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Chapter 20
Antineoplastic and Immunosuppressive Drugs
Copyright © 2011 Delmar, Cengage Learning
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
Cell Cycle Phases
• The five phases of the cell cycle:
–
–
–
–
–
G1: enzymes needed for DNA synthesis are produced
S: DNA synthesis and replication
G2: RNA and protein synthesis
M: mitosis phase
G0: resting phase
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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
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
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
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
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
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
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
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
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
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
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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
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
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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
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