Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial

Lynne M Howells, Chinenye O O Iwuji, Glen R B Irving, Shaun Barber, Harriet Walter, Zahirah Sidat, Nicola Griffin-Teall, Rajinder Singh, Nalini Foreman, Samita R Patel, Bruno Morgan, William P Steward, Andreas Gescher, Anne L Thomas, Karen Brown, Lynne M Howells, Chinenye O O Iwuji, Glen R B Irving, Shaun Barber, Harriet Walter, Zahirah Sidat, Nicola Griffin-Teall, Rajinder Singh, Nalini Foreman, Samita R Patel, Bruno Morgan, William P Steward, Andreas Gescher, Anne L Thomas, Karen Brown

Abstract

Background: Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anticancer properties.

Objectives: This 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).

Methods: Twenty-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.

Results: Addition 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).

Conclusion: Curcumin 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.

Keywords: FOLFOX chemotherapy; curcumin; curcuminoids; metastatic colorectal cancer; randomized controlled trial.

Copyright © American Society for Nutrition 2019.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) diagram showing study participation, random assignment, and PP completion for the CUFOX study. Values represent frequency of events. CUFOX, folinic acid/5-fluorouracil/oxaliplatin + 2 g oral curcumin/d; FOLFOX, folinic acid/5-fluorouracil/oxaliplatin; IMP, investigational medicinal product; PP, per protocol.
FIGURE 2
FIGURE 2
Efficacy outcomes for patients with metastatic colorectal cancer receiving either FOLFOX or CUFOX. Kaplan–Meier plots show (A, B) PFS and OS in per-protocol populations (n = 9 for FOLFOX, n = 15 for CUFOX) and (C, D) PFS and OS in those patients that did not go on to receive surgical intervention (n = 7 for FOLFOX, n = 16 for CUFOX). Survival time is shown in days. OS and PFS were compared between treatment arms using log-rank tests. CUFOX, folinic acid/5-fluorouracil/oxaliplatin + 2 g oral curcumin/d; FOLFOX, folinic acid/5-fluorouracil/oxaliplatin; OS, overall survival; PFS, progression-free survival.

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