Chemotherapy Biotherapy & Targeted Therapies MiKaela Olsen RN, MS, OCN Oncology and BMT Clinical Nurse Specialist Objectives State the dose limiting toxicity of chemotherapy Describe the mechanism of action of 2 different biotherapy drugs State the theory behind targeted therapies Why Use Chemotherapy? Characteristics of malignant cells Uncontrolled growth Decreased ability to repair DNA damage Need for systemic treatment Metastatic tumors Cancers that are systemic by nature 1 Goals of Chemotherapy Cure = No evidence of disease: Normal life span Control = Increase in survival and quality of life Palliation = Increase in comfort Affect of Chemotherapy on Dividing Cells Interferes with all dividing cells Cell division cycle Cell cycle specificity Specific Non-specific 2 Alkylating Agents Cell cycle non-specific Destroys DNA by causing cross-linking of strands during replication Examples: Mechlorethamine (Nitrogen Mustard) Cyclophosphamide Cisplatin Dacarbazine 3 Anti-tumor Antibiotics Cell cycle non-specific Interferes with DNA and RNA synthesis Examples: Doxorubicin Daunorubicin Bleomycin Mitomycin Antimetabolites Cell cycle specific (S phase) Block DNA synthesis by substituting for normal enzymes or other cellular components Examples: Fluourouracil Methotrexate Cytarabine Nitrosureas Cell cycle non-specific Cross the BBB Sterility Second malignancies Examples: BCNU, CCNU 4 Plant Alkaloids Cell cycle specific (M phase) Block mitosis by interfering with the integrity of the mitotic apparatus Examples: Vincristine Etoposide Paclitaxel Hormones and Hormone Antagonists Cell cycle non-specific Interfere with cellular division by altering the intracellular environment Examples: Corticosteroids Megestrol acetate Tamoxifen Luprolide Chemotherapy Side Effects 5 Chemotherapy Adverse Effects: Myelosuppression Mechanism of Occurrence Potential problems Leukopenia: Infection Thrombocyyptopenia: Bleeding Anemia: Fatigue At risk populations Myelosuppressive chemotherapy regimens Previous/concurrent myelosuppressive therapies Hematologic malignancies Source of infection Cardiopulmonary compromise ABSOLUTE NEUTROPHIL COUNT (ANC) Polys + Bands X WBC = ANC 100 Example: WBC = 4.5, Polys = 77, Bands = 3 77 + 3 X 4.5 = 100 80% X 4.5 = 3600 normal count 6 ANC AND RISK OF INFECTION 1,000 - 1,500 Minimal Risk 500 - 1,000 Moderate Risk < 500 Severe Risk CLINICAL MANIFESTATION Fever > 38oC (100.4o F) Reliable & often only sign of infection If extremely neutropenic, they may not be able to manifest the usual sign Chemotherapy Adverse Effects: Nausea and Vomiting Mechanism of occurrence PttPatterns Acute Delayed Anticipatory 7 Chemotherapy Adverse Effects: Nausea and Vomiting Potential Problems Dehydration Inadequate nutritional intake FtiFatigue At Risk Populations Emetogenic chemotherapy drugs History of nausea/vomiting Gastrointestinal/pelvic tumors Other medications (e.g. opioids, antibiotics) Emetogenic Potential of Select Chemotherapy Drugs Cisplatin Highest Dacarbazine Mechlorethamine Cyclophosphamide Doxorubicin/Daunorubicin Cytarabine Paclitaxel Etoposide Methotrexate Bleomycin Vincristine Lowest Fluorouracil Hormones 8 Chemotherapy Adverse Effects: Mucositis/Stomatitis Mechanism of Occurrence Potential Problems Pain Decreased food and fluid intake Increased risk for infection At risk populations Causative agents Intensive treatment regimens History alcohol/tobacco use Poor oral hygiene Head and neck tumors Chemotherapy Adverse Effects: Peripheral Neuropathies Mechanism of occurrence Potential problems Discomfort (pain, hyperesthesias) Increased risk of injury At risk populations Causative agents History of alcoholism or diabetes 9 Chemotherapy Adverse Effects: Renal Toxicity Mechanism of occurrence Potential problems Electrolyygte wasting Decreased ability to clear toxins/drugs At risk populations Causative agents (chemotherapy, antibiotics) Dehydration Preexisting renal disease Chemotherapy Adverse Effects: Cardiac Toxicity Mechanism of Occurrence Potential problems AtiititlActivity intolerance Congestive heart failure At risk populations Causative agents Children and elderly Pre-existing heart disease Chemotherapy Adverse Effects: Pulmonary Toxicity Mechanism of occurrence Potential problems Shortness of breath/DOE Activity intolerance Oxygen dependence At risk populations Causative agents Concurrent radiation therapy Pre-existing lung disease Primary or metastatic cancer History of smoking 10 Chemotherapy Adverse Effects: Fatigue Mechanism of occurrence Potential problems Activity tolerance Decreased treatment tolerance At risk populations Intensive treatment regimens Impaired activity tolerance prior to treatment Chemotherapy Adverse Effects: Alopecia Mechanism of occurrence Potential Problems Alteration in self concept At risk populations Causative agents Intensive treatment regimens Safe Handling of Hazardous Drugs What is a hazardous drug? Any drug which poses a significant risk to healthcare workers because of a potential to cause ttititeratogenic, mutagenic, carcinogenic or reproductive toxicity as well as other serious organ damage. Includes antineoplastic agents, as well as some biologic, anti-viral and anti-infective agents. 11 Safe Handling of Hazardous Drugs How might I be exposed to hazardous drugs? Healthcare workers can be exposed to hazardous drugs during preparation, transportation, administration, disposal of administration equipment, or disposal of body excreta from patients who have received hazardous drugs. Decreasing Risk of Exposure to Hazardous Drugs Wear protective gown and gloves when handling hazardous drugs or contaminated body fluids/excreta. Change gloves and wash hands before and after working with hazardous drugs. Wear goggles or facial splash guard when there is risk of splashing of drug or body fluids. Avoid hand to mouth or eye contact while working with hazardous drugs or contaminated body fluids. Chemotherapy Pretreatment Assessment Patient knowledge of: Disease and treatment plan Reason for using chemotherapy Specific agents to be administered Laboratory data Complete blood count with WBC differential Liver function test Renal function test 12 Chemotherapy Pretreatment Assessment History and Physical Assessment Side effects of previous treatments Signs/symptoms of infection Nutritional status Integrity of skin and mucosal barriers Cardiopulmonary status Energy level Emotional response to disease and treatment Social support Biotherapy Biological therapy is the therapeutic use of agents derived from biologic sources and/or affecting biologic responses. Also called “immunotherapy” and “biotherapy.” Modifies the body’s biologic/immune response resulting in therapeutic effects. Types Interferons Interleukins Hematopoietic Growth Factors 13 Immune System Review Complex system of cells and creation of antibodies Retains memory of previous encounters with immunogens and mounts responses on new challenges Differentiates between “self” and “foreign” In many cancers, may not recognize the cancer as “foreign” and/or the immune system does not act against it Some biological therapies stimulate the immune system to attack cancer. Hematopoietic Growth Factors Hematopoietic Growth Factors (HGFs) – proteins that interact with specific receptors to regulate the production, maturation, and function of blood cells. Usually used to ameliorate side effects of chemotherapy, although some are under investigation for anti-tumor properties. 14 Hematopoietic Growth Factors Agent Function Indication G-CSF Stimulates production, differentiation, Neutropenia Filgrastim (Neupogen®), Amgen and maturation of neutrophils Pegfilgrastim Stimulates production, differentiation, Neutropenia (Neulasta®), Amgen and maturation of neutrophils GM-CSF Stimulates production of both Neutropenia Sargramostim (Leukine®), Berlex granulocytes and macrophages Erythropoietin alpha Stimulates red blood cell production Anemia (Procrit®), OrthoBiotech; (Epogen ®), Amgen Interleukin-11 Stimulates platelet production Thrombo- Oprevelkin cytopenia (Neumega®), Wyeth-Ayerst Darbepoetin alfa Stimulates erythropoiesis Anemia (Aranesp®), Amgen Interferons: Biological Activities Antiviral action Inhibition of oncogenes Regulation of tumor cell growth; limitation of proliferation Immunomodulation Interferons: Cancer Therapy Name & manufacturer FDA-Approved Uses Intron® A Malignant melanoma Hairy cell leukemia (IFN-2b, recombinant) AIDS-related Kaposi’s sarcoma [Schering] Lymphoma Roferon®-A Hairy cell leukemia AIDS-related Kaposi’s sarcoma (IFN- 2a, recombinant) Chronic myelogenous leukemia [Roche Laboratories] Intron® A, Schering; Roferon®-A, Roche Laboratories 15 Interleukins: Biological Activities •Autocrine action (T helper cells) •Monocyte/macrophage activation •Promotion of cell division and release of mediators (T cells) •Activation and promotion of cell division (B cells) •Activation of Natural Killer (NK) cells Interleukin-2: Indications/ Administration Interleukin-2 Renal cell cancer [Aldeskeukin] Metastatic melanoma Subcutaneous Proleukin® (Chiron) Standard regimen, Interleukin-2: 600,000 IU/kg (0.037 mg/kg) administered every 8 hours by a 15-minute IV infusion for a maximum of 14 doses. Following 9 days of rest, schedule is repeated for another 14 doses, for maximum of 28 doses per course, as tolerated. During clinical trials, doses were frequently withheld for toxicity. Because of the possible severity of high-dose side effects, administration of high-dose