: X; PB: 49%;  : 3 h |
| megestrol acetate (Megace) | PO: 800 mg/d | Palliative treatment of advanced carcinoma of breast and endometrium. May Promote weight gain by increasing appetite. Pregnancy category: X; PB: UK;  : 15-20 h |
| mitotane (Lysodren) | PO: 2-16 g/d | Palliative treatment of inoperable adrenal cortical carcinoma. Adverse reactions include hemorrhagic cystitis, hypouricemia, and hypercholesterolemia. Monitor vital signs. Pregnancy category: C; PB: UK;  : 20-160 d |
| nilutamide (Nilandron) | PO: 300 mg/d for 30 d, then maintenance dose | Prostatic carcinoma. Loss of libido and sexual potency may occur. Monitor liver function. Pregnancy category: C: PB: UK:  : 24-72 h |
| tamoxifen citrate (Nolvadex) | PO: 20 mg/d | Palliative treatment of advanced breast carcinoma with positive lymph nodes in postmenopausal women. Competes with estradiol at estrogen receptor sites. Decreases DNA synthesis. Reduces risk of breast cancer in postmenopausal women. Pregnancy category: D; PB: UK;  : 7 d |
| raloxifene (Evista) | PO: 60 mg daily | Selective estrogen receptor modulator (SERM) originally approved to fight osteoporosis in postmenopausal women. Reduces risk of breast cancer with fewer side effects than tamoxifen. Pregnancy category: X; PB: 95%;  : 27 h |
| toremifene citrate (Fareston) | PO: 60 mg/d | Advanced breast cancer in postmenopausal women. An antiestrogen drug. Pregnancy category: D; PB: >99%;  : 5 d |
| Miscellaneous Enzymes | ||
| asparaginase (Elspar, L-asparaginase) | IV: For leukemia induction: 200 units/kg/d for 28 d |
Acute lymphocytic leukemia. Used in combination with another anticancer drug. Common side effects include nausea, vomiting, anorexia, leukopenia, and impaired pancreatic function. Pregnancy category: C; PB: 30%;  : 8-30 h (IV) |
| pegaspargase (Oncaspar) | Teenagers up to 21 years of age: 2500 units/m2 every 14 d C: BSA 0.6 m 2500 units/m every 14 d |
Acute lymphoblastic leukemia. CCS agent that affects G1 phase of cell cycle. Interferes with DNA, RNA, and protein synthesis. Pregnancy category: C; PB: UK;  : 1.4-5.2 d |
| Vaccines | ||
| Hepatitis B (Engerix-B, Recombivax HB) | IM: given in a series of 3 doses: 0, 1, and 3 mo | First anticancer vaccine. Prevents hepatitis B and its serious consequences such as hepatocellular carcinoma (liver cancer). |
| Gardasil (quadrivalent human papillomavirus [types 6, 11, 16, 18] recombinant vaccine) | IM: 0.5 mL given in a series of 3 shots (0, 2, and 6 mo) in deltoid region of upper arm | For vaccination of women 9 to 26 years of age for prevention of diseases caused by human papillomavirus (HPV) types 6, 11 (genital warts), 16, and 18 (cervical cancer). |
| Cervarix | IM: 0.5 mL given in a series of 3 shots (0, 1, and 6 mo) in deltoid region of upper arm | For prevention of cervical cancer and precancerous lesions associated with most common cancer-causing HPV types. |
Note: Chemotherapeutic doses and schedules will vary depending on protocol, body surface area (m2), age, functional status, and comorbid conditions. For a full discussion of body surface area in dosage calculation, see Chapter 14.
CCS, Cell cycle–specific; d, day; DNA, deoxyribonucleic acid; h, hour; IV, intravenous; min, minute; mo, month; PB, protein-binding; RNA, ribonucleic acid; 
, half-life; UK, unknown; wk, week; >, greater than.
Miscellaneous Chemotherapy Agents
This category includes a number of antineoplastic agents in which the mechanism of action is unclear. Table 37-7 describes two: asparaginase (Elspar) and pegaspargase (Oncaspar).
Vaccines
Vaccines used to prevent cancer include the hepatitis B vaccine, given to prevent infection with the hepatitis B virus, which can cause liver cancer. Two recombinant vaccines, Gardasil and Cervarix, are given to girls and young women 9 to 26 years of age to prevent HPV infections that can cause cervical cancer. Cervarix is used for boys and young men 9 to 26 years of age to prevent HPV types 6 and 11, which can cause genital warts. Several experimental vaccines have shown promise in the treatment of prostate cancer.
Key Websites
Agency for Healthcare Research and Quality: www.ahrq.gov
National Cancer Institute: www.nci.nih.gov/cancertopics/chemotherapy-and-you
Oncology Nursing Society: www.ons.org/ClinicalResources
Critical Thinking Case Study
A 63-year-old patient, recently diagnosed with breast cancer, is scheduled to receive combination chemotherapy consisting of IV fluorouracil (5-FU, Adrucil), doxorubicin (Adriamycin), and cyclophosphamide (Cytoxan). This therapy is designated by the acronym FAC (fluorouracil, Adriamycin, cyclophosphamide). The patient's treatment regimen consists of the following: fluorouracil, 500 mg/m2 IV, Day 1; doxorubicin 50 mg/m2 IV, Day 1; cyclophosphamide, 500 mg/m2 IV, Day 1. This cycle is to be repeated every 21 days for 6 cycles.
1. Differentiate the drug actions of fluorouracil, doxorubicin, and cyclophosphamide.
2. What side effects and adverse reactions should the nurse assess for during therapy? Why would assessment of the cardiac, GI, and genitourinary systems be important with this drug regimen?
3. What is the maximum lifetime dose for doxorubicin? Why is this so important?
4. Describe the early signs of cardiotoxicity that might be seen days to months after the administration of doxorubicin.
5. Briefly explain why hydration would be important during this drug regimen.
6. What nursing interventions would be appropriate when caring for this patient?
7. Describe the teaching that the nurse would provide to the patient and her family.
8. After two cycles of chemotherapy, the patient complains that her mouth feels sore and that it hurts to eat. Which chemotherapy agent is most likely responsible for this finding? What nursing interventions would be initiated to address this problem?
9. Analyze protective measures necessary to avoid accidental exposure to chemotherapy agents during administration.
10. The patient calls the outpatient oncology clinic and tells the nurse that she has a temperature of 101° F (38.3° C). What actions should the nurse take to address this issue?