Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Pharmacology in Nursing Antineoplastic Drugs Part 1: Cancer Overview and Cell Cycle– Specific Drugs

Mosby items and derived items © 2007, 2005, 2002 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 © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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)

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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. 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 © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cell Growth Cycle  G 0 –resting phase  G 1 –postmitotic phase  S –DNA synthesis phase  M –mitosis phase (cell reproduction)

Mosby items and derived items © 2007, 2005, 2002 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

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Cancer Drugs: Antineoplastic Medications  Cell cycle–nonspecific drugs  Cytotoxic during a specific cell-cycle stage  More effective against large, slowly growing tumors  Alkylating drugs  Cytotoxic antibiotics

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cancer Drugs Antineoplastic Medications (cont’d)  Cell cycle–specific drugs  Drugs that are cytotoxic during a specific cell-cycle phase  More effective against rapidly growing tumors  Antimetabolites: folate, purine, and pyrimidine analogs  Natural products: enzymes, vinca alkaloids, others

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chemotherapy (cont’d)  Drugs have a narrow therapeutic index  Combination of drugs is usually more effective than single-drug therapy  Drug resistance  Nearly all drugs cause adverse effects  Dose-limiting adverse effects

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Chemotherapy (cont'd)  Harmful to all rapidly growing cells  Harmful cancer cells  Healthy, normal human cells Hair follicles Hair follicles GI tract cells GI tract cells Bone marrow cells Bone marrow cells

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chemotherapy Terms  Alopecia  Emetic potential  Myelosuppression  Bone marrow suppression (BMS)  Bone marrow depression (BMD)  Nadir (low point)  Extravasation

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antimetabolites  Folic acid antagonist  methotrexate (MTX), others  Purine antagonists  fludarabine (F-AMP)  mercaptopurine (6-MP)  allopurionol, others  Pyrimidine antagonists  fluorouracil (5-FU)  cytarabine (ARA-C), others

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antimetabolites (cont’d)  Purine antagonism  Interrupts metabolic pathways of purine nucleotides  Results in the interruption of the synthesis of DNA and RNA

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antimetabolites (cont’d)  Pyrimidine antagonism  Interrupts metabolic pathways of pyrimidine bases  Results in interruption of the synthesis of DNA and RNA

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antimetabolites: Adverse Effects  Hair loss, nausea and vomiting, myelosuppression  Many other severe adverse effects  Leucovorin rescue may be done to reduce severe bone marrow suppression

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Mitotic Inhibitors (cont’d)  Vinca alkaloids (periwinkle)  vinblastine, vincristine, vinorelbine  Epipodophyllotoxin derivatives (mandrake plant)  etoposide, teniposide  Taxanes  doxetaxel (European yew tree: needles)  paclitaxel (western yew tree: bark)

Mosby items and derived items © 2007, 2005, 2002 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  Results in slowing of cell division  All classified as CCS drugs

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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)

Mosby items and derived items © 2007, 2005, 2002 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 religation

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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)  Irinotecan causes cholinergic diarrhea (delayed, occurring 2 to 10 days after dosage)

Mosby items and derived items © 2007, 2005, 2002 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)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Assess baseline blood counts before giving any antineoplastic drugs  Follow specific administration guidelines for each antineoplastic drug

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 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 (chemoreceptor trigger zone)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) Monitor for adverse effects specific to the type of antineoplastic drug given

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) Implement measures to monitor for and prevent bleeding in patients with thrombocytopenia and anemia

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) Keep in mind that anemia may result in severe fatigue

Mosby items and derived items © 2007, 2005, 2002 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

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) 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 30 to 60 minutes before chemotherapy is started

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d) Women of childbearing age will need to use a nondrug form of contraception during therapy

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  In addition to physical measures, keep in mind the need for emotional support during this time for both the patient and family  Monitor for therapeutic responses to antineoplastic therapies and the many possible adverse effects