1. Biologic Response–Modifying and Antirheumatic Drugs
Winter 2013

2. Immunomodulators (IMs)
Include drugs from several classes
Immunosuppressants
Immunizing drugs
Biologic response modifiers (BRMs)
Hematopoietic drugs
Immunomodulating drugs
Winter 2013

3. Immunomodulating Drugs
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
Winter 2013

4. Biologic Response Modifiers (BRMs)
Fourth part of cancer therapy, in addition to:
Surgery
Chemotherapy
Radiation
Also used for other diseases
Autoimmune
Inflammatory
Infectious
Winter 2013

5. BRMs: Subclasses Hematopoietic drugs Interferons (IFNs)
Monoclonal antibodies
Interleukin receptor agonists and antagonists
Disease-modifying antirheumatic drugs
Miscellaneous drugs
Winter 2013

6. 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
Winter 2013

7. 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
Winter 2013

8. 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
Winter 2013

9. Hematopoietic Drugs (cont’d)
Erythropoietic drugs
epoetin Alpha (Epogen, Procrit)
darbepoetin Alpha (Aranesp)
Colony-stimulating factors (CSFs)
filgrastim (Neupogen)
pegfilgrastim (Neulasta)
sargramostin (Leukine)
Platelet-promoting drugs
oprelvekin (Neumega)
Winter 2013

10. Hematopoietic Drugs (cont’d)
epoetin Alpha (Epogen, Procrit)
Synthetic derivative of the hormone erythropoietin
Promotes the synthesis of RBCs by stimulating RBC precursors
Winter 2013

11. Hematopoietic Drugs (cont’d)
darbepoetin Alpha (Aranesp)
Longer-acting form of epoetin Alpha
Also used to stimulate RBC production
Winter 2013

12. Hematopoietic Drugs (cont’d)
filgrastim (Neupogen)
Granulocyte colony-stimulating factor (G- CSF)
Stimulates precursor cells for the type of WBCs known as granulocytes
pegfilgrastim (Neulasta)
Longer-acting form of filgrastim
Winter 2013

13. Hematopoietic Drugs (cont’d)
sargramostim (Leukine)
Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes
Granulocyte-macrophage colony- stimulating factor (GM-CSF)
Winter 2013

14. Hematopoietic Drugs (cont’d)
oprelvekin (Neumega)
Also classified as an interleukin (IL-11)
Stimulates bone marrow cells (megakaryocytes) that eventually become platelets
Winter 2013

15. Hematopoietic Drugs: Indications
Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy
Winter 2013

16. 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
Winter 2013

17. Hematopoietic Drugs: Indications (cont’d)
Also enhance RBC and platelet counts in patients with bone marrow suppression resulting from chemotherapy
Allow for higher doses of chemotherapy, resulting in the destruction of a greater number of cancer cells
Winter 2013

18. Hematopoietic Drugs: Adverse Effects
Usually mild
Fever
Muscle aches
Bone pain
Flushing
Others
Winter 2013

19. Hematopoietic Drugs: Epoetin
FDA warning
Increased adverse effects when used by patients with higher-than-normal hemoglobin
Heart attack
Heart failure
Stroke
Death
Winter 2013

20. 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
Winter 2013

21. Interferons (IFNs) Proteins with three basic properties
Antiviral
Antitumor
Immunomodulating
Used to treat certain viral infections and cancer
Winter 2013

22. 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
Winter 2013

23. 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
Winter 2013

24. 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
Winter 2013

25. Interferons: Adverse Effects
Flulike effects
Fever, chills, headache, myalgia
Dose-limiting adverse effect is fatigue
Other adverse effects
Anorexia
Dizziness
Nausea
Vomiting
Diarrhea
Winter 2013

26. Interferons (cont’d) Three major classes of IFNs Alpha Beta Gamma
Winter 2013

27. Interferons (cont’d)
Interferon alpha products: “leukocyte interferons”—produced from human leukocytes
Interferon Alpha-2a, Interferon Alpha-2b
Interferon Alpha-n3, Interferon Alphacon-1
Peginterferon Alpha-2a
Peginterferon Alpha-2b
Winter 2013

28. Interferons (cont’d) Interferon beta products
IFN beta-1a
IFN beta-1b
Interferon gamma products
Interferon gamma-1b
Winter 2013

29. Monoclonal Antibodies (MABs)
Used to target specific cancer cells
Minimal effect on healthy cells
Fewer adverse effects than traditional antineoplastic medications
Used to treat cancers and rheumatoid arthritis
Winter 2013

30. Winter 2013

31. Monoclonal Antibodies (MABs) (cont’d)
Cancer treatment
alemtuzumab (Campath)
bevacizumab (Avistatin)
cetuximab (Erbitux)
gemtuzumab ozogamicin (Mylotarg)
Other disease processes, including rheumatoid arthritis
adalimumab (Humira)
infliximab (Remicade)
natalizumab (Tysabri)
Winter 2013

32. 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
Winter 2013

33. Interleukins and Related Drugs
Beneficial antitumor action
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
Winter 2013

34. 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 and malignant melanoma
Under study for use in other types of cancer
Winter 2013

35. Interleukins: 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
Reversible after interleukin therapy is discontinued
Winter 2013

36. 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
Winter 2013

37. Interleukins (cont’d)
anakinra (Kineret)
IL-1 receptor antagonist
Used to control symptoms of rheumatoid arthritis
Winter 2013

38. Rheumatoid Arthritis
Autoimmune disorder causing inflammation and tissue damage in joints
Diagnosis primarily symptomatic
Treatment consists of NSAIDs and disease- modifying antirheumatic drugs
Winter 2013

39. Antirheumatoid Arthritis Drugs
Also known as disease-modifying antirheumatic drugs (DMARDs)
Slow onset of action—several weeks
May take 3 to 6 months to see full effects
Can have much more toxic adverse effects than NSAIDs
Antiinflammatory, antiarthritic, immunomodulating effects
Winter 2013

40. Antirheumatoid Arthritis Drugs (cont’d)
Methotrexate
etanercept (Enbrel)
abatacept (Orencia)
leflunomide (Arava)
Winter 2013

41. Antirheumatoid Arthritis Drugs (cont’d)
etanercept (Enbrel)
Used to treat rheumatoid arthritis (including juvenile RA) and psoriasis
Patients must be screened for latex allergy (some dosage forms may contain latex)
Onset of action: 1 to 2 weeks
Contraindicated in presence of active infections
Reactivation of hepatitis and TB have been reported
Winter 2013

42. Antirheumatoid Arthritis Drugs (cont’d)
abatacept (Orencia)
Used to treat rheumatoid arthritis
Caution if history of recurrent infections or COPD
Patients must be up-to-date on immunizations before starting therapy
May increase risk of infections associated with live vaccines
May decrease response to vaccines
Winter 2013

43. Nursing Implications (cont’d)
Teach patients to report signs of infection immediately
Sore throat
Diarrhea
Vomiting
Fever over 100° F
Winter 2013