Page 1313 - Small Animal Internal Medicine, 6th Edition

CHAPTER 77 Complications of Cancer Chemotherapy 1285

decreasing the risk of SHC is calculating the total dose of both. In a recent study of 50 dogs receiving CCNU, increased
2
cyclophosphamide for a dog to receive (i.e., 200-250 mg/m liver enzyme activity occurred in 84% of dogs receiving
VetBooks.ir in the typical multiagent protocol for lymphoma) and split- CCNU alone and in 68% of dogs on concurrent Denamarin
(Nutramax, Lancaster, SC) at therapeutic doses. Dogs receiv-
ting administration over 2-4 days. In a recent study, splitting
administration of cyclophosphamide over 3 days without
concurrent furosemide administration in dogs with lym- ing CCNU alone had significantly greater increases in ALT,
aspartate aminotransferase, alkaline phosphatase, and biliru-
phoma, 0/57 dogs to develop SHC (these dogs also experi- bin, and a significantly greater decrease in serum cholesterol
enced an 82% complete remission, suggesting that the concentrations than dogs receiving concurrent Denamarin.
efficacy was likely not affected by this dosing regimen) (Best Dogs receiving CCNU alone were significantly more likely
et al., 2013). Additionally, a recent study evaluating the use to have treatment delayed or discontinued because of
of concurrent furosemide during metronomic administra- increased ALT activity (Skorupski et al., 2011). For this
tion of cyclophosphamide also subjectively decreased the reason, Denamarin should be used concurrently with CCNU
prevalence of SHC to 3.6% (versus up to 32%) (Chan et al., when possible.
2016). Dogs with immune-mediated disorders receiving chronic
Clinical signs of sterile hemorrhagic cystitis are similar to azathioprine therapy rarely develop increases in liver enzyme
those of other lower urinary tract disorders and include pol- activities that respond to discontinuation of the drug.
lakiuria, hematuria, and dysuria. Urinalysis typically reveals
blood and mildly to moderately increased numbers of white
blood cells but no bacteria. Treatment of this complication NEUROTOXICITY
consists of discontinuing the cyclophosphamide, forcing
diuresis, diminishing the inflammation of the bladder wall, Anticancer agent–induced neurotoxicity is also extremely
and preventing secondary bacterial infections. The cystitis rare in dogs and cats. Neurotoxicosis occurs infrequently in
resolves in most dogs within 1 to 4 months after the cyclo- dogs receiving 5-FU, although it is common in cats (for this
phosphamide is discontinued. The author administers furo- reason, this drug should not be used in cats). Neurotoxicity
semide at a dosage of 2 mg/kg PO every 12 hours for its can also occur in dogs and cats that ingest 5-FU intended for
diuretic effects, prednisone at a dosage of 0.5 to 1 mg/kg PO human use (i.e., prescribed for the owners). Clinical signs
every 24 hours for its antiinflammatory (and diuretic) effect, occur shortly (3-12 hours) after ingestion of the drug and
and an ST combination at a dose of 13 to 15 mg/kg PO every consist primarily of excitation and cerebellar ataxia, resulting
12 hours to prevent secondary bacterial contamination. If in death in approximately one third of the dogs and in most
the clinical signs worsen despite this approach, the instilla- cats. Neurotoxicity was also documented in 25% of dogs
tion of 1% formalin solution in water into the bladder can receiving a combination of actinomycin D, 5-FU, and cyclo-
be attempted. Gross hematuria resolved within 24 hours and phosphamide (the CDF protocol) for the management of
did not recur in two dogs thus treated. The intravesical infu- metastatic or nonresectable carcinomas at one of the authors’
sion of a 25% to 50% dimethylsulfoxide solution may also clinics. This prevalence is considerably higher than that seen
alleviate the signs of cystitis in dogs. in association with the use of 5-FU in combination with
other drugs and may be a result of drug interactions.
HEPATOTOXICITY
PULMONARY TOXICITY
Chemotherapy-induced hepatotoxicity is extremely rare in
dogs and cats. With the exception of the hepatic changes Chemotherapy-induced pulmonary toxicity appears to be a
induced by corticosteroids in dogs, methotrexate, cyclophos- rare adverse effect in dogs and cats. Lomustine has been
phamide, lomustine, and azathioprine (Imuran, Burroughs associated with the development of pulmonary fibrosis in
Wellcome, Research Triangle Park, NC) have been impli- cats. This was seen after a high cumulative dose; however, it
cated as or confirmed to be hepatotoxins in dogs. In our was associated with death after an episode of acute respira-
experience, the hepatotoxicity caused by anticancer drugs in tory distress in one patient.
small animals is of little or no clinical relevance, with the Similarly, there are multiple reports of pulmonary fibrosis
exception of lomustine. in 5% to 15% of dogs treated with Tanovea; in most patients,
A recent report describes a low prevalence of hepatotoxic- it was fatal. Anecdotally, the concurrent use of prednisone
ity (<10%) in dogs receiving lomustine (CCNU) for lym- may help decrease this specific toxicity. For this reason, we
phoma or mast cell tumors. The authors clinics have recommend not using Tanovea in breeds predisposed to
documented marked increases in alanine transaminase development of pulmonary fibrosis, mainly West Highland
(ALT) activities (>1000 IU/L) and mild increases in alkaline White Terriers and other terrier breeds; we also recommend
phosphatase (ALP) activities (<500 IU/L) within 3 weeks of having baseline thoracic radiographs on dogs receiving this
starting lomustine therapy in several dogs. Most dogs had agent.
decreases in the ALT and ALP concentrations after lengthen- Bleomycin has also been associated with pulmonary tox-
ing the dosing interval, decreasing the individual dosage, or icity in humans, leaving this as a potential concern for