Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Chapter 45 Antineoplastic Drugs Part 1: Cancer Overview and Cell Cycle–Specific Drugs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Cancer Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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

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

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

Cancer: Tissues of Origin Carcinomas Sarcomas Lymphomas and leukemias Also known as circulating tumors or hematologic malignancies Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Paraneoplastic Syndromes Various group of symptoms that cannot be directly attributed to the spread of a cancerous tumor May be the first sign of malignancy Cachexia (most common) Fatigue, fever, weight loss Others Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Etiology of Cancer Age- and sex-related differences Genetic factors Ethnic factors Oncogenic viruses Occupational and environmental carcinogens Radiation Immunologic factors Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Cell Growth Cycle G0: resting phase G1: first gap phase S: synthesis phase G2: second gap phase M: mitosis phase (cell reproduction) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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

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

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

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

Cancer Drugs: Antineoplastic Medications (cont’d) Cell cycle–nonspecific drugs Cytotoxic during any cell-cycle stage Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Cancer Drugs: Antineoplastic Medications (cont’d) Miscellaneous cell cycle–specific drugs Miscellaneous antineoplastics (cell-cycle specificity unclear) Hormonal agents Radioactive antineoplastics Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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

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

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Antimetabolites Folate (folic acid) antagonists methotrexate (MTX), pemetrexed, palatrexate Purine antagonists fludarabine (F-AMP),mercaptopurine (6-MP), thioguanine (6-TG), cladribine, pentostatin Pyrimidine antagonists fluorouracil (5-FU), cytarabine (ara-C), capecitabine, floxuridine (FUDR), gemcitabine Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antimetabolites (cont’d) Purine antagonism Interrupts metabolic pathways of purine nucleotides Results in interruption of DNA and RNA synthesis Tumor lysis syndrome Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antimetabolites (cont’d) Pyrimidine antagonism Interrupts metabolic pathways of pyrimidine bases Results in interruption of DNA and RNA synthesis Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Methotrexate is also used to treat severe cases of psoriasis and rheumatoid arthritis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antimetabolites: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Neurologic, cardiovascular, pulmonary, hepatobiliary, GI, genitourinary, dermatologic, ocular, otic, and metabolic toxicity Tumor lysis syndrome Palmar-plantar dysesthesia (also called hand-foot syndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question Which condition does the nurse anticipate when assessing a patient with tumor lysis syndrome? Hyperuricemia Hypophosphatemia Hypokalemia Hypercalcemia Correct answer: A Rationale: Manifestations of tumor lysis syndrome include hyperphosphatemia, hyperkalemia, and hypocalcemia. These electrolyte abnormalities are often treated with diuretics such as mannitol, IV calcium supplementation, oral or rectal potassium exchange resin, and oral aluminum hydroxide. Hyperuricemia can lead to nephropathy, and hemodialysis may be required in severe cases of tumor lysis syndrome. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Classroom Response Question A patient who is receiving high-dose chemotherapy with methotrexate is also receiving leucovorin. The purpose of the leucovorin is to: produce an additive effect with the methotrexate by increasing its potency against the cancer cells. reduce the incidence of cardiomyopathy caused by the methotrexate. add its antiinflammatory effects to the treatment regimen. reduce the bone marrow suppression caused by the methotrexate. Correct answer: D Rationale: Leucovorin “rescue” is prescribed to reduce the bone marrow suppression that is associated with high-dose methotrexate therapy. 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. 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Mitotic Inhibitors (cont’d) Vinca alkaloids (periwinkle) vinblastine, vincristine, vinorelbine Taxanes docetaxel (European yew tree: needles) paclitaxel (western yew tree: bark) cabazitaxel eribulin Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Mitotic Inhibitors: Mechanism of Action Can work in various phases of the cell cycle (late S phase, throughout G2 phase, and M phase) All work shortly before or during mitosis and thus retard cell division Each different subclass inhibits mitosis in a unique way Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question The nurse identifies which of the following as the most significant neurotoxin of the cytotoxic drug class? paclitaxel (Taxol) docetaxel (Taxotere) vincristine (Vincasar PFS) etoposide (Toposar) Correct answer: C Rationale: Vincristine is the most significant neurotoxin of the cytotoxic drug class, but it continues to be used in part because of its relative lack of bone marrow suppression. Special care must be taken not to inadvertently give vincristine via the intrathecal route. Several deaths have been reported due to this error. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Topoisomerase 1 Inhibitors (Camptothecins) Derived from camptothecin, a substance taken from a Chinese shrub topotecan (Hycamtin) irinotecan (CPT-11, Camptosar) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Topoisomerase 1 Inhibitors (Camptothecins) (cont’d) Cell cycle–specific drugs Inhibit proper DNA function in the S phase Prevent DNA relegation Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Topoisomerase 1 Inhibitors (Camptothecins) (cont’d) Indications Ovarian and colorectal cancer Small cell lung cancer Other tumors Copyright © 2014 by Mosby, an imprint 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) Copyright © 2014 by Mosby, an imprint 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) Copyright © 2014 by Mosby, 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.

Classroom Response Question A pregnant woman has been diagnosed with cancer and is meeting with her oncologist to plan treatment. Which statement about chemotherapy and pregnancy is true? She will have to wait until the baby is born before starting chemotherapy. The greatest risk of fetal harm from chemotherapy is during the third trimester. Chemotherapy treatment during the second or third trimester poses less risk to the fetus. Chemotherapy is unsafe during pregnancy, but radiation therapy is safe in low doses. Correct answer: C Rationale: Both radiation and chemotherapy treatments can cause significant permanent fetal harm or death. The greatest risk is during the first trimester. Chemotherapy treatment during the second or third trimester is more likely to improve maternal outcome without significant fetal risk. However, radiation treatment poses great risk to the fetus throughout pregnancy and should be reserved for the postpartum period if possible. Prepubertal patients are more resilient, however, and can have normal puberty and fertility. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint 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 Monitor for adverse effects specific to the type of antineoplastic drug given Copyright © 2014 by Mosby, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question The nurse is caring for a patient who received chemotherapy 24 hours ago. The patient’s white blood cell count is 4,400 mcL. Which symptom, if experienced by the patient, should the nurse report to the prescriber immediately? Fatigue Diarrhea Fever Nausea and vomiting Correct answer: C Rationale: Fever is the principal early sign of infection, especially in those with a low white blood cell count. The presence of a fever is of utmost concern and should be reported immediately. Normal white blood cell count is 4,500-10,000 mcL. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Nursing Implications (cont’d) Women of childbearing age will need to use a nondrug form of contraception during therapy 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Classroom Response Question When working with a patient who is neutropenic, the nurse identifies which as the most effective measure to prevent the patient from developing an infection? Administer prophylactic antibiotics Stop administration of the chemotherapeutic drug Perform hand hygiene Vaccinate the patient to prevent bacterial infection Correct answer: C Rationale: Risk of infection from leukopenia or neutropenia and/or immunosuppression is one of the more significant adverse effects that requires close attention. Following Standard Precautions and using good handwashing technique are most important in preventing transmission of infection in the hospital and home settings. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.