Translating curcumin into clinical practice for treatment of metastatic colorectal cancer: the CUFOX trial. Doctoral (PhD) Thesis. University of Leicester, UK. Degree Awarded date: April 26, 2017.Iwuji, COO
Colorectal cancer is also called bowel cancer, colon cancer, or rectal cancer, is any cancerous growth that affects the colon and the rectum. 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.
Objective:
To investigate the safety and feasibility of administering curcumin with standard oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.
Methods:
The study was conducted in two phases
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 II was an open-labeled, two-armed, randomized 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
The 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 Phase IIa of this study.
