Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial.
Administration, Oral
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Curcumin
/ administration & dosage
Female
Fluorouracil
/ administration & dosage
Humans
Leucovorin
/ administration & dosage
Male
Middle Aged
Neoplasm Metastasis
Organoplatinum Compounds
/ administration & dosage
Treatment Outcome
FOLFOX chemotherapy
curcumin
curcuminoids
metastatic colorectal cancer
randomized controlled trial
Journal
The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
26
09
2018
revised:
19
11
2018
accepted:
06
02
2019
pubmed:
28
5
2019
medline:
9
4
2020
entrez:
28
5
2019
Statut:
ppublish
Résumé
Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anticancer properties. 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). 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31132111
pii: S0022-3166(22)16657-5
doi: 10.1093/jn/nxz029
pmc: PMC6602900
doi:
Substances chimiques
Organoplatinum Compounds
0
Curcumin
IT942ZTH98
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Banques de données
ClinicalTrials.gov
['NCT01490996']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1133-1139Subventions
Organisme : Cancer Research UK
ID : 13101
Pays : United Kingdom
Informations de copyright
Copyright © American Society for Nutrition 2019.
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