McQuade, Rachel (2017) Chemotherapy-Induced Gastrointestinal Dysfunction and Enteric Neuropathy. PhD thesis, Victoria University.

Abstract

Colorectal cancer (CRC) is a leading cause of morbidity and mortality affecting more than 1.4 million people annually worldwide. Due to the aggressive and asymptomatic nature approximately 60% of CRC sufferers are diagnosed at or beyond stage III resulting in prognostic outlook relying heavily on the successful application of chemotherapeutic treatment. Chemotherapeutic agents oxaliplatin, 5-fluorouracil and irinotecan represent the backbone of CRC treatment, significantly enhancing tumour regression and patient survival. However successful application of these cytotoxic chemotherapies is hindered by undesirable neurological and gastrointestinal (GI) side-effects. Chronic GI side-effects often result in dose limitations and, in severe circumstances, cessation of anti-cancer treatment, presenting a constant challenge in efficient and tolerable treatment of CRC. It is believed that chemotherapy-induced GI side-effects are a direct result of intestinal mucositis; however adjacent systems such as the enteric nervous system have been overlooked. This thesis aims to uncover the effects of in vivo administration of anti-cancer chemotherapeutics oxaliplatin, 5-fluorouracil and irinotecan on the enteric nervous system and GI function, and examine the neuroprotective efficacy of a cytoprotective agent BGP-15.

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