1. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 49 Biologic Response–Modifying Drugs

2. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Immunomodulators (IMs)  Include drugs from several classes  Immunosuppressants  Immunizing drugs  Biologic response modifiers (BRMs)  Miscellaneous IMs

3. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Biologic Response Modifiers (BRMs)  Medications that therapeutically alter a patient’s immune response to malignant tumor cells  Drugs that modify the body’s own immune response so that it can destroy various viruses and cancerous cells

4. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Biologic Response Modifiers (BRMs) (cont’d)  Fourth part of cancer therapy, in addition to:  Surgery  Chemotherapy  Radiation  Also used for other diseases  Autoimmune  Inflammatory  Infectious

5. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. BRMs: Subclasses  Hematopoietic drugs  Interferons (IFNs)  Monoclonal antibodies  Interleukin receptor agonists and antagonists  Miscellaneous drugs

6. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. BRMs: Three Mechanisms of Action  Enhancing or restoring the host’s immune system defenses against the tumor  Using drugs that are directly toxic to tumor cells, causing them to rupture (lyse)  Modifying the tumor’s biology  Tumor cells cannot survive and reproduce

7. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. The Immune System  Two components of the immune system work together to recognize and destroy foreign particles and cells in the blood or other body tissues  Humoral immunity Mediated by B-cell functions (antibodies) Mediated by B-cell functions (antibodies)  Cell-mediated immunity (CMI) Mediated by T-cell functions Mediated by T-cell functions

8. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. The Immune System (cont’d)  Tumor antigens (chemical or tumor “markers”) label tumor cells as abnormal cells  Antibodies attack tumor cells  B-lymphocytes (B-cells) from the humoral immune system  T-lymphocytes (T-cells) from the cell-mediated immune system

9. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Humoral Immune System  B-lymphocytes (B-cells)  Originate from bone marrow  When a foreign substance (antigen) is present, these turn into plasma cells, which in turn produce antibodies  Antibody-antigen complex  Memory cells

10. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Humoral Immune System (cont’d)  Antibodies also known as immunoglobulins (Ig)  Monoclonal antibodies  Five major types of naturally occurring immunoglobulins  IgA, IgD, IgE, IgG, IgM

11. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

12. Cell-Mediated Immune System  T-lymphocytes (T-cells)  Originate from bone marrow but mature in the thymus gland  Three types, with different functions  Cytotoxic T-cells  T-helper cells  T-suppressor cells

13. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cell-Mediated Immune System (cont’d)  Cytotoxic T-cells directly kill their targets by causing cell lysis or rupture  T-helper cells direct the actions of many other components of the immune system  T-suppressor cells serve to limit or control the immune response

14. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cell-Mediated Immune System (cont’d)  A healthy immune system has about twice as many T-helper cells as T-suppressor cells at any one time  Overactive T-suppressor cells may be responsible for clinically significant cancer cases by permitting tumor growth beyond immune system control

15. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cell-Mediated Immune System (cont’d)  Other cells of the CMI help to destroy cancer cells  Macrophages (derived from monocytes)  Natural killer (NK) cells  Polymorphonuclear (PMN) leukocytes (neutrophils)

16. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

17. Therapeutic Effects of BRMs  Regulation or enhancement of the immune response  Cytotoxic or cytostatic activity against cancer cells  Inhibition of metastases, prevention of cell division, or inhibition of cell maturation

18. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs  HDs promote the synthesis of various types of major blood components by promoting the growth, or differentiation, and function of their precursor cells in the bone marrow  Produced by rDNA technology

19. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  HDs are used to:  Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia  Enable higher doses of chemotherapy to be given  Other uses

20. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  Colony-stimulating factors (CSFs)  filgrastim (Neupogen)  pegfilgrastim (Neulasta)  sargramostin (Leukine)  epoetin alfa (Epogen, Procrit)  darbepoetin alfa (Aranesp)  oprelvekin (Neumega)

21. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  epoetin alfa  Synthetic derivative of the hormone erythropoietin  Promotes the synthesis of RBCs by stimulating RBC precursors

22. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  darbepoetin alfa  Longer acting form of epoetin alfa  Also used to stimulate RBC production

23. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  filgrastim  Granulocyte colony-stimulating factor (G-CSF)  Stimulates precursor cells for the type of WBCs known as granulocytes  pegfilgrastim  Longer acting form of filgrastim

24. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  sargramostim  Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells, known as monocytes  Granulocyte-macrophage colony-stimulating factor (GM-CSF)

25. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs (cont’d)  oprelvekin  Also classified as an interleukin (IL-11)  Stimulates the bone marrow cells, megakaryocytes, that eventually become platelets

26. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs: Indications Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy

27. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs: Indications (cont’d)  Decrease the duration of low neutrophil counts, thus reducing the incidence and duration of infections  Enhance the functioning of mature cells of the immune system, resulting in greater ability to kill cancer cells as well as viral- and fungal- infected cells

28. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs: Indications (cont’d)  Also enhance RBC and platelet counts in patients with bone marrow suppression due to chemotherapy  Allow for higher doses of chemotherapy, resulting in the destruction of a greater number of cancer cells

29. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs: Adverse Effects  Usually mild  Fever  Muscle aches  Bone pain  Flushing

30. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hematopoietic Drugs: Interactions  Filgrastim and sargramostim should not be given within 24 hours of myelosuppressive antineoplastic therapy  These two types of drugs will directly antagonize each other

31. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (IFNs)  Proteins with three basic properties  Antiviral  Antitumor  Immunomodulating  Used to treat certain viral infections and cancer

32. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (cont’d)  Manufactured from Escherichia coli bacteria with rDNA technology  Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens

33. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (cont’d)  Recombinantly made IFNs are identical to the IFNs that are present within the human body and have the same properties  IFNs protect human cells from viruses and prevent cancer cells from dividing and replicating

34. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons: Effects on Immune System  Restore the immune system’s function if it is impaired  Augment the immune system’s ability to function as the body’s defense  Inhibit the immune system from working  Helpful in autoimmune disorders

35. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons: Indications  Viral infections  Genital warts, hepatitis  Cancer  Chronic myelogenous leukemia, follicular lymphoma, hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma  Autoimmune disorders  Multiple sclerosis, others

36. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons: Adverse Effects  Flulike effects  Fever, chills, headache, malaise, myalgia, fatigue  *Dose-limiting adverse effect is fatigue*  Other adverse effects  Anorexia, dizziness, nausea, vomiting, diarrhea

37. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (cont’d)  Three major classes of IFNs  Alfa  Beta  Gamma

38. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (cont’d)  Interferon alfa products: “leukocyte interferons”—produced from human leukocytes  Interferon alfa-2a, Interferon alfa-2b  Interferon alfa-n3, Interferon alfacon-1  Peginterferon alfa-2a  Peginterferon alfa-2b

39. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interferons (cont’d)  Interferon beta products  IFN beta-1a  IFN beta-1b  Interferon gamma products  Interferon gamma-1b

40. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monoclonal Antibodies (MABs)  Used to target specific cancer cells  Minimal effect on healthy cells  Fewer adverse effects than traditional antineoplastic medications

41. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monoclonal Antibodies (MABs) (cont’d)  MABs used for cancer treatment:  alemtuzumab (Campath)  gemtuzumab ozogamicin (Mylotarg)  ibritumomab tiuxetan (Zevalin)  rituximab (Rituxan)  trastuzumab (Herceptin)

42. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Monoclonal Antibodies (MABs) (cont’d)  Mechanisms of action and adverse effects vary with each drug  Used for specific types of cancer and in organ transplantation  Extremely specific drugs that target certain tumor cells and bypass normal cells

43. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interleukins and Related Drugs  Interleukin receptor agonists  aldesleukin (IL-2, Proleukin)  oprelvekin (IL-11, Neumega)*  denileukin diftitox (Ontak)  IL-1 receptor antagonist  anakinra (Kineret) *Also classified as an HD

44. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interleukins Beneficial antitumor action

45. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interleukins (cont’d)  Aldesleukin acts indirectly to stimulate or restore immune response  Aids in causing T-cells to multiply, including lymphokine- activated killer (LAK) cells  LAK cells recognize and destroy only cancer cells, and ignore normal cells  Used for metastatic renal cell carcinoma  Under study for use in other types of cancer

46. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Capillary Leak Syndrome  Severe toxicity of aldesleukin therapy  Capillaries lose ability to retain vital colloids in the blood; these substances are “leaked” into the surrounding tissues  Result: massive fluid retention Respiratory distress, heart failure, MI, dysrhythmias Respiratory distress, heart failure, MI, dysrhythmias  Reversible after interleukin therapy discontinued

47. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interleukins (cont’d)  denileukin diftitox  IL-2 receptor antagonist (IL-2Ra)  Binds to cell-surface IL-2 receptors on normal as well as certain malignant cells  Causes cell death

48. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Interleukins (cont’d)  anakinra (Kineret)  IL-1 receptor antagonist  Used to control symptoms of rheumatoid arthritis

49. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Assess for allergies, including allergies to egg proteins, IgG, or neomycin  Assess for conditions that may be contraindications  Assess baseline blood counts, cardiac, renal, and liver studies  Assess for presence of infection

50. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Follow specific guidelines for preparation and administration of drugs  Monitor the patient’s response during therapy

51. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Teach patients to report signs of infection immediately  Sore throat  Diarrhea  Vomiting  Fever over 100° F

52. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Monitor for therapeutic responses  Decrease in growth of lesion or mass  Improved blood counts  Absence of infection, anemia, and hemorrhage  Monitor for adverse effects