Page 209 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

188 PART 3 Therapeutic Modalities for the Cancer Patient

Delayed acute effects from chemotherapy often include bone in the workplace has been addressed through the United States
marrow suppression and nausea, vomiting, and diarrhea. In the Department of Labor. 86
Chemotherapy must be administered in a quiet location with-
majority of instances these effects are self-limiting, and the inci-
VetBooks.ir dence of hospitalization is low. Table 12.2 reviews the general out distraction. Oral chemotherapy drugs should be intact; tablets
should never be split or crushed, and capsules should never be
therapeutic strategies for management of the most common types
of AEs experienced in companion animals after chemotherapy. 80 opened. Oral liquid preparations are not recommended because
Examples of potential cumulative and/or chronic toxicity of a risk of inaccurate dosing and environmental contamination
include hepatic dysfunction after multiple doses of lomustine if some of the medication is spit out. For intravenous (IV) che-
(CCNU), cardiac abnormalities after exceeding a safe cumula- motherapy, the smallest gauge and shortest length of catheter to
tive dose of DOX (dogs), and renal disease after cisplatin (dogs) accommodate therapy should be used, and it must be placed via a
or DOX (cats) use. Screening recommendations and strategies to “clean stick.” Only nonheparinized saline flushes should be used.
reduce the risks of such chronic effects have been developed and IV pumps should be avoided, except for multihour infusions (e.g.,
are incorporated into standard protocol procedures. It is critical cytosine arabinoside, dacarbazine). Chemical restraint should be
to the success of treatment that owners be thoroughly informed considered as-needed to ensure the safety of the patient and treat-
about monitoring guidelines for the signs of chemotherapy- ing personnel.
induced toxicity. Owner online educational resources are read- When dealing with chemotherapy spills, there is no universal
ily available at www.csuanimalcancercenter.org. It is advisable cleaning agent; however, use of a sodium hypochlorite (bleach)
to instruct the owner regarding monitoring and early responses solution, a strong detergent, and water will deactivate and remove
when his or her pet experiences nausea and vomiting, diarrhea, most hazardous drug residues. Alcohol will not deactivate che-
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or hematuria and it is important to inform the owner about how motherapy drugs and can spread contamination. Chemotherapy
to obtain an accurate body temperature. These “at home” aids drugs and their metabolites can be excreted in urine, feces, saliva,
will allow the clinician to assess the management options should and vomitus. Urinary levels of some active drugs may remain
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a concern arise. high for days after treatment, and fecal excretion may also be
expected. Contaminated excreta should be handled like a chemo-
Safety Concerns of Cancer Drug Therapy therapy spill.
Handling cytotoxic chemotherapy drugs is classified as an occu-
pational health hazard by the National Institute for Occupa- Pharmacologic Principles in Cancer Therapy
tional Safety and Health (www.cdc.gov/niosh/topics/hazdrug/). Pharmacokinetics
Cytotoxic chemotherapy drugs are mutagenic, carcinogenic, ter-
atogenic, abortifacient, and increase the risk of stillbirth. 81–84 Vet- Pharmacokinetic (PK) considerations in cancer drug therapy are
erinary hospitals that handle chemotherapy drugs must be aware important because of the relationship between drug exposure and
of and comply with evolving federal and state guidelines, and only pharmacodynamic (PD) response, be it efficacy or toxicity, that
trained personnel should be involved with handling these drugs is more exact than the relationship between drug dose and PD
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or the patients that receive them. Clients must also be informed response. PK considerations are also important with regard to
about potential hazards, particularly for women who are pregnant interactions with other drugs, herbal products, 90,91 and genetic
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or breastfeeding, and for young children. differences among breeds and individuals that can cause changes
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Chemotherapy should be stored, prepared, and used in desig- in drug exposure at a given dose. Cytotoxic chemotherapy is usu-
nated areas that are clearly labeled. Ideally, these areas should be ally dosed on an MTD-based schedule reflecting only acceptable
dedicated solely for these tasks, with access restricted for unau- toxicity and thus limits any informative role of drug half-life and
thorized personnel. Eating, drinking, smoking, chewing gum, effective therapeutic concentrations from initial dosing consider-
using tobacco, applying cosmetics, or storing food or drinks must ations. The most important PK parameters are those that have a
be prohibited in these areas. Chemotherapy ideally should be pre- relationship with either a response to therapy (efficacy) or toxic-
pared in a class II, type B2 biologic safety cabinet (BSC). This type ity, which is most often either the area under the plasma/serum
of BSC provides inward airflow, downward HEPA-filtered lami- concentration versus time curve (AUC) or the maximum drug
nal airflow, and HEPA-filtered exhausted air that is 100% venti- concentration achieved (C max ), illustrated in Fig. 12.4. The rela-
lated outside. The use of a closed-system transfer device (CSTD) tionships of AUC and C max in the clinical pharmacology of DOX
such as PhaSeal, Equashield, Chemoclave, or Onguard is recom- illustrate the complex associations with PK considerations. The
mended as well. A CSTD mechanically prevents the escape of C max during DOX infusion in humans is related to the incidence
drug or vapor out of the system into the environment and reduces of cardiotoxicity both in adult and pediatric patients, but is
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the risk of accidental needle puncture. These precautions reduce also associated with longer remissions in leukemia patients. A
environmental contamination, but do not obviate the need for relationship between AUC values and decreased white blood cells
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personal protective equipment (PPE). Double-gloving is recom- has also been established with DOX ; however, no clear relation-
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mended using powder-free latex or nitrile gloves that are chemo- ships between AUC and efficacy exist. These data have allowed
therapy rated by ASTM International standards. Gowns should be for adjustments in DOX dosing protocols such that intermediate
disposable, impermeable, closed-front style, and long-sleeved with infusion times (10–30 minutes) are utilized to decrease the C max
elastic or knit cuffs. Eye and face protection should be used when and thus cardiotoxicity, while still maintaining peak levels associ-
there is a high risk for splashes or aerosols, such as with intral- ated with effective therapy.
esional chemotherapy injections. Respiratory protection using a PK studies that relate drug exposure to responses are an impor-
fitted respirator with an N95 rating is required when engineering tant first step in establishing relationships that may be exploited
mechanisms cannot control exposure of an aerosolized drug (e.g., for dose modification based on patient characteristics or therapeu-
a drug spill). Guidelines for limiting exposure to hazardous drugs tic drug monitoring. These data are generally lacking for the drugs