Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Clinical Trial

Effect of Nano-Curcumin on Radiotherapy-Induced Skin Reaction in Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled Trial

Author(s): Tamara Talakesh, Nasibeh Tabatabaee, Fatemeh Atoof, Akbar Aliasgharzadeh, Mostafa Sarvizade, Bagher Farhood* and Masoud Najafi*

Volume 15, Issue 4, 2022

Published on: 20 August, 2022

Page: [332 - 340] Pages: 9

DOI: 10.2174/1874471015666220623104316

Price: $65

Abstract

Purpose: Despite advances in medical technology, radiation-induced dermatitis occurs in 95% of cancer patients receiving radiation therapy. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The aim of this study was to determine the efficacy of nano-curcumin in alleviating the radiation-induced skin reactions (RISRs) in breast cancer patients.

Methods: A randomized, triple-blinded, placebo-controlled clinical trial was performed on 42 patients with breast cancer. The patients were randomly allocated to receive radiotherapy plus placebo (control group) and radiotherapy plus 80 mg/day nano-curcumin capsules (treatment group) up to two weeks after the end of treatment. Then, the RISRs (graded by the radiation therapy oncology group (RTOG) scale) and pain level of the patients were evaluated at baseline and weekly. Finally, the results were analyzed by T-test and Pearson chi-square test.

Results: According to the RTOG scale, 0%, 14.28%, and 85.71% of patients in the control group showed grades 0, 1, and 2 RISRs, respectively. In the treatment group, it was observed that 9.52%, 47.61%, and 42.85% of patients had grades 0, 1, and 2 RISRs, respectively. Compared to the control group, it was found that concomitant use of the nano-curcumin supplement did not significantly reduce the RISR severity during the first to sixth weeks (P > 0.05); however, there was a significant difference at week 7 (P = 0.01). Moreover, the patient-reported pain, as the secondary endpoint, was significantly reduced in the treatment group compared with the control group (P < 0.05).

Conclusions: In general, it was found that the administration of nano-curcumin could alleviate radiation- induced skin toxicity of breast cancer patients, but this effect was not significant.

Keywords: Breast cancer, radiation therapy, radiation-induced skin reaction, nano-curcumin, clinical trial, RTOG scale.

Graphical Abstract

[1]
Farhood, B.; Geraily, G.; Alizadeh, A. Incidence and mortality of various cancers in Iran and compare to other countries: a review article. Iran. J. Public Health, 2018, 47(3), 309-316.
[PMID: 29845017]
[2]
Mortezaee, K.; Ahmadi, A.; Haghi-Aminjan, H.; Khanlarkhani, N.; Salehi, E.; Shabani, N.M.; Farhood, B.; Najafi, M.; Sahebkar, A. Thyroid function following breast cancer chemotherapy: A systematic review. J. Cell. Biochem., 2019, 120(8), 12101-12107.
[http://dx.doi.org/10.1002/jcb.28771] [PMID: 31021464]
[3]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[4]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[5]
Bagheri, H.; Rabie Mahdavi, S.; Shekarchi, B.; Manouchehri, F.; Farhood, B. Measurement of the contralateral breast photon and thermal neutron doses in breast cancer radiotherapy: A comparison between physical and dynamic wedges. Radiat. Prot. Dosimetry, 2018, 178(1), 73-81.
[http://dx.doi.org/10.1093/rpd/ncx076] [PMID: 28591863]
[6]
Castaneda, S.A.; Strasser, J. Updates in the treatment of breast cancer with radiotherapy. Sur Oncol Clin, 2017, 26(3), 371-382.
[http://dx.doi.org/10.1016/j.soc.2017.01.013] [PMID: 28576177]
[7]
Fisher, B.; Anderson, S.; Bryant, J.; Margolese, R.G.; Deutsch, M.; Fisher, E.R.; Jeong, J-H.; Wolmark, N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N. Engl. J. Med., 2002, 347(16), 1233-1241.
[http://dx.doi.org/10.1056/NEJMoa022152] [PMID: 12393820]
[8]
Veronesi, U.; Cascinelli, N.; Mariani, L.; Greco, M.; Saccozzi, R.; Luini, A.; Aguilar, M.; Marubini, E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N. Engl. J. Med., 2002, 347(16), 1227-1232.
[http://dx.doi.org/10.1056/NEJMoa020989] [PMID: 12393819]
[9]
Santiago, R.J.; Wu, L.; Harris, E.; Fox, K.; Schultz, D.; Glick, J.; Solin, L.J. Fifteen-year results of breast-conserving surgery and definitive irradiation for stage I and II breast carcinoma: The University of Pennsylvania experience. Int J Rad Oncol, 2004, 58(1), 233-240.
[10]
Darby, S.; McGale, P.; Correa, C.; Taylor, C.; Arriagada, R.; Clarke, M.; Cutter, D.; Davies, C.; Ewertz, M.; Godwin, J.; Gray, R.; Pierce, L.; Whelan, T.; Wang, Y.; Peto, R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet, 2011, 378(9804), 1707-1716.
[http://dx.doi.org/10.1016/S0140-6736(11)61629-2] [PMID: 22019144]
[11]
Mahdavi, S.R.; Tutuni, M.; Farhood, B.; Nafisi, N.; Ghasemi, S.; Mirzaee, H.; Ahmadi, S.; Alizadeh, A. Measurement of peripheral dose to the pelvic region and the associated risk for cancer development after breast intraoperative electron radiation therapy. J. Radiol. Prot., 2019, 39(1), 278-291.
[http://dx.doi.org/10.1088/1361-6498/aafdc8] [PMID: 30634170]
[12]
Farhood, B.; Mahdavi, S.R.; Emranpour, M.H.; Mohammadi Asl, K.; Nekoui, N.; Knaup, C. Skin reaction in radiation therapy for breast cancer. Iran J Medical Phys, 2014, 11(4), 316-321.
[13]
Brady, L.W.; Perez, C.A. Perez & Brady’s principles and practice of radiation oncology; Lippincott Williams & Wilkins, 2013.
[14]
Kinoshita, K.; Ishimine, H.; Shiraishi, K.; Kato, H.; Doi, K.; Kuno, S.; Kanayama, K.; Mineda, K.; Mashiko, T.; Feng, J.; Nakagawa, K.; Kurisaki, A.; Itami, S.; Yoshimura, K. Cell and tissue damage after skin exposure to ionizing radiation: Short-and long-term effects after a single and fractional doses. Cells Tissues Organs, 2014, 200(3-4), 240-252.
[http://dx.doi.org/10.1159/000435809] [PMID: 26359658]
[15]
Naylor, W.; Mallett, J. Management of acute radiotherapy induced skin reactions: A literature review. Eur. J. Oncol. Nurs., 2001, 5(4), 221-233.
[http://dx.doi.org/10.1054/ejon.2001.0145] [PMID: 12849619]
[16]
Ryan Wolf, J.; Heckler, C.E.; Guido, J.J.; Peoples, A.R.; Gewandter, J.S.; Ling, M.; Vinciguerra, V.P.; Anderson, T.; Evans, L.; Wade, J.; Pentland, A.P.; Morrow, G.R. Oral curcumin for radiation dermatitis: A URCC NCORP study of 686 breast cancer patients. Support. Care Cancer, 2018, 26(5), 1543-1552.
[http://dx.doi.org/10.1007/s00520-017-3957-4] [PMID: 29192329]
[17]
Noble-Adams, R. Radiation-induced reactions. 1: An examination of the phenomenon. Br. J. Nurs., 1999, 8(17), 1134-1140.
[http://dx.doi.org/10.12968/bjon.1999.8.17.6503] [PMID: 10897695]
[18]
Julie Ryan, W.; Angela, M.H. radiation dermatitis; Available from: https://www.uptodate.com/contents/radiation-dermatitis#H3015184197
[19]
Chan, R.J.; Webster, J.; Chung, B.; Marquart, L.; Ahmed, M.; Garantziotis, S. Prevention and treatment of acute radiation-induced skin reactions: A systematic review and meta-analysis of randomized controlled trials. BMC Cancer, 2014, 14(1), 53.
[http://dx.doi.org/10.1186/1471-2407-14-53] [PMID: 24484999]
[20]
Maddocks-Jennings, W.; Wilkinson, J.M.; Shillington, D. Novel approaches to radiotherapy-induced skin reactions: A literature review. Complement. Ther. Clin. Pract., 2005, 11(4), 224-231.
[http://dx.doi.org/10.1016/j.ctcp.2005.02.001] [PMID: 16290892]
[21]
Huang, C.J.; Hou, M.F.; Kan, J.Y.; Juan, C.H.; Yuan, S.S.F.; Luo, K.H.; Chuang, H.Y.; Hu, S.C.S. Prophylactic treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis: A prospective, randomized, double-blind study. Evidence-Based Complementary and Alternative Medicine, 2015.
[http://dx.doi.org/10.1155/2015/312072]
[22]
Qi, F.; Li, A.; Inagaki, Y.; Gao, J.; Li, J.; Kokudo, N.; Li, X.K.; Tang, W. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer. Biosci. Trends, 2010, 4(6), 297-307.
[PMID: 21248427]
[23]
Moslemi, D.; Nokhandani, A.M.; Otaghsaraei, M.T.; Moghadamnia, Y.; Kazemi, S.; Moghadamnia, A.A. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature. Radiother. Oncol., 2016, 120(1), 13-20.
[http://dx.doi.org/10.1016/j.radonc.2016.04.001] [PMID: 27113797]
[24]
Chattopadhyay, I.; Biswas, K.; Bandyopadhyay, U.; Banerjee, R.K. Turmeric and curcumin: Biological actions and medicinal applications. Cur. Sci. Bangalore, 2004, 87(1), 44-53.
[25]
Maheshwari, R.K.; Singh, A.K.; Gaddipati, J.; Srimal, R.C. Multiple biological activities of curcumin: A short review. Life Sci., 2006, 78(18), 2081-2087.
[http://dx.doi.org/10.1016/j.lfs.2005.12.007] [PMID: 16413584]
[26]
Moutabian, H.; Ghahramani-Asl, R.; Mortezazadeh, T.; Laripour, R.; Narmani, A.; Zamani, H.; Ataei, G.; Bagheri, H.; Farhood, B.; Sathyapalan, T.; Sahebkar, A. The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: A systematic review. Biofactors, 2022, 48(3), 597-610.
[http://dx.doi.org/10.1002/biof.1823] [PMID: 35080781]
[27]
Zhang, Q.; Wu, L. In vitro and in vivo cardioprotective effects of curcumin against doxorubicin-induced cardiotoxicity: A Systematic Review. J. Oncol., 2022, 2022, 7277562.
[http://dx.doi.org/10.1155/2022/7277562] [PMID: 35237323]
[28]
Modaresi, M. HarfBol, M.; Ahmadi, F. A review on pharmacological effects and therapeutic properties of curcumin. Faslnamah-i Giyahan-i Daruyi, 2017, 2(62), 1-17.
[29]
Ono, K.; Hasegawa, K.; Naiki, H.; Yamada, M. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s β-amyloid fibrils in vitro. J. Neurosci. Res., 2004, 75(6), 742-750.
[http://dx.doi.org/10.1002/jnr.20025] [PMID: 14994335]
[30]
Ammon, H.; Anazodo, M. Curcumin: A potent inhibitor of leukotriene B4 formation in rat peritoneal polymorphonuclear neutrophils (PMNL). Planta Med., 58, 226.
[31]
Najafi, M.; Mortezaee, K.; Rahimifard, M.; Farhood, B.; Haghi-Aminjan, H. The role of curcumin/curcuminoids during gastric cancer chemotherapy: A systematic review of non-clinical study. Life Sci., 2020, 257, 118051.
[http://dx.doi.org/10.1016/j.lfs.2020.118051] [PMID: 32634426]
[32]
Mortezaee, K.; Salehi, E.; Mirtavoos-Mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol., 2019, 234(8), 12537-12550.
[http://dx.doi.org/10.1002/jcp.28122] [PMID: 30623450]
[33]
Farhood, B.; Mortezaee, K.; Goradel, N.H.; Khanlarkhani, N.; Salehi, E.; Nashtaei, M.S.; Najafi, M.; Sahebkar, A. Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy. J. Cell. Physiol., 2019, 234(5), 5728-5740.
[http://dx.doi.org/10.1002/jcp.27442] [PMID: 30317564]
[34]
Tejada, S.; Manayi, A.; Daglia, M.; Nabavi, S.F.; Sureda, A.; Hajheydari, Z.; Gortzi, O.; Pazoki-Toroudi, H.; Nabavi, S.M. Wound healing effects of curcumin: A short review. Curr. Pharm. Biotechnol., 2016, 17(11), 1002-1007.
[http://dx.doi.org/10.2174/1389201017666160721123109] [PMID: 27640646]
[35]
Barchitta, M.; Maugeri, A.; Favara, G.; Magnano San Lio, R.; Evola, G.; Agodi, A.; Basile, G. Nutrition and wound healing: An overview focusing on the beneficial effects of curcumin. Int. J. Mol. Sci., 2019, 20(5), 1119.
[http://dx.doi.org/10.3390/ijms20051119] [PMID: 30841550]
[36]
Akbik, D.; Ghadiri, M.; Chrzanowski, W.; Rohanizadeh, R. Curcumin as a wound healing agent. Life Sci., 2014, 116(1), 1-7.
[http://dx.doi.org/10.1016/j.lfs.2014.08.016] [PMID: 25200875]
[37]
Mitic, A.; Todorovic, K.; Stojiljkovic, N.; Stojanovic, N.; Ilic, S.; Todorovic, A.; Stojnev, S. Beneficial effects of curcumin on the wound-healing process after tooth extraction. Nat. Prod. Commun., 2017, 12(12), 1905-1908.
[http://dx.doi.org/10.1177/1934578X1701201223]
[38]
Kulac, M.; Aktas, C.; Tulubas, F.; Uygur, R.; Kanter, M.; Erboga, M.; Ceber, M.; Topcu, B.; Ozen, O.A. The effects of topical treatment with curcumin on burn wound healing in rats. J. Mol. Histol., 2013, 44(1), 83-90.
[http://dx.doi.org/10.1007/s10735-012-9452-9] [PMID: 23054142]
[39]
Falconieri, M.C.; Adamo, M.; Monasterolo, C.; Bergonzi, M.C.; Coronnello, M.; Bilia, A.R. New dendrimer-based nanoparticles enhance curcumin solubility. Planta Med., 2017, 83(5), 420-425.
[PMID: 27002394]
[40]
Li, M.; Xin, M.; Guo, C.; Lin, G.; Wu, X. New nanomicelle curcumin formulation for ocular delivery: Improved stability, solubility, and ocular anti-inflammatory treatment. Drug Dev. Ind. Pharm., 2017, 43(11), 1846-1857.
[http://dx.doi.org/10.1080/03639045.2017.1349787] [PMID: 28665151]
[41]
Fitzpatrick, T.B. The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol., 1988, 124(6), 869-871.
[http://dx.doi.org/10.1001/archderm.1988.01670060015008] [PMID: 3377516]
[42]
Wong, S.; Kaur, A.; Back, M.; Lee, K.M.; Baggarley, S.; Lu, J.J. An ultrasonographic evaluation of skin thickness in breast cancer patients after postmastectomy radiation therapy. Radiat. Oncol., 2011, 6(1), 9.
[http://dx.doi.org/10.1186/1748-717X-6-9] [PMID: 21261940]
[43]
Dugashvili, G.; Van den Berghe, L.; Menabde, G.; Janelidze, M.; Marks, L. Use of the universal pain assessment tool for evaluating pain associated with TMD in youngsters with an intellectual disability. Med. Oral Patol. Oral Cir. Bucal, 2017, 22(1), e88-e94.
[PMID: 27918746]
[44]
Ryan, J.L.; Heckler, C.E.; Ling, M.; Katz, A.; Williams, J.P.; Pentland, A.P.; Morrow, G.R. Curcumin for radiation dermatitis: A randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat. Res., 2013, 180(1), 34-43.
[http://dx.doi.org/10.1667/RR3255.1] [PMID: 23745991]
[45]
Sidhu, G.S.; Mani, H.; Gaddipati, J.P.; Singh, A.K.; Seth, P.; Banaudha, K.K.; Patnaik, G.K.; Maheshwari, R.K. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair Regen., 1999, 7(5), 362-374.
[http://dx.doi.org/10.1046/j.1524-475X.1999.00362.x] [PMID: 10564565]
[46]
Mohanty, C.; Sahoo, S.K. Curcumin and its topical formulations for wound healing applications. Drug Discov. Today, 2017, 22(10), 1582-1592.
[http://dx.doi.org/10.1016/j.drudis.2017.07.001] [PMID: 28711364]
[47]
Hussain, Z.; Thu, H.E.; Ng, S.F.; Khan, S.; Katas, H. Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art. Colloids Surf. B Biointerfaces, 2017, 150, 223-241.
[http://dx.doi.org/10.1016/j.colsurfb.2016.11.036] [PMID: 27918967]
[48]
Shaikh, J.; Ankola, D.D.; Beniwal, V.; Singh, D.; Kumar, M.N. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur. J. Pharm. Sci., 2009, 37(3-4), 223-230.
[http://dx.doi.org/10.1016/j.ejps.2009.02.019] [PMID: 19491009]
[49]
Shahani, K.; Swaminathan, S.K.; Freeman, D.; Blum, A.; Ma, L.; Panyam, J. Injectable sustained release microparticles of curcumin: A new concept for cancer chemoprevention. Cancer Res., 2010, 70(11), 4443-4452.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-4362] [PMID: 20460537]
[50]
Thangapazham, R.L.; Puri, A.; Tele, S.; Blumenthal, R.; Maheshwari, R.K. Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells. Int. J. Oncol., 2008, 32(5), 1119-1123.
[http://dx.doi.org/10.3892/ijo.32.5.1119] [PMID: 18425340]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy