Cancer Chemotherapy Nancy Stark RN, DNP, CNAA BC NURS: 6200 School of Nursing Cancer Drug Therapy Benefits Cure Palliation Prolongation of useful life Types Cytotoxic drugs Non-cytotoxic drgus Hormonal therapy Immunotherapy Targeted drugs Characteristics of neoplastic cells Persistent proliferation Invasive growth Metastasis Immortality Growth Fraction Growth fraction ? ratio of proliferating cells to cells in G0 High growth fraction ? large percent of proliferating cells in G1, few in G0 Low growth fraction ? large percent of cells in G0, few in G1 ? cytotoxic drugs are more toxic to cancers with a high growth fraction Which type of cancer will respond better to chemotherapy? a. Solid tumor b. Disseminated cancers Obstacles to Successful Chemotherapy Toxicity to normal cells Cure requires 100% cell kill Absence of truly early detection Solid tumors respond poorly Drug resistance Heterogeneity of tumor cells Limited drug access to tumor cells Strategies for Maximizing Chemotherapy Benefits Intermittent chemotherapy Combination chemotherapy Optimizing dosing schedules Regional drug therapy Intermittent Administration Combination Therapy Key point: Cytotoxic chemotherapeutic drugs do not have selective toxicity ? they can harm the host cell Toxicities are associated with normal tissues that have a high growth fraction Major Toxicities of Chemo Bone marrow suppression Digestive tract injury Nausea and vomiting Alopecia Reproductive toxicity Hyperuricemia Local injury ? vesicant extravasation other Myelosuppression Neutropenia = infection, loss of neutrophils Anemia = fatigue, loss of erythrocytes Thrombocytopenia = bleeding, loss of thrombocytes (platelets) Treatment ? colony stimulating factors Granulocyte colony stimulating factor (Filgrastim) Granulocyte macrophage colony stimulating factor (Sargramostim) -> increase granulocytes Erythropoietin (Epogen) -> increase RBC Oprelvekin (Neumega) -> increase platelets What are the nursing implications associated with the care of someone who has: Neutropenia Anemia Thrombocytopenia What is a nadir? What is a normal neutrophil count? In general, when is a client who has received chemotherapy at greatest risk for infection? Are there any differences in infection symptoms in a client with lack of neutrophils? At what count, should chemotherapy be evaluated for continued administration? Digestive Tract Injury Stomatitis ? inflammation of the oral mucousa ->can lead to ulceration Treatment ? oral hygiene, bland diet, topical anesthetics, analgesics, antifungals, glucocorticoids to decrease inflammmation, palifermin (Kepivance) Diarrhea ? injury results in impaired absorption of fluids, nutrients Treatment ? high fiber, constipating foods Nausea and Vomiting Other Toxicities Alopecia Reproductive toxicity Hyperuricemia Local injury from extravasation of vesicant Drug specific toxicities carcinogenesis What action should the nurse take, if a vesicant chemotherapeutic agent infusion infiltrates? Remove the IV What combination of drugs is especially effective in chemotherapy induced nausea and vomiting? Zofran, Emend, Decadron What chemotherapeutic agents are known to have severe emetogenic potential? Chemo Drug List: Cytotoxic Anticancer Drugs 1: Cyclophosphamide Cisplatin ? severe emetic potential Methotrexate Doxorubicin Vincristine Vinblastine Non-cytotoxic Anticancer Drugs 2: Glucocorticoids Leuprolide Tamoxifen Anastrazole Imatinib Bevacizumab Anticancer Drugs I Cytotoxic Drugs: Act directly on cancer cell as well as the healthy cell to produce cell kill Most - disrupt processes related to synthesis of DNA or precursors Some - block mitosis, or disrupt protein synthesis (With exception of asparaginase) ? all cytotoxic agents act on cells undergoing replication Cell Cycle Phase: Cell cycle phase-specific drugs ? effective only during a specific phase of the cell cycle (not active against G0 cells) ? must be in blood for long time, must be there when cell goes through specific phase Cell cycle phase-nonspecific drugs ? affect cells during any phase of the cycle including G0 Cytotoxic Agent Classes: Alkylating agents Platinum compounds Antimetabolites Antitumor antibiotics Mitotic inhibitors Topoisomerase inhibitors Miscellaneous cytotoxic drugs Alkylating Agents: Cells killed because of the alkalinization of DNA Cycle Phase ? non-specific, so more toxic to proliferating cells Drug resistance ? Common ADR ? Occurs in high growth fraction tissues 3 subclasses: Nitrogen mustards, nitro-ureas, others, most + vesicants Prototype: Cyclophosphamide (Cytoxan, Neosar) Pharmacokinetics ? prodrug, activated in liver Uses: broad spectrum- lymphomas, myeloma, solid tumors of head, neck, ovary, breast. prodrug- converted to active form in liver Routes: PO, IV (not a vesicant) Common adverse effects: bone marrow suppression, N/V, alopecia, hemorrhagic cystitis Platinum Compounds: Most Cell-cycle phase nonspecific Prototype: Cisplatin (Platinol-AQ) Cisplatin analogs: Carboplatin Oxaliplatin Uses: metastatic testicular and ovarian cancers, advanced bladder, off-label in lung, head and neck Mechanism of action: bind with DNA and form cross links at two sites (guanine) -> miscoding, inhibition of DNA replication Cell cycle non-specific Route: IV Adverse effects: kidney damage (hydration and diuretics), N/V, neurotoxicity, ototoxicity, bone marrow suppression Antimetabolites: Structural analogs of natural metabolites Three classes of antimetabolites: Folic acid analog Pyrimidine analogs Purine analog Cell cycle phase specific ? most affect S phase Lack of these metabolites disrupts critical metabolic processes that are needed for metabolic fx. Prototype: Methotrexate (Rheumatrex, Trexall) Uses: acute lymphocytic leukemia (childhood), lymphomas, head, neck, osteogenic sarcomas (RA, Psoriasis, Chrones Dz) Mechanism of action: prevents conversion of folic acid to active form ->inhibits dihydrofolate reductase -> DNA synthesis disrupted Leucovorin rescue ? enhances Methotrexate active cell uptake, allows normal cells to uptake folic acid, but prevents malignant cells so they take up methotrexate Resistance ? has developed Routes: PO, IM, IV, intrathecal Adverse effects: bone marrow, pulmonary infiltrates/fibrosis, oral, GI ulcerations, enteritis, N/V, renal damage with high doses, pregnancy should be delayed for 6 mos after tmt. Antitumor Antibiotics: Not used to treat infections, are used to treat CA, have direct interaction with DNA Two groups of antitumor antibiotics: Anthracyclines ? damage cardiac tissue Nonanthracyclines ? don?t damage heart Prototype: Doxorubicin (Adriamycin) Uses: solid tumors and disseminated cancers, lymphomas, leukemias, sarcomas, lung, stomach, breast, ovary, testes and thyroid cancers Mechanism of action: binds to DNA and distorts DNA structure ->DNA synthesis inhibited Routes: IV (vesicant) Adverse effects: does cause cardiotoxicity r/t cumulative dose 550mg/m2(watch for dysrhythmias / ECG changes, delayed HF d/t cardiomyopathy mos to yrs), N/V, red color to urine, sweat, bone marrow suppression Mitotic Inhibitors: Vinca alkaloids: Vincristine [Oncovin] Vinblastine [Velban] Vinorelbine [Navelbine] Taxoids: Paclitaxel [Taxol] Docetaxel [Taxotere] Vinca Prototypes: Vincristine (Oncovin), Vinblastine (Velban): Uses: Hodgkins, non-Hodgkins lymphoma, ALL, Kaposi?s sarcoma, breast cancers Pharmacokinetics of Vincas: poor to no penetration of blood-brain barrier (not good for brain CA), hepatic metabolism, biliary excretion Mechanism of action: M-phase specific, blocks microtubule assembly Route: IV Adverse effects: Vincristine ? peripheral neuropathy ? lower manifests as decr periph reflexes, weakness, paresthesia, sensory nerves, autonomic nerves, constipation, urinary hesitance. Nearly ALL have these symptoms, about 50% will have elimination probls, not much myelosuppression effect Vinblastine ? significant bone marrow suppression, signif effects on myelosuppression A cell-cycle phase non-specific drugs can affect cells during any phase of the cycle including G0? True Which class of drugs can result in fatal cardiotoxicities such as heart failure and dysrhythmias? Anthracyclines (Adriamycin) Which mitotic inhibitor has the adverse effect of peripheral neuropathy? Vincristine Which drug Inhibits dihydrofolate reductase, an enzyme needed in the activation of folic acid? Methotrexate Which drug Forms cross-links between and within strands of DNA? Cisplatin Which drug A prodrug that undergoes conversion to an active form in the liver, and causes the alkylation of DNA? Cyclophosphamide Anticancer Drug II classes: Hormonal agents Biologic response modifiers Targeted drugs ? bind with specific molecules that drive tumor growth, so extremely selective, so although they harm the CA, they leave host cells alone Cell phase non-specific Lack characteristic toxicities of cytotoxic agents A Note about Glucocorticoids: Pharmacologic doses in cancer treatment Prototypes: Prednisone (Prelone), &Dexamethasone (Decadron): Uses: drugs used in combo for lymphomas and leukemias Other uses: management of complications: reduce n/v, cerebral edema, reduce nerve pain from compression from inflammation, suppress hypercalcemia in steroid tumors, increase wellbeging by increasing appetite Short term acute use ? minimum toxicities Long term use ? many adverse effects Prostate Cancer: Advanced cancers ? cause pharmacologic androgen deprivation by either: Lower testosterone production Block testosterone receptors Tmt: surgery, irradiation, brachytherapy, poss. androgen deprivation Androgen deprivation is not a cure Adverse effects: reduced libido, decreased muscle mass, increased fat deposits, decreased bone mass/fracture risk Prototype: Leuprolide (Lupron): Use: Prostate cancer Mechanism of action: suppress production of androgens by the testes, gonadotropin-releasing hormone (GnRH) agonist Often combined with an androgen receptor blocker (Flutamide- Eulexin) Route: SQ, IM or implant Adverse effects: hot flushing, impotence, loss of libido, reduction of muscle mass, osteoporosis Breast Cancer: Death rate is declining!! Prevention for high risk ? Tamoxifen (Nolvadex) Treatment regimen ? surgery -> irradiation -> Cytotoxics -> Hormonals Hormonals (work only w/ + estrogen receptor CA): Antiestrogens ? blood estrogen receptors Aromatase inhibitors ? block estrogen production SERM ? Tamoxifen: Prototype: Tamoxifen (Nolvadex) GOLD standard ? breast cancer treatment Estrogen receptor positive cancers Mechanism of action: blocks estrogen receptors prevents receptor activation by estradiol ? decline in number of cells Pharmacokinetics: absorbed in GI, metabolized by liver, eliminated in feces, long ½ life Adverse effects: increased risk of endometrial cancer, thromboembolic events, fluid retention, hot flushes, menstrual irregularities Aromatase Inhibitor - Anastrazole Prototype: Anastrazole (Arimidex) Use: postmenopausal women with early breast cancer, or advanced breast cancer Mechanism of action: inhibits aromatase reduced estrogen production Route: oral Adverse effects: asthenia, nausea, headache, hot flushes, joint musculoskeletal pain (25% pts), increased risk of osteoporosis Biologic Response Modifiers, Immunostimulants: Alter host response to CA by stimulating natural immune response, cells differentiate into non-proliferative forms, enable host to better tolerate myelosuppressive actions of anticancer drugs Interferon alfa-2a and interferon alfa-2b (Roferon A, Intron A) Aldesleukin (interleukin-2) [Proleukin] BCG vaccine [TheraCys, TICE BCG, Pacis] Targeted Drugs: Bind with specific molecules that drive tumor growth. Many are antibodies directed at specific antigens found primarily on tumor cells Ideally, would demonstrate selective toxicity Targeted Drug - Angiogenesis Inhibitor Prototype: Bevacizumab (Avastin) Use: colon or rectal cancer Action: antibody that binds with vascular endothelial growth factor -> prevents factor from binding with receptors -> prevents blood vessel formation -> inhibits tumor growth ->can?t kill existing tumor cells Adverse effects: GI perforation, disruption of wound healing, hypertensive crisis, thromboembolism, pulmonary hemorrhage Targeted Drugs ? BCR-ABL Tyrosine Kinase Inhibitor Prototype: Imatinib (Gleevec) Use: chronic myeloid leukemia (CML) & GI stromal tumors Mechanism of action: inhibits BCR-ABL tyrosine kinase ->suppresses proliferation of CML cells, promotes apoptosis (body?s natural means of killing cells) Route: oral Adverse effects: N/V, rash, headache, fatigue, musculoskeletal complaints, fluid retention, neutropenia, thrombocytopenia A client taking Avastin needs to undergo an elective surgical procedure, with consideration of the wound healing adverse effects of the drug, how long before surgery should the drug be stopped? 28 days
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