Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 15 CANCER CHEMOTHERAPY
Pharmacokinetics
The half-life of actinomycin D is 47 h in the dog. The
drug distribution phase is estimated to be 3 h. There is
rapid tissue uptake and excretion is via the biliary and
urinary tracts. Although actinomycin D has high lipid
solubility, no appreciable concentration of drug is
detectable in the central nervous system because of its
high molecular weight.
Adverse effects
● The most common toxicity with actinomycin D is
gastrointestinal. Vomiting immediately following
administration or vomiting 3–5 d following administration
occurs in one-third of dogs.
● Myelosuppression is uncommon and the nadir of
leukopenia occurs 5–7 d after drug administration.
● Drug extravasation results in soft tissue necrosis.
● Radiation recall is theoretically possible but has not
been described in veterinary patients.
Known drug interactions
There are no known drug interactions.
Bleomycin
Other names
NSC-125066, BLM 2
Clinical applications
Use of bleomycin has been described in squamous cell
carcinoma, lymphoma and other carcinomas. Its high
cost and short duration of effect limit its usefulness in
veterinary patients.
Pharmacokinetics
In normal beagles, bleomycin exhibits biphasic plasma
elimination characteristics. The elimination half-life following
IV injection is 1.0 h and after IM injection 1.1 h.
The volume of distribution in the central compartment
after IV administration is 0.125 L/kg. Bleomycin concentrates
in the skin and lung, accounting for some of
the clinical toxicity and efficacy.
Adverse effects
● Chronic administration in dogs results in interstitial
pneumonitis, which is a potentially fatal doselimiting
toxicity.
● Cutaneous toxicity has also been described as footpad
ulceration, nail deformities, pressure point sores and
alopecia. Prior chemotherapy or radiation therapy
may potentiate adverse effects.
● Myelosuppression is rare and mild, as are the gastrointestinal
toxicities.
Known drug interactions
No clinically significant drug interactions have been
reported.
PLATINUM ANALOGS
The platinum analogs are inorganic compounds that
have an antitumor activity that is cell cycle phase nonspecific.
Cisplatin was the first inorganic compound
used as a chemotherapeutic agent in veterinary medicine
but another platinum analog, carboplatin, is rapidly
replacing cisplatin in clinical use because administration
is more convenient.
Mechanism of action
Damage to DNA is the major mechanism of bleomycin
cytotoxicity. Bleomycin also causes lipid peroxidation
and oxidative metabolism of RNA. Bleomycin has a
greater effect in the M and G 2 phases of the cell cycle.
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Cisplatin
Other names
Mechanism of drug resistance
Increased bleomycin inactivation, decreased intracellular
drug accumulation and increased cellular DNA
repair of damage have been identified as mechanisms of
bleomycin resistance.
Formulations and dose rates
After reconstitution, the drug is stable for 4 weeks at 4°C. 1 unit of
bleomycin is equivalent to 1 mg.
DOGS, CATS AND FERRETS
• 10–20 U/m 2 SC or IV once a week, not to exceed 200 mg/m 2
NSC-119875, cis-diamminedichloroplatinum (II), DDP, CACP
Clinical applications
Cisplatin is indicated primarily for treatment of canine
osteosarcoma. Its efficacy as a single drug therapy for
osteosarcoma has been well documented. Despite
reports suggesting improved efficacy when cisplatin is
used in combination with other drugs such as doxorubicin,
the optimum adjuvant chemotherapy regimen for
dogs with osteosarcoma has not been determined.
Other indications, more anecdotally, include squamous
cell carcinoma, ovarian carcinoma, thyroid and
nasal adenocarcinoma and mesothelioma. Intracavitary
cisplatin infusions have been used to manage abdominal
and thoracic effusions. Initial reports suggested useful