Page 1302 - Small Animal Internal Medicine, 6th Edition

1274 PART XII Oncology

and constantly proliferating. Antiangiogenic drugs showed and relatively inexpensive (PhaSeal, Carmel Pharma, Colum-
promise in mouse studies but not in human or spontaneous bus, OH, and EquaShield, Port Washington, NY), which
VetBooks.ir animal tumor patients. limit operator and environmental drug exposure to almost
zero. If containment devices are not available, cytotoxic
Metronomic (from the Greek “metros,” in small constant
installments) chemotherapy is defined as the chronic admin-
or at a nearby small animal clinic with a sufficiently large
istration of chemotherapeutic agents at relatively low, mini- drugs can be reconstituted at a human hospital or pharmacy,
mally toxic doses and with no prolonged drug-free breaks. oncology caseload. Care should be taken to respect the
It is proposed to inhibit tumor growth primarily through storage half-life of reconstituted drugs, and they should be
antiangiogenic mechanisms, while significantly reducing administered to the patient as soon as possible after recon-
undesirable toxic adverse effects. Targeted molecular drugs stitution. A recent literature review (Chan et al., 2017)
such as toceranib (Palladia, Zoetis, Madison, NJ) and described storage recommendations for various chemother-
nonsteroidal antiinflammatory drugs (NSAIDs) appear to apy agents and can be used as a resource for chemotherapeu-
have antiangiogenic effects by targeting specific receptors. tic drug storage in practice. Drugs should be delivered in a
Metronomic chemotherapy is thought to exert its anti- clearly labeled, sealed plastic bag, and any handling of the
cancer activity mainly by inhibiting tumor angiogenesis. drugs should be performed while wearing the appropriate
However, immunomodulation appears to play a role in personal protective gear.
tumor response. T-regulatory lymphocytes (T REG ) have been Personal protective gear has been shown to all but elimi-
shown to be increased in several human, canine, and feline nate detectable occupational exposure to cytotoxic drugs
cancers, and appear to correlate with tumor progression and in human oncology nurses when combined with safe, con-
lack of treatment response. Several studies performed in servative handling practices. All personnel present during
tumor-bearing animals have shown that low-dose cyclo- chemotherapy administration to animal patients, including
phosphamide can increase antitumor immune response by veterinarians, technicians, and ward staff, must wear thick
decreasing numbers and inhibiting the suppressive functions latex chemotherapy gloves or two pairs of regular latex exam-
of T REG cells but also by increasing both lymphocyte prolif- ination gloves. The thickness of the gloves is more important
eration and memory T cells. Low-dose cyclophosphamide than the composition for barrier protection. Ideally, per-
also decreases numbers of circulating T REG in dogs. A third sonnel should also wear impermeable disposable gowns,
mechanism that appears to contribute to the effectiveness of eye protection, and particle-filtering face masks. All fluid
metronomic chemotherapy is the induction of tumor dor- lines should be primed before addition of cytotoxic drugs
mancy or tumor cell apoptosis. to reduce environmental contamination, and all potentially
The authors previously evaluated several metronomic contaminated supplies, including gowns, gloves, fluid bags,
chemotherapy protocols that combine an NSAID, low-dose lines, and so forth, should be disposed of in properly labeled
alkylators, and toceranib (Palladia) in dogs with spontane- biohazard bags or plastic sharps containers. Disposal of
ous neoplasms, which showed objective responses in patients material potentially contaminated with cytotoxic drugs may
with carcinomas and sarcomas. For metronomic chemo- be arranged through a local human hospital; alternatively,
therapy protocols, please see the Cancer Chemotherapy Pro- an Environmental Protection Agency–approved disposal
tocols table (p. 1337). facility should be located. Materials used in the preparation
and administration of chemotherapy should not be reused.
Patient waste, including urine and feces, should be disposed
SAFE HANDLING OF of similarly 24 to 48 hours after chemotherapy adminis-
ANTICANCER DRUGS tration, and personnel involved in the husbandry of these
patients should wear the previously recommended personal
Cytotoxic drugs have narrow therapeutic indices, with toxic protective gear when attending patients.
effects occasionally noted at the standard therapeutic Protocols for handling spills should be prepared in
dosages. Occupational exposure, as might occur in person- advance and posted in areas where patients may be receiving
nel who commonly administer these drugs, has been docu- chemotherapy. This area should be a designated area of the
mented in the literature; adverse effects, including headache, hospital with low traffic and minimal drafts; a stall may be
nausea, liver disease, and reproductive abnormalities, have selected for this purpose in equine hospitals. Isolation stalls
been reportedly associated with this exposure. As such, no will minimize exposure of personnel to chemotherapeutic
safe exposure level has been identified, and all possible mea- agents. Once the patient has received chemotherapy, its cage
sures to limit personnel exposure to cytotoxic drugs must be should be clearly identified with a notice that contains infor-
taken during their preparation and administration. mation about precautions to be taken during handling of the
Reconstitution of cytotoxic drugs for administration must animal and its wastes.
be performed in a biosafety level II vertical laminar airflow
hood. Although the cost for this equipment is not prohibi- Suggested Readings
tively expensive for a large veterinary hospital (≈$6000- Biller B. Metronomic chemotherapy in veterinary patients with
$10,000), this cost is currently not justified by the frequency cancer: rethinking the targets and strategies of chemotherapy. Vet
of use. Closed system transfer devices (CSTDs) are practical Clin North Am Small Anim Pract. 2014;44(5):817.