Predicting Gastrointestinal Adverse Events in Dogs Treated with Chemotherapeutic Medication

Abstract: Despite significant advances in the treatment of cancer in canine patients, gastrointestinal toxicity still remains a relatively common finding after chemotherapeutic treatment. These adverse events may cause a fundamental reduction in the patient’s quality of life. To improve the well-being of the patients, and to minimize the risk of adverse events following chemotherapy, the mechanisms and reasons behind the development of adverse events have to be understood. There are several possible factors that might affect the risk of developing chemotherapy-induced gastrointestinal toxicity, however, there are currently no standardized methods for reviewing, mapping or measuring these factors within the field of study. The use of questionnaires, in combination with non-invasive biomarkers, could therefore potentially be a stress-free and favourable way of investigating the correlations between chemotherapy and gastrointestinal adverse events as well as a way of predicting which animals that are at risk for gastrointestinal toxicity. A prospective study at University Animal Hospital (UDS) in Uppsala, Sweden, was performed with the ambition of investigating the connection between chemotherapeutic treatment and the development of gastrointestinal toxicity. The main aim of this study was to find possible influential factors leading to the development of gastrointestinal adverse events after chemotherapeutic treatment. The study was divided into two questionnaire-based parts with questions directed to owners of dogs with a cancer diagnosis. The first questionnaire reviewed potential influential factors in the everyday life and diet of the dog which could be related to the development of chemotherapy-induced adverse events. This questionnaire also examined the frequency of gastrointestinal events as well as concurrent illnesses and treatments. The second questionnaire focused on the occurrence and assessment of gastrointestinal toxicity in dogs treated with chemotherapeutic medication based on VCOG-CTCAE (version 2). A total of eight dogs with cancer of different ages, sexes, and breeds were included in the study. According to the owners, 87% (n=7) of the dogs had experienced some form of mild gastrointestinal disturbance without the need for supportive therapies during the last year. Three of the eight canine patients continued with chemotherapeutic treatment and could be assessed through the second questionnaire. In total, 67% (n=2) dogs experienced different grades of gastrointestinal adverse events (loss of appetite, diarrhoea) within three to five weeks after their first chemotherapeutic treatment. The questionnaires show promise to be used in studies with similar aims, possibly in combination with the analysis of biomarkers. However, due to the small study population, the results from this study may not be representative of a larger population. It is not possible to determine whether the gastrointestinal events that were reported in this study were caused by the cytostatic agents or if they had another aetiology. Therefore, further studies must be performed regarding potential influential factors as well as to investigate the actual clinical utility of the questionnaires. Further studies regarding the use of non-invasive biomarkers such as calprotectin and/or gut microbiota may also be of importance to examine the association with the development of gastrointestinal adverse events.