This prospective pilot study will examine whether the previously reported effects of NSAIDs on colorectal cancer may be modulated through alterations in tissue gene expression, up regulation of local immune cell infiltrates or down-regulation of the systemic inflammatory response.
Bowel cancer is the second commonest cause of death from cancer in the UK. Of patients who have an apparently curative operation, half unfortunately suffer disease recurrence and die before 5 years. Clearly more research is required to improve outcomes in this condition. Most current research focuses on antitumour strategies, however the reaction of the patient (host) to the tumour is also important. The host inflammatory responses to the cancer are likely to represent part of this host-tumour relationship. Inflammation plays an important role in predicting patients who will die. Currently it is not known whether antiinflammatory drugs have any effect on cancer related inflammation detected in the blood or in/around the tumour. Aims: We hope to demonstrate that tumour related inflammation in bowel cancer can be altered using anti- inflammatory drugs. This may form the rationale for the use of antiinflammatory drugs to improve prognosis in colorectal cancer patients undergoing surgery. Methods: This pilot study will investigate whether simple antiinflammatory drugs can alter markers of inflammation both in the blood and in/around the tumour. Patients having bowel cancer surgery will be prescribed one of two anti-inflammatory drugs (aspirin 75mg once daily or ibuprofen 400mg three times daily) for 2 to 3 weeks prior to their operation. Blood and tumour samples before and after the treatment will be analysed. If the study's aims are met and cancer-related inflammation can be altered prior to surgery, then a larger scale drug trial will be proposed to demonstrate reduced cancer recurrence and improved survival.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
60
Glasgow Royal Infirmary - Walton Building
Glasgow, United Kingdom
Klintrup-Makinen immune score
To evaluate the local inflammatory effects associated with down-regulation of the systemic inflammatory response prior to curative surgery as measured by Klintrup-Makinen immune score
Time frame: Approx 4 weeks (post-treatment and surgery)
Systemic inflammatory response
Comprehensive assessment of the systemic inflammatory response prior to curative surgery as measured by C-reactive protein (CRP), differential white cell count, albumin and cytokines (IL-1, 6,8 and 10, TNF-alpha)
Time frame: Approx 4 weeks (post-treatment and surgery)
Assessment of gene inflammatory profile
Time frame: Approx 4 weeks (post-treatment and surgery)
Local inflammatory response
Immunohistochemical analysis of immune cells infiltrates in colonic and tumour tissue will be performed quantitatively. Cell surface antigens evaluated include CD4+, CD8+, CD68+, CD45RO+ and FOXP3+.
Time frame: Approx 4 weeks (post-treatment and surgery)
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