EFFICACY AND SAFETY OF STANDARDIZED CINNAMON BARK EXTRACT FOR THE PREVENTION OF CHEMOTHERAPY-INDUCED WEIGHT LOSS AND ALOPECIA IN PATIENTS WITH BREAST CANCER: A RANDOMIZED, DOUBLE-BLIND, AND PLACEBO-CONTROLLED STUDY
Keywords:Cinnamon bark extract, Chemotherapy-induced alopecia, Weight loss, Side effects, Breast cancer patients
Objective: The objective of the study was to evaluate the effects of IND02 (standardized Cinnamon bark extract) supplementation for the prevention of side effects of cancer chemotherapy in female patients with breast cancer.
Methods: The study was conducted using double-blind, placebo-controlled design in 34 female breast cancer patients during the first 4 consecutive 21-day cycles of the standard chemotherapy regimen. The active treatment (IND02 capsules, 400 mg, one capsule, and thrice a day) or matching placebo was orally administrated in randomized (1:1 ratio) patients. The efficacy outcome measures were reduction in chemotherapy-induced weight loss, alopecia (hair fall), and other side effects. The safety outcome measures were hematology, ECG, vital signs, adverse event monitoring, and laboratory safety measurements.
Results: The patients on the treatment with IND02 had shown significant protection from chemotherapy-induced severe weight loss (cachexia) and alopecia (reduced hair density and % hairs in the anagen phase, and increased % hairs in telogen phase) which was seen in the placebo group. IND02 treatment was found safe and well-tolerated during the study.
Conclusion: Concomitant use of IND02 in breast cancer patients during breast cancer chemotherapy showed a clinical promise regarding efficacy and safety in preventing chemotherapy-induced weight loss and alopecia.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
Nithya T, Sumalatha D. Evaluation of in vitro anti-oxidant and anticancer activity of Coriandrum sativum against human colon cancer HT-29 cell lines. Int J Pharm Pharm Sci 2014;6:421-4.
Lyman GH. Oxford American Handbook of Oncology. New York: Oxford University Press; 2009.
Skeel RT, Khleif SN. Handbook of Cancer Chemotherapy. 8th ed. Philadelphia, PA: Wolter Kluwer; 2011.
Sak K. Chemotherapy and dietary phytochemical agents. Chemother Res Pract 2012;2012:282570.
Dixit S. Natural flavonoids: A novel approach to breast cancer (review). Innovare J Food Sci 2017;5:1-5.
Sharma V, Chaudhary U. An overview on indigenous knowledge of Achyranthes aspera. J Crit Rev 2015;2:7-19.
Rupeshkumar M, Kavitha K, Haldar PK. Role of herbal plants in the diabetes mellitus therapy: An overview. Int J Appl Pharm 2014;6:1-3.
Balijepalli MK, Buru AS, Sakirolla R, Pichika M. Cinnamomum genus: A review on its biological activities. Int J Pharm Pharm Sci 2017;9:1-11.
Gajalakshmi S, Vijayalakshmi S, Rajeswari VD. Phytochemical and pharmacological properties of Annona muricata: A review. Int J Pharm Pharm Sci 2012;4:3-6.
Warrier PK, Ramankutty C, Nambiar VP, Nair RV. Indian Medicinal Plants: A Compendium of 500 Species. Madras: Orient Longman; 1993.
Niphade SR, Asad M, Chandrakala GK, Toppo E, Deshmukh P. Immunomodulatory activity of Cinnamomum zeylanicum bark. Pharm Biol 2009;47:1168-73.
Pahan K. Immunomodulation of experimental allergic encephalomyelitis by cinnamon metabolite sodium benzoate. Immunopharmacol Immunotoxicol 2011;33:586-93.
Balekar N, Bodhankar SL, Mohan V, Thakurdesai PA. Modulatory activity of a polyphenolic fractions of Cinnamomum zeylanicum L. bark on multiple arms of immunity in normal and immunocompromised mice. J Appl Pharm Sci 2014;4:114-22.
Herdwiani W, Soemardji A, Elfahmi TM, Tan M. A review of cinnamon as a potent anticancer drug. Asian J Pharm Clin Res 2016;9:8-13.
Ghaffarie T, Johari H, Najafian M, Kargar H. Effect of hydroalcoholic extract of cinnamon on the pituitary-gonadal axis in adult male rats under chemotherapy by cyclophosphamide. Zahedan J Res Med Sci 2013;16:16-20.
Dudonné S, Vitrac X, Coutière P, Woillez M, Mérillon JM. Comparative study of antioxidant properties and total phenolic content of 30 plant extracts of industrial interest using DPPH, ABTS, FRAP, SOD, and ORAC assays. J Agric Food Chem 2009;57:1768-74.
Mathew S, Abraham TE. Studies on the antioxidant activities of cinnamon (Cinnamomum verum) bark extracts, through various in vitro models. Food Chem 2006;94:520-8.
Rathi B, Bodhankar S, Mohan V, Thakurdesai P. Ameliorative effects of a polyphenolic fraction of Cinnamomum zeylanicum L. Bark in animal models of inflammation and arthritis. Sci Pharm 2013;81:567-89.
Vetal S, Bodhankar SL, Mohan V, Thakurdesai PA. Anti-inflammatory and anti-arthritic activity of Type-A procyanidine polyphenols from bark of Cinnamomum zeylanicum in rats. Food Sci Hum Wellness 2013;2:59-67.
Kandhare A, Bodhankar SL, Singh V, Mohan V, Thakurdesai PA. Anti-asthmatic effects of Type-A procyanidine polyphenols from cinnamon bark in ovalbumin-induced airway hyperresponsiveness in laboratory animals. Biomed Aging Pathol 2013;3:23-30.
Walanj S, Walanj A, Mohan V, Thakurdesai PA. Efficacy and safety of intranasal cinnamon bark extract in seasonal allergic rhinitis patients: A double-blind placebo-controlled pilot study. J Herb Med 2014;4:37-47.
Kandhare A, Aswar U, Mohan V, Bodhankar SL, Thakudesai PA. Effect of Type-A Procyanidine Polyphenols from Bark of Cinnamomum zeylanicum on Allergic Rhinitis Model in Balb-c mice [GU-6]. 45th Annual Conference of Indian Pharmacological Society (IPSCON-2012) and International Conference on “Navigating Pharmacology towards Safe and Effective Therapy”. Nagpur: Indian Pharmacological Society; 2013. p. 318-9.
Kandhare A, Bodhankar SL, Mohan V, Thakudesai PA. Toxicological Evaluations of Type-A Procyanidine Polyphenols from Cinnamon Bark [OP-10]. XXXIII Annual Conference of Society of Toxicology (STOX), India for Synergy of Toxicology Research In SAARC Countries Mathura, India; 2013.
Martin M, Villar A, Sole-Calvo A, Gonzalez R, Massuti B, Lizon J, et al. Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: A study by the GEICAM group. Ann Oncol 2003;14:833-42.
Eilers J, Epstein JB. Assessment and measurement of oral mucositis. Semin Oncol Nurs 2004;20:22-9.
Wood LJ, Nail LM, Gilster A, Winters KA, Elsea CR. Cancer chemotherapy-related symptoms: Evidence to suggest a role for proinflammatory cytokines. Oncol Nurs Forum 2006;33:535-42.
Bauer JD, Capra S. Nutrition intervention improves outcomes in patients with cancer cachexia receiving chemotherapy – a pilot study. Support Care Cancer 2005;13:270-4.
Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 2011;480:480-9.
Criscitiello C, Esposito A, Gelao L, Fumagalli L, Locatelli M, Minchella I, et al. Immune approaches to the treatment of breast cancer, around the corner? Breast Cancer Res 2014;16:204.
Siu D. Natural products and their role in cancer therapy. Med Oncol 2011;28:888-900.
Nakamura K, Sasayama A, Takahashi T, Yamaji T. An immune-modulating diet in combination with chemotherapy prevents cancer cachexia by attenuating systemic inflammation in colon 26 tumor-bearing mice. Nutr Cancer 2015;67:912-20.
Wood LJ, Nail LM, Perrin NA, Elsea CR, Fischer A, Druker BJ, et al. The cancer chemotherapy drug etoposide (VP-16) induces proinflammatory cytokine production and sickness behavior-like symptoms in a mouse model of cancer chemotherapy-related symptoms. Biol Res Nurs 2006;8:157-69.
Pusztai L, Mendoza TR, Reuben JM, Martinez MM, Willey JS, Lara J, et al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 2004;25:94-102.
Cao H, Urban JF Jr., Anderson RA. Cinnamon polyphenol extract affects immune responses by regulating anti-and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr 2008;138:833-40.
Lee BJ, Kim YJ, Cho DH, Sohn NW, Kang H. Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation. Immunopharmacol Immunotoxicol 2011;33:714-22.
Hong JW, Yang GE, Kim YB, Eom SH, Lew JH, Kang H, et al. Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models. BMC Complement Altern Med 2012;12:237.
Harris J, Sengar D, Stewart T, Hyslop D. The effect of immunosuppressive chemotherapy on immune function in patients with malignant disease. Cancer 1976;37:1058-69.
Okamoto M, Kasetani H, Kaji R, Goda H, Ohe G, Yoshida H, et al. Cis-diamminedichloroplatinum and 5-fluorouracil are potent inducers of the cytokines and natural killer cell activity in vivo and in vitro. Cancer Immunol Immunother 1998;47:233-41.
Li LH, DeKoning TF, Wallace TL. Relationship between modulation of natural killer cell activity and antitumor activity of bropirimine when used in combination with various types of chemotherapeutic drugs. Cancer Res 1987;47:5894-900.
Hesketh PJ, Batchelor D, Golant M, Lyman GH, Rhodes N, Yardley D, et al. Chemotherapy-induced alopecia: Psychosocial impact and therapeutic approaches. Support Care Cancer 2004;12:543-9.
Tierney AJ, Taylor J, Closs SJ. Knowledge, expectations and experiences of patients receiving chemotherapy for breast cancer. Scand J Caring Sci 1992;6:75-80.
Lemieux J, Maunsell E, Provencher L. Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: A literature review. Psychooncology 2008;17:317-28.
Freedman TG. Social and cultural dimensions of hair loss in women treated for breast cancer. Cancer Nurs 1994;17:334-41.
van den Hurk CJ, Winstanley J, Young A, Boyle F. Measurement of chemotherapy-induced alopecia-time to change. Support Care Cancer 2015;23:1197-9.
Nakashima-Kamimura N, Nishimaki K, Mori T, Asoh S, Ohta S. Prevention of chemotherapy-induced alopecia by the anti-death FNK protein. Life Sci 2008;82:218-25.
Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH, et al. Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1. BMC Cancer 2010;10:392.
Kwon HK, Jeon WK, Hwang JS, Lee CG, So JS, Park JA, et al. Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells. Cancer Lett 2009;278:174-82.
Roy AM, Baliga MS, Elmets CA, Katiyar SK. Grape seed proanthocyanidins induce apoptosis through p53, bax, and caspase 3 pathways. Neoplasia 2005;7:24-36.
Mantena SK, Baliga MS, Katiyar SK. Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells. Carcinogenesis 2006;27:1682-91.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.