Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial

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.

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…Phase I clinical trials have shown safety, tolerability, and nontoxicity of curcumin even at high doses (8 g/day) but exhibited poor bioavailability in humans (Sharma et al, 2004;Kanai et al, 2013). Despite bioavailability challenges, clinical trials with curcumin either alone or in combination as an anticancer agent have shown efficacy against several disease sites such as breast (Bayet-Robert et al, 2010), prostate (Mahammedi et al, 2016), pancreatic (Epelbaum et al, 2010;Kanai et al, 2013), colorectal (Sharma et al, 2004;Carroll et al, 2011;Irving et al, 2015;James et al, 2015), and hematological malignancies (Ghalaut et al, 2012). Latest information on various preclinical and clinical anticancer trials using curcumin is reviewed in Doello et al (2018).…”

In vitro additive antitumor effects of dimethoxycurcumin and 5‐fluorouracil in colon cancer cells

“…A preliminary study from our lab showed that DMC is an effective antitumor agent that downregulates survivin and upregulates E‐cadherin in colon cancer cells . Moreover, recent studies reported that curcumin combined with FOLFOX chemotherapy was clinically safe and tolerable and capable of preventing colon cancer growth . Therefore, combining DMC with chemotherapy should have potent antitumor effects in colon cancer cells.…”

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

“…Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a polyphenolic compound isolated from Curcuma longa , that has demonstrated a wide range of biological activities; anti-inflammatory, 10–14 anti-oxidative, 15–19 antibacterial, 20–26 rheumatoid arthritis, 27–30,12,31–33 Alzheimer’s, 34–42 psoriasis, 43,44 and diabetes. 45–53 Curcumin has been investigated for its anti-cancer properties for cancers such as lung, 54–58 ovarian, 59–65 colorectal, 66–73 and pancreatic. 74–81 …”