Adverse events around cancer treatment in companion animals

Cancer treatment is often considered to be associated with adverse events (AEs) from reactions to drugs.

Giuffrida¹ performed a systematic review of the reporting of AEs in the treatment of cancer in companion animal research papers. A total of 168 articles that contained data for 6,132 animals were included in the study. Some aspects of AE data were poorly reported, including reasons for treatment discontinuation and death, and methods and time frame of ascertainment of AE. Industry funding improved the quality of AE reporting, and a single-arm design was also associated with a higher quality of reporting.

The author noted, as the standard of reporting of AEs in veterinary cancer trials is variable, AEs may be under-reported and it is recommended a higher standard of AE surveillance and reporting is adopted.

Hyperfibrinolysis clotting

Aminocaproic acid has been used to improve clotting – especially in cases of hyperfibrinolysis, the mechanism thought
to be responsible for bleeding tendencies in greyhounds.

Brown et al² performed a study to assess the effect of aminocaproic acid on clot strength and lysis in an in vitro model of hyperfibrinolysis. Five healthy adult dogs were given aminocaprioc acid orally at various doses, and blood samples taken at a number of time points. No adverse effects were noted.

A significantly higher clot strength as measured by thromboelastography was found in the hyperfibrinolysis model.

At all the doses tested, aminocaproic acid inhibited fibrinolysis and the authors concluded this drug may be helpful for prevention of fibrinolysis in vivo.

Tetralogy of Fallot

Tetralogy of Fallot is a rare congenital cardiac anomaly. In a retrospective case series, Chetboul et al³ described the clinical and echocardiographic features of 31 cases of dogs and cats with this condition.

Terriers were found to be the most common breeds affected and most cases had clinical signs at the time of diagnosis. A total of 52% of cases were cyanotic. Most ventricular septal defects were large and the severity of pulmonic stenosis was variable.

No significant difference in survival times was apparent between dogs and cats, with a median age of cardiac-related death at around two years.

A low-grade or absent heart murmur was associated with a shorter survival time. Most animals died of the condition at a young age and most had severe clinical signs at the time of diagnosis.

Pre-operative fasting

It is common practice to recommend a patient is starved from the night before a procedure requiring general anaesthetic. However, evidence exists that a shorter pre-operative fast may reduce the incidence of gastro-oesophageal reflux during anaesthesia.

Savvas et al⁴ performed a study in which 60 dogs were fed canned food 3 hours prior to premedication and 60 were fed 10 hours before premedication.

Oesophageal pH was monitored and a pH of less than four was considered to be a sign of gastro-oesophageal reflux. Three dogs that were fed 3 hours prior to premedication showed evidence of reflux, compared to 12 that were fed 10 hours prior to premedication. This difference was statistically significant and the authors suggested feeding a half ration of ordinary canine diet 3 hours prior to premedication may be useful in practice.

Collapse on exercise

A large number of possible causes of collapse on exercise exist. Border collie collapse is an episodic disorder, manifested by repeated episodes of abnormal gait or collapse during vigorous exercise.

Taylor et al⁵ surveyed the owners of 165 border collies with episodic collapse. Other conditions, such as systemic, cardiac and neurological diseases, were considered unlikely in these cases based on normal examination and lack of progression. Onset of signs occurred at a median age of two years.

A total of 68% of episodes occurred during retrieving and 24% during herding. High environmental temperature and excitement increased the likelihood of a collapsing event.

A total of 40 dogs had video recordings available and these showed typical features of border collie collapse, such as ataxia of all four limbs, altered mentation, increased hindlimb tone and falling to the side.

The authors noted these signs suggested border collie collapse may be an episodic diffuse CNS disorder.

Gliomas

Gliomas are malignant CNS tumours that tend to be poorly responsive to chemotherapy. Fraser et al⁶ performed a cross-sectional study to evaluate the expression of epidermal growth factor receptor (EGFR) – a target of treatment in human cancer trials – and Ki-67 labelling index (a prognostic indicator) in canine gliomas. A total of 31 canine glioma samples were assessed for EGFR and Ki-67 labelling index using immunohistochemistry.

EGFR expression was found in 52% of samples and Ki-67 expression in 90%. Both EGFR and Ki-67 expression was associated with increased tumour grade.

The authors noted EGFR may be a useful target for anti-cancer drugs in canine gliomas and particularly in gliomatosis cerebri.

Hepatic copper accumulation

Hepatic copper accumulation can lead to hepatitis, fibrosis and cirrhosis, and is hereditary in certain breeds, including Labrador retrievers. Diagnosis requires liver biopsy, and a blood test for a biomarker for hepatic copper accumulation would be useful to detect at-risk dogs.

Dirksen et al⁷ measured two copper metabolism proteins, Cu/Zn superoxide dismutase and copper chaperone for superoxide dismutase, in red blood cells in 15 Labrador retrievers that had normal or increased liver copper concentrations.

Both enzymes were reduced in dogs with high liver copper compared to those with normal liver copper levels. The authors concluded these tests have potential as new biomarkers to assist in early diagnosis, treatment and monitoring of copper-associated hepatopathy.

• Some of the medications mentioned in this article are not licensed for veterinary use.