Antineoplastic Drugs Cancer Overview and Cell Cycle–Specific Drugs

1. Antineoplastic Drugs Cancer Overview and Cell Cycle–Specific Drugs

2. Cancer Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs

3. 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. 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)

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

7. Paraneoplastic Syndromes Various group of symptoms May be the first sign of malignancy Cachexia (most common) Fatigue, fever, weight loss Others

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

10. 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

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. Cancer Drugs:Antineoplastic Medications (cont’d) Cell cycle–nonspecific drugs Cytotoxic during any phase of cellular replication

14. Cancer Drugs:Antineoplastic Medications (cont’d) Miscellaneous cell cycle–specific drugs Miscellaneous antineoplastics (cell-cycle specificity unclear) Hormonal agents Radioactive antineoplastics

15. 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. 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. 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. 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. 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. Antimetabolites (cont’d) Purine antagonism Interrupts metabolic pathways of purine nucleotides Results in interruption of DNA and RNA synthesis

21. Antimetabolites (cont’d) Pyrimidine antagonism Interrupts metabolic pathways of pyrimidine bases Results in interruption of DNA and RNA synthesis

22. 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. 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. 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. Antimetabolites: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Many other severe adverse effects

26. 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. Mitotic Inhibitors (cont’d) Vinca alkaloids (periwinkle) vinblastine, vincristine, vinorelbine Taxanes doxetaxel (European yew tree: needles) paclitaxel (western yew tree: bark)

28. 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. 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. Mitotic Inhibitors: Adverse Effects Hair loss, nausea and vomiting, myelosuppression Liver, kidney, lung toxicities Convulsions Extravasation Several specific antidotes can be used

31. 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. Topoisomerase-1 Inhibitors (Camptothecins) Derived from camptothecin, a substance taken from a Chinese shrub topotecan (Hycamtin) irinotecan (CPT-11, Camptosar)

33. Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Cell cycle–specific drugs Inhibit proper DNA function in the S phase Prevent DNA relegation

34. Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Indications Ovarian and colorectal cancer Small-cell lung cancer Other tumors

35. Topoisomerase-1 Inhibitors (Camptothecins) (cont’d) Adverse effects Bone marrow suppression (predictable, reversible, noncumulative, manageable) GI effects (nausea, vomiting, diarrhea)

36. 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. 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. 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. 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. 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. 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

42. Antineoplastic DrugsCell Cycle–Nonspecific and Miscellaneous Drugs

43. Cancer Drugs:Antineoplastic Medications Cell cycle–nonspecific (CCNS) drugs Alkylating drugs Cytotoxic antibiotics

44. Alkylating Drugs Classic alkylators (nitrogen mustards) Nitrosoureas Miscellaneous alkylators

45. 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. 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. 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. Alkylating Drugs: Examples cisplatin (Platinol) cyclophosphamide (Cytoxan) mechlorethamine (Mustine, nitrogen mustard) carmustine (BiCNU) Others

49. Cytotoxic Antibiotics Natural substances produced by the mold Streptomyces Synthetic substances also used Used to treat cancer; too toxic to treat infections

50. Cytotoxic Antibiotics (cont’d) All can produce BMS, except bleomycin Pulmonary toxicity: bleomycin Heart failure: daunorubicin Acute left ventricular failure (rare): doxorubicin