Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 15 CANCER CHEMOTHERAPY
Clinical applications
In cases of vincristine intolerance, vinblastine is typically
substituted in combination chemotherapy protocols.
Careful monitoring must be undertaken when
making this substitution because life-threatening myelosuppression
may occur. Use of vinblastine has been
described in dogs with lymphoma and tonsillar squamous
cell carcinoma. Vinblastine is currently being
investigated as a treatment for canine mast cell tumors
along with prednisone and appears to have efficacy in
this disease. Optimum treatment protocols have yet to
be defined.
Formulations and dose rates
Vinblastine must be stored at 2–8°C to maintain potency and will
degrade if exposed to light.
DOGS
• The standard dosage of vinblastine is 2 mg/m 2 IV bolus every
10–14 days. Intrathecal administration of vinblastine to dogs
resulted in severe neurological impairment and death in onethird
of dogs
Known drug interactions
There are no known major drug interactions.
Vinorelbine
Other names
Navelbine, KW-2307, CAS71486-22-1
Clinical applications
Vinorelbine is currently under investigation in veterinary
oncology. In a phase I clinical trial, modest efficacy
was found in dogs with macroscopic bronchoalveolar
carcinoma.
Formulations and dose rates
DOGS
• 15–18 mg/m 2 appears to be the range of maximum tolerated
dose in dogs. A starting dosage of 15 mg/m 2 as an intravenous
infusion over 5 min has been recommended
CATS
• Use of vinorelbine has not been reported in cats
Pharmacokinetics
Using tritiated vinblastine, a biphasic clearance of vinblastine
from plasma of normal dogs was identified.
Initial rapid clearance occurred in 24–30 min and slower
elimination over 4–7 h. Up to 80% of drug was protein
bound. The majority of vinblastine was excreted in bile
and metabolized in the intestinal tract. A smaller amount
of unmetabolized vinblastine is excreted in urine. Vinblastine
is poorly absorbed orally.
Adverse effects
● Although the dose-limiting effect of vinblastine is
myelosuppression, with the nadir of leukopenia in
dogs occurring 4–7 days following drug administration
(mean occurrence of neutropenia, day 5), toxicity
is typically mild. In a study of dogs with mast cell
tumors, the most common toxicity was mild thrombocytopenia.
Neutrophil reconstitution takes place
7–14 days after administration. Overall hematological
toxicity was 10% of all complete blood counts.
● Gastrointestinal signs, such as vomiting and constipation,
may also be seen.
● Like vincristine, vinblastine causes local tissue necrosis
if the drug is extravasated. Management of a
suspected extravasation is identical to that of
vincristine.
● Vinblastine is not believed to have major effects on
wound healing.
Pharmacokinetics
Vinorelbine is widely distributed into tissues except the
central nervous system and is highly (90%) protein
bound. Unchanged drug has a terminal half-life of
34.5 h in dogs. Clearance is 1.2 L/h/kg and has a volume
of distribution of 49.6 L/kg. Especially high concentrations
are achieved in lung tissue and the concentration
in mammary tissue exceeds those in plasma. The chief
mechanism for excretion of vinorelbine is via the feces.
Urinary excretion represents less than 30% of drug
elimination.
Adverse effects
● Myelosuppression occurred in 32% of dogs treated
with vinorelbine in a phase I clinical trial.
● Gastrointestinal toxicity (vomiting, diarrhea,
anorexia) occurred in 16% of dogs in a phase I
clinical trial.
● Skin necrosis if the drug is extravasated has been
reported in humans.
Known drug interactions
There are no known major drug interactions.
Etoposide
Other names
NCS-141540, VP-16-213, epipodophyllotoxin, EPE-ethylidene
Lignan P
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