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

doi:10.1093/jn/nxz029

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

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

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.

Original language	English
Pages (from-to)	1133-1139
Number of pages	7
Journal	Journal of Nutrition
Volume	149
Issue number	7
DOIs	https://doi.org/10.1093/jn/nxz029
State	Published - 1 Jul 2019
Externally published	Yes

Keywords

Curcumin
Curcuminoids
FOLFOX chemotherapy
Metastatic colorectal cancer
Randomized controlled

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10.1093/jn/nxz029

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Howells, L. M., Iwuji, C. O. O., Irving, G. R. B., Barber, S., Walter, H., Sidat, Z., Griffin-Teall, N., Singh, R., Foreman, N., Patel, S. R., Morgan, B., Steward, W. P., Gescher, A., Thomas, A. L., & Brown, K. (2019). Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial. Journal of Nutrition, 149(7), 1133-1139. https://doi.org/10.1093/jn/nxz029

@article{ce07a550170a494381b5851af55608d9,

title = "Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial",

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.",

keywords = "Curcumin, Curcuminoids, FOLFOX chemotherapy, Metastatic colorectal cancer, Randomized controlled",

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

year = "2019",

month = jul,

day = "1",

doi = "10.1093/jn/nxz029",

language = "English",

volume = "149",

pages = "1133--1139",

journal = "Journal of Nutrition",

issn = "0022-3166",

publisher = "American Society for Nutrition",

number = "7",

}

Howells, LM, Iwuji, COO, Irving, GRB, Barber, S, Walter, H, Sidat, Z, Griffin-Teall, N, Singh, R, Foreman, N, Patel, SR, Morgan, B, Steward, WP, Gescher, A, Thomas, AL & Brown, K 2019, 'Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial', Journal of Nutrition, vol. 149, no. 7, pp. 1133-1139. https://doi.org/10.1093/jn/nxz029

TY - JOUR

T1 - Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial

AU - Howells, Lynne M.

AU - Iwuji, Chinenye O.O.

AU - Irving, Glen R.B.

AU - Barber, Shaun

AU - Walter, Harriet

AU - Sidat, Zahirah

AU - Griffin-Teall, Nicola

AU - Singh, Rajinder

AU - Foreman, Nalini

AU - Patel, Samita R.

AU - Morgan, Bruno

AU - Steward, William P.

AU - Gescher, Andreas

AU - Thomas, Anne L.

AU - Brown, Karen

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - Curcumin

KW - Curcuminoids

KW - FOLFOX chemotherapy

KW - Metastatic colorectal cancer

KW - Randomized controlled

UR - http://www.scopus.com/inward/record.url?scp=85069266743&partnerID=8YFLogxK

U2 - 10.1093/jn/nxz029

DO - 10.1093/jn/nxz029

M3 - Article

C2 - 31132111

AN - SCOPUS:85069266743

SN - 0022-3166

VL - 149

SP - 1133

EP - 1139

JO - Journal of Nutrition

JF - Journal of Nutrition

IS - 7

ER -

Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial

Abstract

Keywords

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