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

2 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

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

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

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

6 Cancer: Tissues of Origin   Carcinomas   Sarcomas   Lymphomas and leukemias   Also known as circulating tumors or hematologic malignancies

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

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

9 Etiology of Cancer   Age- and sex-related differences   Genetic factors   Ethnic factors   Oncogenic viruses   Occupational and environmental carcinogens   Radiation   Immunologic factors

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

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

12 Cancer Drugs: Antineoplastic Medications   Cell cycle–specific drugs   Drugs that are cytotoxic during a specific cell-cycle phase   Used to treat a variety of solid and/or circulating tumors Antimetabolites Mitotic inhibitors Alkaloid topoisomerase II inhibitors Topoisomerase I inhibitors Antineoplastic enzymes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

31 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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   etoposide   teniposide

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

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

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

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

36 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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   asparaginase (Elspar): used to treat acute lymphocytic leukemia   pegaspargase (Oncaspar)

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

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

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

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

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

43 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   Alkylating drugs   Cytotoxic antibiotics

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

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

46 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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   Various forms of cancer (breast, ovarian, bladder)   Others

47 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

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

49 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

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

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

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

53 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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)

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

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

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

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

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

59 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

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

61 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

62 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

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

64 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Radiopharmaceuticals and Antineoplastics   Radiopharmaceuticals   Used to treat a variety of cancers, or symptoms caused by cancers   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

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

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

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

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

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

70

71 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

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

73 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

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

75 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

76 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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

77 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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