58° Congresso Nazionale SCIVAC: Oncologia veterinaria

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
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