Evaluation of Nano-curcumin Oral Formulation Efficacy as an Adjuvant Treatment in Metastatic Colorectal Patients
-
Mahdi Jannati Yazdan Abad
,
Abolghasem Allahyari
,
Mostafa Kamandi
,
Omid Araste
,
Mehdi Varmaghani
,
Hedyieh Karbasforooshan
,
Mahmoud Reza Jaafari
,
Sepideh Elyasi
Abstract
Backgrounds: Globally, colorectal cancer ranks as the second cause of mortality and the third most diagnosed cancer. Curcumin has been investigated as an adjunct therapy in various cancers, mostly in pre-clinical studies, particularly by acting as a chemo-sensitizer.
Objectives: The present study aimed to evaluate the effectiveness of oral formulation of nano-curcumin as an adjuvant treatment in patients with metastatic colorectal cancer receiving the XELOX/FOLFOX±Bevacizumab regimen.
Methods: In this study, 94 patients with metastatic colorectal cancer who completed the inclusion and exclusion criteria were randomized into the nano-curcumin and placebo groups. 40 mg nano-curcumin capsules were administered three times a day after each meal, beginning the first day to the end of the sixth cycle of chemotherapy. Carcinoembryonic antigen (CEA) level and radiological response based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) were evaluated. The data were analyzed using SPSS version 13.
Results: All baseline demographic, clinical, and laboratory variables were comparable between placebo and nano-curcumin groups. The administration of nano-curcumin showed no significant impact on carcinoembryonic antigen (CEA) levels. There was also no significant difference in both arms regarding RECIST criteria at the end of the 3rd and 6th cycle.
Conclusion: Our findings suggest that nano-curcumin with the prescribed dose did not show considerable efficacy in the radiologic response of metastatic colorectal cancer based on RECIST criteria. The CEA serum level also did not change significantly in comparison with the placebo. Further research is needed to assess various nano-curcumin formulations, dosing, and timing for initiating curcumin for better judgment.
Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al. Global Burden of Colorectal Cancer in 2020 and 2040: Incidence and Mortality Estimates from GLOBOCAN. Gut. 2023;72(2):338-44.
Stohs SJ, Chen O, Ray SD, Ji J, Bucci LR, Preuss HG. Highly Bioavailable forms of Curcumin and Promising Avenues for Curcumin-based Research and Application: a review. Molecules. 2020;25(6):1397.
Hossain MS, Karuniawati H, Jairoun AA, Urbi Z, Ooi DJ, John A, et al. Colorectal Cancer: A review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk factors, Preventive and Treatment Strategies. Cancers. 2022;14(7):1732.
Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325(7):669-685.
Xie YH, Chen YX, Fang JY. Comprehensive Review of Targeted Therapy for Colorectal Cancer. Signal Transduct Target Ther. 2020;5(1):22.
Kumar A, Gautam V, Sandhu A, Rawat K, Sharma A, Saha L. Current and Emerging Therapeutic Approaches for Colorectal Cancer: A Comprehensive Review. World J Gastrointest Surg. 2023 4;15(4):495.
Ohishi T, Kaneko MK, Yoshida Y, Takashima A, Kato Y, Kawada M. Current Targeted Therapy for Metastatic Colorectal Cancer. Int J Mol Sci. 2023;24(2):1702.
Salehifar E, Gheibi S, Janbabaei G, Mousavi K. Adverse Effects of Chemotherapy Regimens Used in Colorectal Cancer Patients in a Referral Cancer Center in North of Iran, 2008-2014. J Pharm Care. 2017;4(1-2):9-13.
Jeon Y, Sym SJ, Yoo BK, Baek JH. Long-term Survival, Tolerability, and Safety of First-line Bevacizumab and FOLFIRI in Combination with Ginsenoside-modified Nanostructured Lipid Carrier Containing Curcumin in Patients with Unresectable Metastatic Colorectal Cancer. Integr Cancer Ther. 2022;21:15347354221105498.
Kogan LG, Davis SL, Brooks GA. Treatment Delays During FOLFOX Chemotherapy in Patients with Colorectal Cancer: A Multicenter Retrospective Analysis. J Gastrointest Oncol. 2019;10(5):841-846.
Keramida K, Charalampopoulos G, Filippiadis D, Tsougos E, Farmakis D. Cardiovascular Complications of Metastatic Colorectal Cancer Treatment. J Gastrointest Oncol. 2019;10(4):797-806.
Farashi E, Mahmoodpour A, Movassaghpour Akbari A, Sanaat Z, Sarbakhsh P, Chavoshi SH, et al. An Investigation of Insulin Resistance and Cachexia Relation in Patients with Metastatic Gastrointestinal Malignancies. J Pharm Care. 2022;10(4):195-204.
- Cocetta V, Quagliariello V, Fiorica F, Berretta M, Montopoli M. Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives. Int J Mol Sci. 2021; 22(4):2049.
- Wei Y, Yang P, Cao S, Zhao L. The Combination of Curcumin and 5-fluorouracil in Cancer Therapy. Arch Pharm Res. 2018;41:1-3.
Gavrilas LI, Cruceriu D, Mocan A, Loghin F, Miere D, Balacescu O. Plant-derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-resistance. Biomedicines. 2022;10(8):1948.
Batra H, Pawar S, Bahl D. Curcumin in Combination With Anti-cancer Drugs: A Nanomedicine Review. Pharmacol Res. 2019;139: 91-105.
Ojo OA, Adeyemo TR, Rotimi D, Batiha GE, Mostafa-Hedeab G, Iyobhebhe ME, et al. Anticancer Properties of Curcumin Against Colorectal Cancer: A Review. Front Oncol. 2022;12:881641.
Tan BL, Norhaizan ME. Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer. Molecules. 2019;24(14):2527.
Edgar R. Miller, Roberto Pastor-Barriuso, Darshan Dalal, et al. Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Ann Intern Med. 2005;142(1):37-46.
Yasueda A, Urushima H, Ito T. Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review. Integr Cancer Ther. 2016;15(1):17-39.
Hejazi J, Rastmanesh R, Taleban FA, Molana SH, Ehtejab G. A Pilot Clinical Trial of Radioprotective Effects of Curcumin Supplementation in Patients with Prostate Cancer. J Cancer Sci Ther. 2013;5:320-324.
Ladas EJ, Jacobson JS, Kennedy DD, Teel K, Fleischauer A, Kelly KM. Antioxidants and Cancer Therapy: A Systematic Review. J Clin Oncol. 2004;22(3):517-528.
Rahimi HR, Jaafari MR, Mohammadpour AH, Abnous K, Ghayour Mobarhan M, Ramezanzadeh E, et al. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease. Asia Pac J Med Toxicol. 2015; 4(1):25-30.
Allen A, Flemstrom G, Garner A, Kivilaakso E. Gastroduodenal Mucosal Protection. Physiological reviews. 1993;73(4):823-857.
Rahimi HR, Kazemi Oskuee R. Curcumin from traditional Iranian medicine to molecular medicine. Razavi Int J Med. 2014;2(2):e19982.
1. Howles PN. Cholesterol Absorption and Metabolism. In: Proetzel G, Wiles MV, editors. Mouse Models for Drug Discovery: Methods and Protocols. Totowa, NJ: Humana Press; 2010. p. 157-79.
U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Internet]. Bethesda (MD): National Cancer Institute; 2017 Nov 27 [cited 2025 Feb 5]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf
Eisenhauer EA, Therasse P, Bogaerts J, et al. New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
Greil R, Greil-Ressler S, Weiss L, Schönlieb C, Magnes T, Radl B, et al. A phase 1 Dose-escalation Study on the Safety, Tolerability and Activity of Liposomal Curcumin (Lipocurc™) in Patients with Locally Advanced or Metastatic Cancer. Cancer Chemother Pharmacol. 2018;82:695-706.
Purbadi S, Rustamadji P, Prijanti AR, Sekarutami SM, Sutrisna B, Suyatna FD, et al. Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double‐Blind Randomised Placebo‐Controlled Trial. Evid Based Complement Alternat Med. 2020;2020(1):1986793.
Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, et al. Pharmacodynamic and Pharmacokinetic Study of Oral Curcuma Extract in Patients with Colorectal Cancer. Clin Cancer Res. 2001;7(7):1894-900.
Su YT, Chen JW, Chang SC, Jiang JK, Huang SC. The Clinical Experience of the Prognosis in Opposite CEA and Image Change After Therapy in Stage IV Colorectal Cancer. Sci Rep. 2022;12(1):20075.
Howells L, Malhotra Mukhtyar R, Theofanous D, Pepper C, Thomas A, Brown K, et al. Systematic Review Assessing Clinical Utility of Curcumin with a Focus on Cancer Prevention. Mol Nutr Food Res. 2021;65(13):2000977.
Ojo OA, Adeyemo TR, Rotimi D, et al. Anticancer Properties of Curcumin Against Colorectal Cancer: A Review. Front Oncol. 2022;12:881641.
Panknin TM, Howe CL, Hauer M, Bucchireddigari B, Rossi AM, Funk JL. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci. 2023;24(5):4476.
Mansouri K, Rasoulpoor S, Daneshkhah A, Abolfathi S, Salari N, Mohammadi M, et al. Clinical Effects of Curcumin in Enhancing Cancer Therapy: A Systematic Review. BMC cancer. 2020; 20(1):791.
Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, et al. A Phase I/II Study of Gemcitabine-based Chemotherapy Plus Curcumin for Patients with Gemcitabine-Resistant Pancreatic Cancer. Cancer Chemother Pharmacol. 2011;68:157-164.
Tabrizi R, Vakili S, Akbari M, Mirhosseini N, Lankarani KB, Rahimi M, et al. The Effects of Curcumin‐containing Supplements on Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta‐analysis of Randomized Controlled Trials. Phytother Res. 2019;33(2):253-262.
De Waure C, Bertola C, Baccarini G, Chiavarini M, Mancuso C. Exploring the Contribution of Curcumin to Cancer Therapy: A Systematic Review of Randomized Controlled Trials. Pharmaceutics. 2023;15(4):1275.
Gunther JR, Chadha AS, Guha S, Raju GS, Maru DM, Munsell MF, et al. A Phase II Randomized Double-Blinded Trial Evaluating the Efficacy of Curcumin with Pre-operative Chemoradiation for Rectal Cancer. J Gastrointest Oncol. 2022;13(6):2938.
Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, et al. Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and Their Pharmacodynamic Consequences. Cancer Epidemiol Biomarkers Prev. 2005;14(1):120-125.
| Files | ||
| Issue | Vol 13, No 1 (Winter 2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| FOLFOX/ XELOX ± Bevacizumab Nano-curcumin Chemotherapy Toxicity Cancer Progression Metastatic Colorectal Cancer | ||
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