Abstract
ABSTRACTBackgroundCurcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anticancer properties.ObjectivesThis phase IIa open-labelled randomized controlled trial aimed to assess safety, efficacy, quality of life, neurotoxicity, curcuminoids, and C-X-C-motif chemokine ligand 1 (CXCL1) in patients receiving folinic acid/5-fluorouracil/oxaliplatin chemotherapy (FOLFOX) compared with FOLFOX + 2 g oral curcumin/d (CUFOX).MethodsTwenty-eight patients aged >18 y with a histological diagnosis of metastatic colorectal cancer were randomly assigned (1:2) to receive either FOLFOX or CUFOX. Safety was assessed by Common Toxicity Criteria-Adverse Event reporting, and efficacy via progression-free survival (PFS) and overall survival (OS). Quality of life and neurotoxicity were assessed using questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Functional Assessment of Cancer Treatment-Gynecologic Oncology Group-Neurotoxicity). Plasma curcuminoids were determined with liquid chromatography (LC) electrospray ionization tandem mass spectrometry and CXCL1 by ELISA.ResultsAddition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention-to-treat population, the HR for PFS was 0.57 (95% CI: 0.24, 1.36; P = 0.2) (median of 171 and 291 d for FOLFOX and CUFOX, respectively) and for OS was 0.34 (95% CI: 0.14, 0.82; P = 0.02) (median of 200 and 502 d for FOLFOX and CUFOX, respectively). There was no significant difference between arms for quality of life (P = 0.248) or neurotoxicity (P = 0.223). Curcumin glucuronide was detectable at concentrations >1.00 pmol/mL in 15 of 18 patients receiving CUFOX. Curcumin did not significantly alter CXCL1 over time (P = 0.712).ConclusionCurcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer. This trial was registered at clinicaltrials.gov as NCT01490996 and at www.clinicaltrialsregister.eu as EudraCT 2011-002289-19.
Highlights
Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anti-cancer properties
We have previously established that curcumin significantly increased apoptosis and decreased proliferation in colorectal cancer cell lines when combined with oxaliplatin [11], which was recapitulated in vivo using the HCT116 xenograft mouse model [12]
We present here the results of a Phase IIa open-labelled, two-armed, randomized controlled trial, comparing efficacy of first-line folinic acid/5-fluorouracil/oxaliplatin chemotherapy (FOLFOX) chemotherapy alone versus FOLFOX plus curcumin (CUFOX), in patients with colorectal metastases
Summary
Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anti-cancer properties. Colorectal cancer remains a significant contributor to morbidity and mortality in the UK, with up to 20% of patients presenting with metastatic disease [1] Surgical resection in those individuals with anatomically isolated metastases can significantly improve survival outcomes, but is feasible in less than 30% of patients [2]. Whilst targeted therapies have the facility to provide clear benefit in specific patient cohorts, there is a need to investigate alternative strategies using low toxicity, multi-target agents. Re-purposed drugs and diet-derived agents with well-characterised pharmacokinetic and toxicological profiles potentially offer improved quality of life and clinical benefit, yet clinical data is sparse. One such diet-derived agent is curcumin, derived from the spice turmeric
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