Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 15 CANCER CHEMOTHERAPY
● Cardiotoxicity has not been reported in dogs treated
with mitoxantrone and it does not seem to worsen
mild doxorubicin-induced cardiotoxicity.
● Cats treated with mitoxantrone may experience gastrointestinal
toxicity. Fewer than 20% of cats demonstrated
vomiting, diarrhea or anorexia.
● Myelosuppression leading to sepsis occurs in approximately
10% of cats. The nadir of neutropenia in cats
is not known.
Known drug interactions
Heparin binds to anthracyclines; therefore, intravenous
lines to be used with mitoxantrone should be flushed
with saline only to avoid this interaction.
Idarubicin and epirubicin
Mechanism of action
Idarubicin and epirubicin are doxorubicin analogs that
induce DNA strand breakage via topoisomerase II- or
free radical-mediated damage.
Mechanism of drug resistance
Drug resistance is mediated by P-gp and mutations in
topoisomerase II.
of epirubicin, accounting for this difference in
metabolism.
Adverse effects
● The most common adverse effect of idarubicin is
anorexia, which occurs in 20% of cats.
● Leukopenia and vomiting are less common, but do
occur.
● Epirubicin causes myelosuppression in dogs and the
nadir of leukopenia occurs 6–10 d following
administration.
● Cardiotoxicity of epirubicin in dogs may be less
than that of doxorubicin.
Known drug interactions
No drug interactions have been identified for either
epirubicin or idarubicin in dogs and cats but in people,
cimetidine has been shown to decrease clearance of
epirubicin.
Contraindications and precautions
Co-administration of cimetidine (400 mg twice daily for
7 d starting 5 d before chemotherapy) increased the
mean AUC of epirubicin (100 mg/m 2 ) by 50% and
decreased its plasma clearance by 30% in humans.
Formulations and dose rates
Epirubicin is currently not available in the USA, although it is available
elsewhere. Idarubicin is available in the injectable form only. See
Table 15.3 for dose rates.
Pharmacokinetics
Unlike other anthracyclines, idarubicin has high oral
bioavailability and can achieve therapeutic levels with
oral administration. The LD 50 of epirubicin in dogs is
2 mg/kg or 38 mg/m 2 . In dogs, 90–95% of epirubicin is
excreted in urine 4 h after administration. This differs
from elimination in humans in whom epirubicin and
its major metabolites are eliminated through biliary
excretion and, to a lesser extent, by urinary excretion.
Dogs may lack an enzyme required for glucuronidation
OTHER ANTITUMOUR ANTIBIOTICS
Plicamycin, actinomycin D and bleomycin are antitumor
antibiotics isolated from Streptomyces spp. They
are used infrequently in veterinary patients but may be
useful in certain specific situations.
Plicamycin
Other names
Mithramycin, NSC-24559, aureolic acid
Clinical applications
Historically, plicamycin was used as an antihypercalcemic
agent in cases of malignancy or rodenticide-induced
hypercalcemia where hypercalcemia is refractory to
Table 15.3 Epirubicin and idarubicin
Idarubicin
Epirubicin
Species Cat Dog
Dosage 2 mg/d for 3 d every 3 weeks 30 mg/m 2 every 21 d
Route of administration Oral Intravenous
Clinical application
Maintenance of remission in feline lymphoma
Substitute for doxorubicin in lymphoma protocol
Single agent therapy of lymphoma
Substitute for doxorubicin in lymphoma protocol
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