Translating curcumin into clinical practice for treatment of metastatic colorectal cancer : the CUFOX trial

• Main Author: Iwuji, Chinenye Oluchi Obiageri
• Other Authors: Howells, Lynne ; Brown, Karen
• Published: University of Leicester 2017
• Subjects: 616.99
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713373

Palliative treatment of metastatic colorectal cancer provides an overall median survival rate of approximately 21 months, with response rates of less than 60%. Curcumin is a low molecular weight polyphenol derived from the spice turmeric that inhibits carcinogenesis in vitro and in vivo via multi-targeted mechanisms. A clinical study was established investigating the safety and feasibility of administering curcumin with standard oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer and in parallel biomarker analysis was conducted to identify potential biomarkers of efficacy and toxicity. Methods: Phase I was a dose escalation phase using the traditional escalation rule (3+3+3) design to establish the maximum target dose of curcumin. Phase IIa was an open-labelled, two-armed, randomised controlled feasibility trial. Patients received standard oxaliplatin and 5-FU chemotherapy with or without the maximum target dose of curcumin established in Phase I. Biomarker studies were conducted involving measurement of miR-122, curcumin/curcuminoids and DNA platination in patient plasma samples, and proteomic analysis of treated explant media from patient-derived colorectal liver metastasis. Results: Phase I dose escalation was successfully completed with thirteen patients receiving curcumin plus standard oxaliplatin-based chemotherapy up to the target dose of 2 grams daily with no significant issues identified with toxicity or feasibility. Eighteen patients had been recruited into Phase IIa at the time of this report with no notable safety concerns. Changes in miRNA and curcumin/curcuminoid levels were successfully measured in patient plasma samples. Explant culture analysis showed proteins involved in apoptosis, angiogenesis and inflammation/immune response were selectively upregulated following treatment with CUFOX. Conclusion: Addition of curcumin to standard FOLFOX chemotherapy up to a dose of 2 grams daily has shown good tolerability, feasibility and no safety concerns across Phase I and IIa of this study. Potential biomarkers for future investigation have been identified.