Antineoplastic Drugs Cancer Overview and Cell CycleSpecific Drugs

Antineoplastic Drugs Cancer Overview and Cell Cycle–Specific Drugs Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 2

Cancer (cont’d) Cancerous cells do not have: Ø Growth control mechanisms Ø Positive physiologic function Cancer cells either: Ø Grow and invade adjacent tissues, or Ø Break away from original tumor mass and travel by means of blood or lymphatic system to distant sites Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 3

Cancer (cont’d) Primary lesion Ø Original site of growth Metastasis Ø Uncontrolled cell growth Ø Secondary lesion, in a new and remote part of the body Neoplasm (“new tissue”) Ø Mass of new cells; tumor Tumor Ø Benign Ø Malignant (cancer) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 4

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Cancer: Tissues of Origin Carcinomas Sarcomas Lymphomas and leukemias Ø Also known as circulating tumors or hematologic malignancies Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 6

Paraneoplastic Syndromes Various group of symptoms May be the first sign of malignancy Ø Cachexia (most common) Ø Fatigue, fever, weight loss Ø Others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 7

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Etiology of Cancer Age- and sex-related differences Genetic factors Ethnic factors Oncogenic viruses Occupational and environmental carcinogens Radiation Immunologic factors Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 9

Chemotherapy Pharmacologic treatment of cancer Antineoplastic drugs Divided into two groups based on where in the cellular life cycle they work Ø Cell cycle–nonspecific (CCNS) Ø Cell cycle–specific (CCS) Some drugs have characteristics of both Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 10

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Cancer Drugs: Antineoplastic Medications Cell cycle–specific drugs Ø Drugs that are cytotoxic during a specific cell-cycle phase Ø Used to treat a variety of solid and/or circulating tumors • Antimetabolites • Mitotic inhibitors • Alkaloid topoisomerase II inhibitors • Topoisomerase I inhibitors • Antineoplastic enzymes Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 12

Cancer Drugs: Antineoplastic Medications (cont’d) Cell cycle–nonspecific drugs Ø Cytotoxic during any phase of cellular replication Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 13

Cancer Drugs: Antineoplastic Medications (cont’d) Miscellaneous cell cycle–specific drugs Miscellaneous antineoplastics (cellcycle specificity unclear) Hormonal agents Radioactive antineoplastics Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 14

Chemotherapy (cont’d) Drugs have a narrow therapeutic index A combination of drugs is usually more effective than single-drug therapy Drug resistance Nearly all drugs cause adverse effects Dose-limiting adverse effects Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 15

Chemotherapy (cont’d) Harmful to all rapidly growing cells Ø Harmful cancer cells Ø Healthy, normal human cells • Hair follicles • GI tract cells • Bone marrow cells Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 16

Chemotherapy Terms Dose-limiting adverse effects Ø GI tract and bone marrow Alopecia Emetic potential Myelosuppression Bone marrow suppression (BMS) Ø Bone marrow depression (BMD) Ø Nadir Extravasation Targeted drug therapy Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 17

Antimetabolites Folate (folic acid) antagonists Ø methotrexate (MTX), others Purine antagonists Ø fludarabine (F-AMP) Ø mercaptopurine (6 -MP) Ø thioguanine (6 -TG) Pyrimidine antagonists Ø fluorouracil (5 -FU) Ø cytarabine (ARA-C), others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 18

Antimetabolites (cont’d) Folic acid antagonism Ø Interferes with the use of folic acid Ø As a result, DNA is not produced, and the cell dies Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 19

Antimetabolites (cont’d) Purine antagonism Ø Interrupts metabolic pathways of purine nucleotides Ø Results in interruption of DNA and RNA synthesis Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 20

Antimetabolites (cont’d) Pyrimidine antagonism Ø Interrupts metabolic pathways of pyrimidine bases Ø Results in interruption of DNA and RNA synthesis Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 21

Antimetabolites: Indications Used in combination with other drugs to treat various types of cancer, such as solid tumors and some hematologic cancers Ø Acute and chronic lymphocytic leukemias Ø Leukemias (several types) Ø Colon, rectal, breast, stomach, lung, pancreatic cancers Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 22

Antimetabolites: Indications (cont’d) Oral and topical forms may be used for low-dose maintenance and palliative cancer therapy Often used in combination chemotherapy regimens Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 23

Antimetabolites: Methotrexate Immunosuppressive and antiinflammatory activity Also used for rheumatoid arthritis and psoriasis Leucovorin “rescue” (folic acid agonist) Ø Leucovorin given with folic acid antagonists to protect healthy cells and reduce bone marrow suppression Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 24

Antimetabolites: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Many other severe adverse effects Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 25

Mitotic Inhibitors Natural products obtained from the periwinkle plant Ø Vinca alkaloids Semisynthetic drugs obtained from the mandrake (mayapple) plant Drugs obtained from the yew tree Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 26

Mitotic Inhibitors (cont’d) Vinca alkaloids (periwinkle) Ø vinblastine, vincristine, vinorelbine Taxanes Ø doxetaxel (European yew tree: needles) Ø paclitaxel (western yew tree: bark) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 27

Mitotic Inhibitors (cont’d) Work in various phases of the cell cycle All work shortly before or during mitosis Result in slowing of cell division All classified as CCS drugs Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 28

Mitotic Inhibitors: Indications Often used in combination therapies Used to treat a variety of solid tumors and some hematologic malignancies Ø Testicular, small-cell lung, breast, ovarian, non–small-cell lung cancers Ø Kaposi’s sarcoma Ø Acute leukemia Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 29

Mitotic Inhibitors: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Liver, kidney, lung toxicities Convulsions Extravasation Ø Several specific antidotes can be used Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 30

Alkaloid Topoisomerase-II Inhibitors Derived from mandrake plants Used to treat small cell lung cancer and testicular cancer Not used as much now because of significant toxicities without therapeutic benefit Ø etoposide Ø teniposide Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 31

Topoisomerase-1 Inhibitors (Camptothecins) Derived from camptothecin, a substance taken from a Chinese shrub Ø topotecan (Hycamtin) Ø irinotecan (CPT-11, Camptosar) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 32

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Cell cycle–specific drugs Inhibit proper DNA function in the S phase Prevent DNA relegation Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 33

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Indications Ø Ovarian and colorectal cancer Ø Small-cell lung cancer Ø Other tumors Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 34

Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Adverse effects Ø Bone marrow suppression (predictable, reversible, noncumulative, manageable) Ø GI effects (nausea, vomiting, diarrhea) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 35

Antineoplastic Enzymes Synthesized using cultures of bacteria and recombinant DNA technology As a result, an enzyme is produced This enzyme is isolated and purified for clinical use Ø asparaginase (Elspar): used to treat acute lymphocytic leukemia Ø pegaspargase (Oncaspar) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 36

Nursing Implications (cont’d) Remember that all rapidly dividing cells (both normal and cancer cells) are affected Ø Mucous membranes Ø Hair follicles Ø Bone marrow component Monitor for effects on these tissues or complications Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 37

Nursing Implications (cont’d) Monitor for complications Ø GI mucous membranes: stomatitis, altered bowel function with high risk for poor appetite, nausea, vomiting, diarrhea, and inflammation and possible ulcerations of GI mucosa Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 38

Nursing Implications (cont’d) Monitor for complications Ø Hair follicles: loss of hair (alopecia) Ø Bone marrow components: dangerously low (life-threatening) blood cell counts Ø Possible stimulation of CTZ Monitor for adverse effects specific to the type of antineoplastic drug given. Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 39

Nursing Implications (cont’d) Implement measures to monitor for and prevent infection in patients with neutropenia or leukopenia Implement measures to monitor for and prevent bleeding in patients with thrombocytopenia and anemia Keep in mind that anemia may result in severe fatigue Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 40

Nursing Implications (cont’d) Monitor for stomatitis (oral inflammation and ulcerations), and implement measures to reduce the effects if it occurs Anticipate nausea and vomiting, and implement measures to reduce these effects Antiemetics often work better if given 30 to 60 minutes before chemotherapy is started Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 41

Antineoplastic Drugs Cell Cycle–Nonspecific and Miscellaneous Drugs Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc.

Cancer Drugs: Antineoplastic Medications Cell cycle–nonspecific (CCNS) drugs Ø Alkylating drugs Ø Cytotoxic antibiotics Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 43

Alkylating Drugs Classic alkylators (nitrogen mustards) Nitrosoureas Miscellaneous alkylators Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 44

Alkylating Drugs (cont’d) CCNS antineoplastics Effective at any stage in the growth cycle of cancer cells Prevent cancer cells from reproducing with the process of alkylation Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 45

Alkylating Drugs: Indications Used in combination with other drugs to treat various types of cancer, such as: Ø Recurrent ovarian cancer Ø Brain tumors Ø Lymphomas Ø Leukemias Ø Various forms of cancer (breast, ovarian, bladder) Ø Others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 46

Alkylating Drugs: Adverse Effects Dose-limiting adverse effects Ø Nausea and vomiting, myelosuppression Alopecia Nephrotoxicity, peripheral neuropathy, ototoxicity Ø Hydration can prevent nephrotoxicity Extravasation causes tissue damage and necrosis Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 47

Alkylating Drugs: Examples cisplatin (Platinol) cyclophosphamide (Cytoxan) mechlorethamine (Mustine, nitrogen mustard) carmustine (Bi. CNU) Others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 48

Cytotoxic Antibiotics Natural substances produced by the mold Streptomyces Synthetic substances also used Used to treat cancer; too toxic to treat infections Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 49

Cytotoxic Antibiotics (cont’d) All can produce BMS, except bleomycin Pulmonary toxicity: bleomycin Heart failure: daunorubicin Acute left ventricular failure (rare): doxorubicin Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 50

Cytotoxic Antibiotics (cont’d) Anthracycline antibiotics Ø daunorubicin, others doxorubicin, idarubicin, Anthracenedione antibiotic Ø mitoxantrone Other cytotoxic antibiotics Ø bleomycin, dactinomycin, mitomycin Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 51

Cytotoxic Antibiotics (cont’d) CCNS drugs are active in all phases of the cell cycle Act by blockade of DNA synthesis Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 52

Cytotoxic Antibiotics: Indications Used in combination chemotherapy regimens Used to treat a variety of solid tumors and some hematologic malignancies Ø Leukemia, ovarian, breast, bone, others Ø Squamous cell carcinomas Ø AIDS-related Kaposi’s sarcoma (when intolerant to other treatments) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 53

Cytotoxic Antibiotics: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Pulmonary fibrosis and pneumonitis (bleomycin) Liver, kidney, and cardiovascular toxicities Many others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 54

Cytotoxic Antibiotics: Adverse Effects (cont’d) Cardiomyopathy is associated with large amounts of doxorubicin Ø Dexrazoxane can be used as a cytoprotective drug Ø Monitor cardiac ejection fractions Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 55

Miscellaneous Antineoplastics bevacizumab (Avastin) hydroxyurea (Hydrea) imatinib (Gleevec) mitotane (Lysodren) Radiopharmaceuticals Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 56

Miscellaneous Antineoplastics (cont’d) bevacizumab (Avastin) Ø Angiogenesis inhibitor Ø Blocks blood supply to the growing tumor Ø Many adverse effects, including nephrotoxicity Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 57

Miscellaneous Antineoplastics (cont’d) hydroxyurea (Hydrea) Ø Action similar to antimetabolites Ø Used to treat squamous cell carcinoma and some leukemias Ø Oral form only Ø Many adverse effects Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 58

Miscellaneous Antineoplastics (cont’d) imatinib (Gleevec) Ø Used to treat chronic myeloid leukemia (CML) Ø Targeted therapy, but it is NOT a monoclonal antibody Ø Works by inhibiting an enzyme that is active in the CML process Ø Use with other hepatic-metabolized drugs may cause severe interactions Ø Many adverse effects and drug interactions Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 59

Miscellaneous Antineoplastics (cont’d) mitotane (Lysodren) Ø Adrenal cytotoxic drug Ø Used specifically for adrenal corticoid carcinoma Ø Oral form only Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 60

Hormonal Drugs Used to treat a variety of neoplasms in men and women Hormonal therapy used to Ø Oppose effects of hormones Ø Block the body’s sex hormone receptors Used most commonly as adjuvant and palliative therapy Ø But may be a drug of first choice for some cancers Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 61

Hormonal Drugs for Female. Specific Neoplasms Aromatase inhibitors Ø anastrozole, Selective estrogen receptor modulators Ø tamoxifen, toremifene Progestins Ø megestrol aminoglutethimide (Megace), medroxyprogesterone Androgens Ø fluoxymesterone, testolactone Estrogen receptor antagonist Ø fulvestrant Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 62

Hormonal Drugs for Male-Specific Neoplasms Antiandrogens Ø bicalutamide, flutamide, nilutamide Antineoplastic hormone Ø estramustine Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 63

Radiopharmaceuticals and Antineoplastics Radiopharmaceuticals Ø Used to treat a variety of cancers, or symptoms caused by cancers Ø Administered by nuclear medicine specialists • porfimer sodium • chromic phosphate P 32 • samarium SM 153 lexidronam • sodium iodide I 131 • sodium phosphate P 32 • strontium Sr 89 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 64

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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 65

Extravasation (cont’d) Prevention is essential Continuous monitoring of the IV site is essential Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 66

Extravasation (cont’d) If suspected, stop the IV infusion immediately but do not remove the IV tube If possible, aspirate remaining drug or blood from the tube Follow instructions for giving the appropriate antidote through the existing IV tube, then remove the catheter Some antidotes are not given through the IV catheter Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 67

Extravasation (cont’d) Cover area with sterile, occlusive dressing if ordered Apply warm or cold compresses, depending on the extravasated drug Rest and elevate the affected limb PREVENTION is the best approach! Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 68

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Handling Antineoplastic Drugs Those preparing and administering these drugs may be exposed to negative consequences Most facilities have these drugs mixed under special environments in the pharmacy Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 71

Handling Antineoplastic Drugs (cont’d) During care of a patient receiving these drugs, special precautions may be implemented, depending on facility policies Ø Double flushing of bodily fluids in the commode Ø Special hampers for disposal of all objects that contact the patient’s bodily fluids Ø Personal protective equipment Ø Special concerns if chemotherapy liquid spills Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 72

Nursing Implications (cont’d) Alkylating drugs Ø Monitor for expected effects of bone marrow suppression Ø Expect nausea, vomiting, diarrhea, stomatitis Ø Hydration is important to prevent nephrotoxicity Ø Report ringing/roaring in the ears—possible ototoxicity Ø Report tingling, numbness, or pain in extremities— peripheral neuropathies may occur Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 73

Nursing Implications (cont’d) Cytotoxic antibiotics Ø Expect bone marrow suppression, nausea, vomiting, diarrhea, stomatitis Ø Monitor pulmonary status Ø Monitor for nephrotoxicity, liver toxicity Ø Monitor cardiovascular status Ø Daunorubicin may turn the urine a reddish color Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 74

Nursing Implications (cont’d) In general: Ø Monitor closely for anaphylactic reactions Ø Keep epinephrine, antihistamines, and antiinflammatory drugs on hand Ø Monitor closely for complications associated with bone marrow suppression • Anemia, thrombocytopenia, neutropenia Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 75

Nursing Implications (cont’d) Cytoprotective drugs may be used to reduce toxicities Ø IV amifostine to reduce renal toxicity associated with cisplatin Ø IV or PO allopurinol to reduce hyperuricemia Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 76

Nursing Implications (cont’d) Monitor for oncologic emergencies Ø Infections Ø Pulmonary toxicity Ø Allergic reactions Ø Stomatitis with severe ulcerations Ø Bleeding Ø Metabolic aberrations Ø Bowel irritability with diarrhea Ø Renal, liver, cardiac toxicity Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 77