1. 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.

2. 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.

3. 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.

4. 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.

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

6. 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.

7. 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.

8. 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.

9. 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.

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

11. 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.

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

13. 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.

14. 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.

15. 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.

16. 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.

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

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.