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Curcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer.

. 2019 Jul; 149(7): 1133–1139.
Published online 2019 May 27. doi: 10.1093/jn/nxz029
PMCID: PMC6602900
PMID: 31132111

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

Associated Data

Supplementary Materials

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

Acknowledgments

The authors’ responsibilities were as follows—LMH, GRBI, BM, WPS, AG, and KB: designed the research; LMH, COOI, ZS, NG-T, RS, NF, and SRP: conducted the research; SB: performed the statistical analyses; HW: analyzed the data; LMH: wrote the manuscript; COOI, GRBI, SB, HW, RS, WPS, AG, ALT, and KB: reviewed the manuscript; ALT: provided clinical oversight and was the trial principal investigator; and all authors: read and approved the final manuscript.

Notes

Supported by Hope Against Cancer grants 01 (to LMH) and 02 (to ALT), The Royal College of Surgeons grant 01 (to GRBI), Bowel Disease Research Foundation grant 01 (to GRBI), Cancer Research UK grant C325/A13101 (to KB), and by Cancer Research UK with the Department of Health via Experimental Cancer Medicine Centre grants C325/A15575 and C10604/A25151 (to WPS).

Author disclosures: LMH, COOI, GRBI, SB, HW, ZS, NG-T, RS, NF, SRP, BM, WPS, AG, ALT, and KB, no conflicts of interest.

Supplemental Table 1 and Supplemental Figures 1 and 2 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/.

Abbreviations used: AE, adverse event; CUFOX, curcumin + 5-fluorouracil + folinic acid + oxaliplatin; CXCL1, C-X-C motif chemokine ligand 1; FOLFOX, folinic acid + 5-fluorouracil + oxaliplatin; FU, fluorouracil; GRO, growth-regulated oncogene; ITT, intention to treat; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PP, per protocol.

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