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Chapter 46
Antineoplastic Drugs Part 2: Cell Cycle–Nonspecific Drugs and Miscellaneous Drugs
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2. Cancer Drugs: Antineoplastic Medications
Cell cycle–nonspecific (CCNS) antineoplastic drugs
Alkylating drugs
Cytotoxic antibiotics
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Alkylating Drugs
Classic alkylators (nitrogen mustards)
Nitrosoureas
Miscellaneous alkylators
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4. Alkylating Drugs: Mechanism of Action
Work by preventing cancer cells from reproducing
Alter the chemical structure of the cells’ deoxyribonucleic acid (DNA)
Bifunctional or polyfunctional
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5. Organization of DNA and Site of Action of Alkylating Drugs
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6. Alkylating Drugs: Indications
Used in combination with other drugs to treat various types of cancer, such as:
Recurrent ovarian cancer
Brain tumors
Lymphomas
Leukemias
Breast cancer
Bladder cancer
Others
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7. Alkylating Drugs: Adverse Effects
Dose-limiting adverse effects
Nausea and vomiting, myelosuppression
Alopecia
Nephrotoxicity, peripheral neuropathy, ototoxicity
Hydration can prevent nephrotoxicity.
Extravasation causes tissue damage and necrosis.
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8. Alkylating Drugs: Examples
Cisplatin (Platinol)
Cyclophosphamide (Cytoxan)
Mechlorethamine (Mustargen, nitrogen mustard)
Others
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9. Cytotoxic Antibiotics
Natural substances produced by the mold Streptomyces
Semisynthetic substances also used
Bone marrow suppression: common toxicity
Bleomycin: instead causes pulmonary toxicity
Daunorubicin: heart failure
Doxorubicin: left ventricular failure
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10. Cytotoxic Antibiotics: Mechanism of Action
CCNS drugs are active in all phases of the cell cycle.
Act by intercalation, resulting in blockade of DNA synthesis
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11. Cytotoxic Antibiotics: Indications
Used in combination chemotherapy regimens
Used to treat a variety of solid tumors and some hematologic malignancies
Leukemia, ovarian, breast, bone, others
Squamous cell carcinomas
AIDS-related Kaposi’s sarcoma (when intolerant to other treatments)
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12. Cytotoxic Antibiotics: Adverse Effects
All can produce bone marrow suppression, except bleomycin
Hair loss, nausea and vomiting, myelosuppression
Heart failure (daunorubicin)
Acute left ventricular failure (doxorubicin)
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13. Cytotoxic Antibiotics: Adverse Effects (Cont.)
Pulmonary fibrosis and pneumonitis (bleomycin)
Liver, kidney, and cardiovascular toxicities
Many others
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14. Cytotoxic Antibiotics: Adverse Effects (Cont.)
Cardiomyopathy is associated with large amounts of doxorubicin.
Routine monitoring of cardiac ejection fraction with multiple-gated acquisition (MUGA) scans
Cumulative dose limitations
Cytoprotective drugs such as dexrazoxane can decrease the incidence of this devastating toxicity.
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15. Audience Response System Question
Which cytotoxic antibiotic does the nurse identify as most likely to cause pulmonary fibrosis?
plicamycin
mitoxantrone
mitomycin
bleomycin
Correct answer: D
Rationale: Bleomycin is most likely to cause pulmonary fibrosis and pneumonitis. Plicamycin is most likely to cause tissue damage in the event of extravasation. Mitoxantrone is most likely to cause cardiovascular toxicity, and mitomycin is most likely to cause liver, kidney, and lung toxicities.
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16. Miscellaneous Antineoplastics
Bevacizumab (Avastin)
Angiogenesis inhibitor
Blocks blood supply to the growing tumor
Used to treat metastatic colon cancer, rectal cancer in combination with 5-fluorouracil, non–small cell lung cancer, and malignant glioblastoma
Many adverse effects, including nephrotoxicity
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17. Audience Response System Question
Bevacizumab (Avastin) is an angiogenesis inhibitor. Which statement correctly describes the mechanism of action of an angiogenesis inhibitor?
It inhibits the formation of blood cells.
It inhibits the creation of new blood vessels in the tumor mass.
It interferes with the synthesis of DNA in the cancer tumor.
It causes cell death by inhibiting enzymes.
Correct answer: B
Rationale: Bevacizumab (Avastin) is the first approved angiogenesis inhibitor. Angiogenesis is the creation of new blood vessels that supply oxygen and other blood nutrients to growing tissues. In the case of malignant tumors, angiogenesis that occurs within the tumor mass promotes continued tumor growth. As a tumor enlarges, its central tissues gradually die off (necrosis). However, its outer portion continues to grow, often to fatal proportions, with blood supplied through angiogenesis. Thus, inhibiting this process offers a promising new mechanism for antineoplastic drug action.
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18. Miscellaneous Antineoplastics (Cont.)
Hydroxyurea (Hydrea, Droxia)
Action similar to antimetabolites
Used to treat squamous cell carcinoma and some leukemias
Many adverse effects such as edema, drowsiness, headache, rash, hyperuricemia, nausea, vomiting, dysuria, myelosuppression, nephrotoxicity, and pulmonary fibrosis
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19. Miscellaneous Antineoplastics (Cont.)
Imatinib (Gleevec)
Used to treat chronic myeloid leukemia (CML)
Targeted therapy, but it is NOT a monoclonal antibody
Works by inhibiting an enzyme that is active in the CML process
Use with other hepatic-metabolized drugs may cause severe interactions
Many adverse effects and drug interactions
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20. Miscellaneous Antineoplastics (Cont.)
Octreotide (Sandostatin)
Management of a cancer-related condition called carcinoid crisis
Treatment of the diarrhea caused by vasoactive intestinal peptide–secreting tumors (VIPomas)
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Hormonal Drugs
Used to treat a variety of neoplasms in men and women
Hormonal therapy used to:
Oppose effects of hormones
Block the body’s sex hormone receptors
Used most commonly as adjuvant and palliative therapy
But may be a drug of first choice for some cancers
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22. Hormonal Drugs for Female-Specific Neoplasms
Aromatase inhibitors
anastrozole, aminoglutethimide
Selective estrogen receptor modulators
tamoxifen, toremifene
Progestins
megestrol, medroxyprogesterone
Androgens
fluoxymesterone, testolactone
Estrogen receptor antagonist
fulvestrant
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23. Hormonal Drugs for Male-Specific Neoplasms
Antiandrogens
bicalutamide, flutamide, nilutamide
Antineoplastic hormone
estramustine
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Extravasation
Leaking of an antineoplastic drug into surrounding tissues during intravenous (IV) administration
Can result in permanent damage to nerves, tendons, muscles; loss of limbs
Skin grafting or amputation may be necessary
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Extravasation (Cont.)
Prevention is essential.
Continuous monitoring of the IV site is essential.
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Extravasation (Cont.)
If suspected, stop the infusion immediately and contact the prescriber but leave the IV catheter in place.
Aspirate any residual drug or blood from the catheter.
Consult guidelines or the pharmacist regarding antidotes, application of hot or cold packs or sterile occlusive dressings, and elevation and rest of the affected limb.
Thoroughly document the extravasation incident.
Consult facility protocol and guidelines.
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27. Audience Response System Question
When handling and administering vesicant drugs, the nurse will:
double flush the patient’s bodily secretions in the commode.
use sterile towels to clean up after chemotherapy spills.
mix chemotherapeutic drugs in the patient’s room.
teach the patient how to administer parenteral chemotherapeutic drugs.
Correct answer: A
Rationale: When providing care to patients receiving vesicant drugs as well as handling and administering these drugs, the nurse should double flush the patient’s bodily secretions in the commode and use special hampers for the disposal of all items that come in contact with the patient, including used personal protective equipment. If a spill occurs, the nurse should use special spill kits to clean up even the smallest chemotherapy spills. Nurses who are specially trained, current, and certified should administer chemotherapeutic agents.
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Nursing Implications
Assess baseline blood counts before administering antineoplastic drugs.
Follow specific administration guidelines for each antineoplastic drug.
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29. Nursing Implications (Cont.)
Alkylating drugs
Monitor for expected effects of bone marrow suppression.
Expect nausea, vomiting, diarrhea, and stomatitis.
Hydration is important to prevent nephrotoxicity.
Report ringing or roaring in the ears—possible ototoxicity.
Report tingling, numbness, or pain in the extremities—peripheral neuropathies may occur.
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30. Nursing Implications (Cont.)
Cytotoxic antibiotics
Expect bone marrow suppression, nausea, vomiting, diarrhea, and stomatitis.
Monitor pulmonary status because pulmonary fibrosis may occur.
Monitor for nephrotoxicity and liver toxicity.
Monitor cardiovascular status.
Daunorubicin may turn the urine a reddish color.
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31. Nursing Implications (Cont.)
In general:
Monitor closely for anaphylactic reactions.
Keep epinephrine, antihistamines, and antiinflammatory drugs on hand.
Monitor closely for complications associated with bone marrow suppression:
Anemia, thrombocytopenia, neutropenia
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32. Nursing Implications (Cont.)
Cytoprotective drugs may be used to reduce toxicities:
IV amifostine to reduce renal toxicity associated with cisplatin
IV or oral allopurinol to reduce hyperuricemia
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33. Nursing Implications (Cont.)
Monitor for oncologic emergencies:
Infections
Pulmonary toxicity
Allergic reactions
Stomatitis with severe ulcerations
Bleeding
Metabolic aberrations
Bowel irritability with diarrhea
Renal, liver, cardiac toxicity
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