1. Chapter 20 Antineoplastic and Immunosuppressive Drugs Copyright © 2011 Delmar, Cengage Learning

2. Basic Terminology Anticancer drugs stop the cancerous activity of malignant cells –Also called antineoplastic agents and chemotherapeutic agents Characteristics of malignant cells include rapid cell division and growth, different rates of cellular drug uptake, and increased cellular response to selected anticancer drugs Some factors present in malignant cells are also found in normal cells –Rapid cell division and growth occur in cells of the GI tract, bone marrow, reproductive organs, and hair follicles Neoplasms are cancer cells that can spread from the site of origin to other areas of the body that are favorable for cell growth Copyright © 2011 Delmar, Cengage Learning

3. Cell Cycle Phases The five phases of the cell cycle: –G 1 : enzymes needed for DNA synthesis are produced –S: DNA synthesis and replication –G 2 : RNA and protein synthesis –M: mitosis phase –G 0 : resting phase Copyright © 2011 Delmar, Cengage Learning

4. Definitions Related to Antineoplastic Agents Growth fraction: percentage of cancer cells that are actively dividing –A high growth fraction occurs when cells are dividing rapidly –When tumors age and enlarge, their growth fraction decreases Doubling time: time required for the number of cancer cells to double –When tumors age and enlarge, their doubling time increases Copyright © 2011 Delmar, Cengage Learning

5. Administering Antineoplastic Agents Antineoplastic agents are often administered in various protocols known as combination therapy Calculation of antineoplastic drug doses is based on body surface area in square meters When administering antineoplastic agents, great care must be taken; refer to Table 20-2 in your textbook When administering antineoplastic agents IV, infuse unmedicated IV solution before and after administration of the drug to ensure that antineoplastic drug residues do not remain on the equipment Copyright © 2011 Delmar, Cengage Learning

6. Administering Antineoplastic Agents Pulse Dosing –A method of delivering some types of chemotherapeutic agents that produces escalating levels of drugs early in the dose followed by a dose free interval –Offers therapeutic advantages such as reduced dose frequency and greater compliance –Is the preferred way to administer some chemotherapeutic agents Copyright © 2011 Delmar, Cengage Learning

7. Guidelines for Handling Antineoplastic Agents OSHA recommends antineoplastics be prepared under a vertical laminar flow hood –The vertical laminar flow hood provides both product and operator protection by filtering incoming and exhaust air through a high efficiency air filter Use latex gloves to protect the skin Good hand-washing before and after drug preparation Copyright © 2011 Delmar, Cengage Learning

8. Guidelines for Handling Antineoplastic Agents Prevent contact of Antineoplastic agents with skin Goggles or a air filtration mask are recommended to protect eyes and mouth Wipe all external surfaces of bottles and syringes with alcohol Maintain record of all exposures during preparation, administration, clean-up, and spills Copyright © 2011 Delmar, Cengage Learning

9. Antineoplastic Agents Cell-cycle nonspecific (CCNS): –Alkylating agents cross-link DNA to inhibits its replication Examples include cyclophosphamide, cisplatin, chlorambucil, melphalan, and carboplatin –Antitumor antibiotics inhibit DNA, RNA, and protein synthesis Examples include doxorubicin, dactinomycin, and mitoxantrone Copyright © 2011 Delmar, Cengage Learning

10. Antineoplastic Agents Cell-cycle nonspecific (CCNS) (cont.): –Steroid drugs have anti-inflammatory effects, suppress bone marrow cells, reduce edema, and suppress tumor growth Examples include corticosteroids, estrogens, progestins, and androgens Copyright © 2011 Delmar, Cengage Learning

11. Antineoplastic Agents Cell-cycle specific (CCS): –Antimetabolites affect the S phase involving DNA synthesis Examples include methotrexate, 5-fluorouracil, cytarabine, and azathioprine –Alkaloids stop cancer cell division Examples include vincristine and vinblastine Copyright © 2011 Delmar, Cengage Learning

12. Antineoplastic Agents Biologic response modifiers (BRMs): used to enhance the body’s immune system; used in conjunction with antineoplastic protocols –Interferons are a group of proteins that have antitumor and antiviral effects; used to treat tumors and viral infections in cats There are three types of interferon: alpha, beta, and gamma –Colony stimulating factors (CSFs) stimulate the growth, maturation, and differentiation of bone marrow stem cells; have been used to treat neutropenia in dogs and cats An example is filgrastim Copyright © 2011 Delmar, Cengage Learning

13. Antineoplastic Agents Biologic response modifiers (BRMs) (cont.): –Interleukins are a group of chemicals that play various roles in the immune system and promote the replication of antigen-specific T cells –Acemannan is a potent stimulator of macrophage activity and is used to treat fibrosarcomas and mast cells in dogs and cats –Monoclonal antibodies have cytotoxic effects on tumor cells and are used in conjunction with other antineoplastic agents Copyright © 2011 Delmar, Cengage Learning

14. Antineoplastic Agents Immunosuppressive drugs work by interfering with one of the stages of the cell cycle or by affecting cell messengers –Cyclosporine inhibits the proliferation of T-lymphocytes; used for managing KCS in dogs and immune-mediated skin disorders –Azathioprine affects cells in the S phase of the cell cycle and also inhibits T- and B-lymphocytes; used mainly in dogs for immune-mediated disease –Cyclophosphamide interferes with DNA and RNA replication, disrupting nucleic acid function; has been used for immune-mediated diseases Copyright © 2011 Delmar, Cengage Learning

15. Antineoplastic Agents Enzymes –L-asparaginase is an example of an enzyme used in the treatment of cancer –L-asparaginase works by hydrolyzing asparagines into aspartic acid and ammonia –Cancer cells need an exogenous source of asparagine for survival; normal cell can synthesize asparagine –Side effects of L-asparaginase include pain at the injection site, hypotension, and diarrhea Copyright © 2011 Delmar, Cengage Learning

16. Antineoplastic Agents Enzyme Inhibitors –Offer another approach to treating tumor cells by controlling their growth –Toceranib is a tyrosine kinase inhibitor used to treat mast cell tumors in dogs –Is an oral tablet tablet used to manage adverse reactions such as neutropenia, diarrhea, anorexia, lethargy, vomiting –Hands should be washed when handling tablets –Gloves should be worn when cleaning up body fluids from dogs on Toceranib Copyright © 2011 Delmar, Cengage Learning

17. Adverse Reactions to Antineoplastic Agents Antineoplastic agents can cause adverse reactions in rapidly dividing normal cells Some of these adverse reactions are listed in Table 20-3 of your textbook Copyright © 2011 Delmar, Cengage Learning