58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

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58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio Barbara E. Kitchell DVM, PhD, Dipl ACVIM, Michigan, USA Chemotherapy: well known drugs for standard therapies and for new therapies Sabato, 8 Marzo 2008, ore 12.20 56
58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio Cancer is recognized to be the leading cause of death in dogs and cats over 10 years of age. As veterinarians become more successful in managing general health issues in geriatric patients, the incidence of cancer inevitably increases. Systemic therapy for cancer traditionally requires the use of cytotoxic chemotherapeutic agents that target rapidly dividing cell populations. Therefore, common adverse effects seen with chemotherapy use are related to damage to the cells of the body that have rapid and obligatory patterns of cell replication, such as bone marrow cells and gastrointestinal epithelium. Drug-specific and speciesspecific adverse effects are also of significant concern. This lecture will provide an overview of anticancer drugs commonly used in veterinary medicine. Before discussing the drugs themselves, it is important to note that anticancer cytotoxic drugs are potential mutagens and teratogens, adding a significant biohazard potential for staff administering the compounds, and for clients exposed to treated animals. Appropriate biohazard guidelines should be followed when anticancer chemotherapeutic agents are prescribed in veterinary medicine. ANTICANCER ALKYLATING AGENTS The alkylating agents are cytotoxic due to their ability to contribute alkyl groups to biologically important macromolecules such as DNA and proteins. Alkylating agents are classified as being either monofunctional or bifunctional, based on the number of reactive sites. The DNA adducts and cross-linkages caused by alkylation injury prevent DNA replication and ultimately result in cell death. The effects of alkylating agents are not cell-cycle phase specific. Mechanisms of cellular resistance to alkylating agents include altered cellular uptake, increased production of nucleophilic substances such as sulfated compounds, and increased DNA repair. CYCLOPHOSPHAMIDE Cyclophosphamide is the most commonly used alkylating agent worldwide in human and veterinary oncology. It was synthesized in 1958 and is used most often as a part of combination chemotherapy protocols for a wide variety of cancers, as well as being an immunosuppressive agent for treatment of autoimmune diseases. Mechanism of action Cyclophosphamide is classified as a bifunctional alkylating agent. The 7- N position of guanine is the preferred target for attack by this drug. Effects 57
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58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

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