Final report submitted to Bowel Disease Research Foundation September 2016
Project title: A novel approach to enhancing the effectiveness of chemotherapy: a biomarker driven study combining curcumin with FOLFOX in metastatic colorectal cancer.
Researcher:Mr Glen RB Irving.
Co-researchers:Mr David P Berry, Mr Andrew Miller, Dr Lynne Howells, Dr Karen Brown, Prof William P Steward
Bursary awarded:£30,000
Institution administering funding:University Hospitals Leicester and Dept. Cancer Studies University, of Leicester.
The award from the BDRF was essential in providing funding for encapsulation and pharmacist-approved (QP) release of the Investigational Medicinal Product, curcumin, for the clinical trial entitled ‘A phase I/IIa study combining curcumin (Curcumin C3-Complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer – the CUFOX study’.This trial is registered at
Thiswas undertaken as part of a PhD project by Dr Glen Irving. The PhD was awarded to Dr Irving in 2013. However, the trial has continued to run over the intervening time, and we are pleased to report that the last patient finishes on the trial in October 2016. This means that we can now analyse this data, and hope that a further publication will arise from this work in late 2017.
We have conducted an interim analysis of the data for the BDRF, in order that the funders can see the overall achievements that their original funding has contributed to.
In brief, the CUFOX study was the first study to combine daily oral curcumin (a derivative of the spice turmeric) with standard care FOLFOX-based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy which is used in bowel cancer patients whose cancer has spread to the liver, and cannot be removed by surgery.The CUFOX study consisted of a phase 1 dose-escalation study to determine an acceptable dose of curcumin (consisting of 1, 2 or 4 capsules per day) which could then be safely used in a phase IIa randomised controlled trial (RCT). In phase IIa, participants who were confirmed to have inoperable bowel cancer were given eitheroxaliplatin-based chemotherapy with the addition of daily oral curcumin at the dose determined in phase I, or standard care oxaliplatin-based chemotherapy alone. Our primary aim in this study, was to determine a target dose of curcumin which was both safe and tolerable for long term administration to patients receiving first-line oxaliplatin-based chemotherapy for inoperable bowel cancer. We also sought to determine whether there were any changes to chemotherapy-induced side effects or improvement to survival.
Further details regarding how this trial was conducted can be found in the publication:
Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): studyprotocol for a randomised control trial. Irving et al. Trials (2015) 16:110.
Results to the phase I component can be found in the publication:
Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. James et al. Cancer Letters 364 (2015) 135–141.
Whilst we cannot yet fully analyse the final results of the trial, we have conducted an interim analysis on the first 18 patients that participated in the CUFOX study, which are briefly described below:
Out of the first 18 patients, 13 received curcumin with their chemotherapy (CUFOX) and 5 received chemotherapy only (FOLFOX). Patients on CUFOX received 1 week of curcumin prior to commencing chemotherapy. Seven of 13 patients (54%) experienced no adverse events when taking curcumin on its own, with the remaining patients experiencing low grade events which generally related to bowel disturbances. When patients started on chemotherapy, all experienced adverse events and curcumin may have contributed to the diarrhoea that is often observed with chemotherapy.
Progression-free survival was compared between the 2 arms at 7 months of follow-up. Median progression free survival was significantly longer in the CUFOX patients compared to the FOLFOX patients(7.6 months vs 5.5 months).
We can conclude that curcumin alone has minimal side effects, but may contribute to chemotherapy-induced diarrhoea in patients receiving FOLFOX chemotherapy. The small numbers of participants at this point do not allow conclusions to be drawn regarding progression free survival. However, curcumin can be considered to be safe and tolerable in conjunction with FOLFOX-based chemotherapy.
We would again like to thank the BDRF and its supporters for providing the funding which initiated this research project.
Kind regards,
Lynne Howells, Leicester Experimental Cancer Medicine Centre.