Pilot Study to Investigate the Physiological Effects Associated With Down-regulation of Host-tumour Inflammatory Responses in Colon Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Klintrup-Makinen immune score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged 18 to 75 years old
- •histologically confirmed colon cancer
- •evidence of systemic inflammation (C-reactive protein >10mg/l)
- •candidate for elective primary curative resection
排除标准
- •Age <18yrs or >75yrs
- •emergency presentation
- •rectal cancer
- •distal metastatic disease at presentation
- •provision of neo-adjuvant chemo-radiotherapy
- •long-term use of aspirin or anti-inflammatory medications (NSAIDS, or steroids
- •hypersensitivity to product or excipients or evidence of previous hypersensitivity reactions such as asthma, rhinitis, angioedema or urticaria in response to aspirin, ibuprofen or other NSAID
- •intolerance of NSAIDs/ aspirin due to allergy or side effects
- •active peptic ulcer disease
- •previous history of recurrent gastrointestinal bleeding or bleeding/perforation secondary to previous NSAID use
- •previous treatment for gastrointestinal cancer
- •alcohol excess (above recommended guidelines)
- •chronic renal impairment
- •moderate to severe heart failure
- •hepatic impairment
研究组 & 干预措施
Aspirin
20 patients randomised to aspirin 75mg PO once daily
干预措施: Aspirin (Drug)
Ibuprofen
20 patients randomised to ibuprofen 400mg PO three times daily
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Klintrup-Makinen immune score
时间窗: Approx 4 weeks (post-treatment and surgery)
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
次要结局
- Systemic inflammatory response(Approx 4 weeks (post-treatment and surgery))
- Assessment of gene inflammatory profile(Approx 4 weeks (post-treatment and surgery))
- Local inflammatory response(Approx 4 weeks (post-treatment and surgery))