Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Chapter 46 Antineoplastic Drugs Part 2: Cell Cycle – Nonspecific Drugs and Miscellaneous Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cancer Drugs: Antineoplastic Medications Cell cycle–nonspecific (CCNS) antineoplastic drugs Alkylating drugs Cytotoxic antibiotics Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Alkylating Drugs Classic alkylators (nitrogen mustards) Nitrosoureas Miscellaneous alkylators Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Organization of DNA and Site of Action of Alkylating Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Alkylating Drugs: Examples cisplatin (Platinol) cyclophosphamide (Cytoxan) mechlorethamine (Mustine, nitrogen mustard) carmustine (BiCNU) Others Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cytotoxic Antibiotics Natural substances produced by the mold Streptomyces Synthetic substances also used Used to treat cancer; too toxic to treat infections Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cytotoxic Antibiotics (cont’d) Anthracycline antibiotics daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin Other cytotoxic antibiotics bleomycin, dactinomycin, mitomycin, mitoxantrone, plicamycin Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cytotoxic Antibiotics: Adverse Effects (cont’d) Pulmonary fibrosis and pneumonitis (bleomycin) Liver, kidney, and cardiovascular toxicities Many others Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cytotoxic Antibiotics: Adverse Effects (cont’d) 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response 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. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response 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. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Miscellaneous Antineoplastics (cont’d) hydroxyurea (Hydrea, Droxia) Action similar to antimetabolites Used to treat squamous cell carcinoma and some leukemias Many adverse effects (e.g., edema, drowsiness, headache, rash, hyperuricemia, nausea, vomiting, dysuria, myelosuppression, nephrotoxicity, pulmonary fibrosis) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Miscellaneous Antineoplastics (cont’d) 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Miscellaneous Antineoplastics (cont’d) mitotane (Lysodren) Adrenal cytotoxic drug Used specifically for inoperable adrenal corticoid carcinoma Oral form only Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Hormonal Drugs for Female-Specific Neoplasms Aromatase inhibitors anastrozole, aminoglutethimide Selective estrogen receptor modulators tamoxifen, toremifene Progestins megestrol (Megace), medroxyprogesterone Androgens fluoxymesterone, testolactone Estrogen receptor antagonist fulvestrant Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Hormonal Drugs for Male-Specific Neoplasms Antiandrogens bicalutamide, flutamide, nilutamide Gonadotropin-releasing hormone antagonists leuprolide, goserelin Antineoplastic hormone estramustine Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Radiopharmaceuticals and Antineoplastics Porfimer sodium Used to treat esophageal and bronchial tumors in combination with laser light therapy Radiopharmaceuticals Used to treat a variety of cancers, or symptoms caused by cancers Administered by nuclear medicine specialists samarium SM 153 lexidronam sodium iodide I 131 sodium phosphate P 32 Others Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Extravasation Leaking of an antineoplastic drug into surrounding tissues during IV administration Can result in permanent damage to nerves, tendons, muscles; loss of limbs Skin grafting or amputation may be necessary Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Extravasation (cont’d) Prevention is essential Continuous monitoring of the IV site is essential Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Extravasation (cont’d) If suspected, stop the infusion immediately and contact the prescriber, but leave the intravenous catheter in place Aspirate any residual drug and/or blood from the catheter Consult guidelines or the pharmacist regarding antidotes, application of hot or cold packs and/or sterile occlusive dressings, and elevation and rest of the affected limb Thoroughly document the extravasation incident Consult facility protocol and guidelines Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response 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 should occur, 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. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Nursing Implications Assess baseline blood counts before administering antineoplastic drugs Follow specific administration guidelines for each antineoplastic drug Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Alkylating drugs Monitor for expected effects of bone marrow suppression Expect nausea, vomiting, diarrhea, stomatitis Hydration is important to prevent nephrotoxicity Report ringing/roaring in the ears—possible ototoxicity Report tingling, numbness, or pain in extremities— peripheral neuropathies may occur Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Cytotoxic antibiotics Expect bone marrow suppression, nausea, vomiting, diarrhea, stomatitis Monitor pulmonary status, since pulmonary fibrosis may occur Monitor for nephrotoxicity, liver toxicity Monitor cardiovascular status Daunorubicin may turn the urine a reddish color Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Cytoprotective drugs may be used to reduce toxicities IV amifostine to reduce renal toxicity associated with cisplatin IV or PO allopurinol to reduce hyperuricemia Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Monitor for oncologic emergencies Infections Pulmonary toxicity Allergic reactions Stomatitis with severe ulcerations Bleeding Metabolic aberrations Bowel irritability with diarrhea Renal, liver, cardiac toxicity Copyright © 2014 by Mosby, an imprint of Elsevier Inc.