Abstract
BackgroundThe need for low toxicity adjuncts to standard care chemotherapy in inoperable colorectal cancer, with potential to improve outcomes and decrease the side-effect burden, is well recognised. Addition of the low toxicity diet-derived agent, curcumin (the active ingredient of turmeric), to standard oxaliplatin-based therapy has shown promise in numerous pre-clinical studies.Methods/DesignThis study is the first to combine daily oral curcumin with standard care FOLFOX-based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy in colorectal cancer patients with inoperable liver metastases: the CUFOX trial. CUFOX comprises a Phase 1 dose-escalation study (3 + 3 + 3 design) to determine an acceptable target dose of curcumin with which to safely proceed to a Phase IIa open-labelled randomised controlled trial. Thirty three participants with histological or cytological confirmation of inoperable colorectal cancer will then be randomised to oxaliplatin-based chemotherapy with the addition of daily oral curcumin at the target dose determined in Phase I, or to standard care oxaliplatin-based chemotherapy alone (recruiting at a ratio of 2:1).DiscussionPrimary outcome measures will be the determination of a target dose which is both safe and tolerable for long-term administration to individuals in receipt of first-line oxaliplatin-based chemotherapy for inoperable colorectal cancer. Secondary outcome measures will include observation of any changes in neuropathic side-effects of chemotherapy, improvement to progression-free or overall survival and identification of putative efficacy biomarkers in plasma.The results will be disseminated via presentation at national and international conferences, via publication in appropriate peer-reviewed journals and via the Cancer Research UK/Department of Health Experimental Cancer Medicine Centre Network. This trial has full ethical and institutional approval, and commenced recruitment in February 2012.Trial registrationClinicalTrials.gov (NCT01490996, registered 7th December 2011), European Drug Regulating Authorities (EudraCT 2011-002289-19, registered 13th May 2011), UKCRN ID#10672.
Highlights
The need for low toxicity adjuncts to standard care chemotherapy in inoperable colorectal cancer, with potential to improve outcomes and decrease the side-effect burden, is well recognised
Primary outcome measures will be the determination of a target dose which is both safe and tolerable for long-term administration to individuals in receipt of first-line oxaliplatin-based chemotherapy for inoperable colorectal cancer
We have previously reported that curcumin augments the effect of oxaliplatin against Colorectal cancer (CRC) cell lines, and restores efficacy in a cellular model of chemo-resistance [17]
Summary
The need for low toxicity adjuncts to standard care chemotherapy in inoperable colorectal cancer, with potential to improve outcomes and decrease the side-effect burden, is well recognised. Background and rationale Colorectal cancer (CRC) is the fourth most common cancer worldwide. It carries the second highest cancerrelated mortality in Western countries with a lifetime incidence of ~1 in 15 [1,2]. Up to a fifth of CRC patients will present with metastatic disease, typically in the liver [3], and half of those undergoing resection for primary disease will develop metastases. The majority of these patients are not amenable to curative surgery [4] and experience a 5-year survival rate of less than 10%. Approximately 40% of such cancers display chemo-resistance from the outset and eventually all will fail to respond
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