Topical henna and curcumin (Alpha®) ointment efficacy for prevention of capecitabine induced hand-foot syndrome: A randomized, triple-blinded, placebo-controlled clinical

Sepideh Elyasi, Sara Rasta, Ali Taghizadeh-Kermani, Sare Hosseini, Sepideh Elyasi, Sara Rasta, Ali Taghizadeh-Kermani, Sare Hosseini

Abstract

Purpose: In this clinical trial, we evaluated Alpha® ointment efficacy in prevention of capecitabine induced hand-foot syndrome (HFS) in patients with gastrointestinal or breast cancers, for the first time.

Methods: During this pilot, randomized, triple-blinded, placebo-controlled clinical trial, the effect of Alpha® ointment (Lawsonia inermis 3 g and Curcuma longa 0.15 g/ 30 g) was assessed. It was applied on the palms and the soles, two times daily starting at the first day of chemotherapy for 4 consecutive courses. The severity of HFS was assessed at the end of the chemotherapy courses based on World Health Organization (WHO) scale and scored between 0-4.

Results: Ninety eligible patients were included randomly in the treatment or placebo group. Median WHO HFS grade was not significantly different between the two groups, during the follow-up period (P > 0.05). In the weekly assessment, the scores increased meaningfully in both the placebo and treatment groups, but there was a delay in HFS occurrence and deterioration in Alpha ointment group based on post hoc analysis.

Conclusion: Administration of Alpha® ointment containing henna and curcumin could not significantly prevent capecitabine induced HFS during 4 courses of treatment, but can somewhat delay its occurrence in patients with gastrointestinal or breast cancer.

Keywords: Hand-foot syndrome- Capecitabine- Henna- Lawsonia inermis- Curcumin.

Conflict of interest statement

Nothing to declare.

© 2022. Springer Nature Switzerland AG.

Figures

Fig. 1
Fig. 1
Flow diagram of the study design

References

    1. Sung H, Feraly J, Siegel RL, Laversanne M, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660.
    1. Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2019;33(2):379–386. doi: 10.1002/ptr.6231.
    1. Murugan K, Ostwal V, Carvalho MD, et al. Self-identification and management of hand–foot syndrome (HFS): effect of a structured teaching program on patients receiving capecitabine-based chemotherapy for colon cancer. Support Care Cancer. 2016;24(6):2575–2581. doi: 10.1007/s00520-015-3061-6.
    1. Elyasi S, Shojaee FSR, Allahyari A, Karimi G. Topical silymarin administration for prevention of capecitabine-induced hand–foot syndrome: A randomized, double-blinded, placebo controlled clinical trial. Phytother Res. 2017;31(9):1323–1329. doi: 10.1002/ptr.5857.
    1. Vodenkova S, Buchler T, Cervena K, Veskrnova V, et al. 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. Pharmacol Ther. 2020;206:107447. doi: 10.1016/j.pharmthera.2019.107447.
    1. Walko CM, Lindley C. Capecitabine: a review. Clin Ther. 2005;27(1):23–44. doi: 10.1016/j.clinthera.
    1. Baan J, Bos MM, Gonesh-Kisoensingh E, et al. Capecitabine induced toxicity: an outcome study into drug safety. J Integr Oncol. 2014;3(1):113. doi: 10.4172/2329-6771.1000113.
    1. Chalermchai T, Tantiphlachiva K, Suwanrusme H, Voravud N, Sriuranpong V. Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar–plantar erythrodysesthesia. Asia Pac J Clin Oncol. 2010;6(3):155–160. doi: 10.1111/j.1743-7563.2010.01311.x.
    1. Azuma Y, Hata K, Sai K, et al. Significant association between hand–foot syndrome and efficacy of capecitabine in patients with metastatic breast cancer. Biol Pharm Bull. 2012;35(5):717–724. doi: 10.1248/bpb.35.717.
    1. Chen M, Zhang L, Wang Q, Shen J. Pyridoxine for prevention of hand–foot syndrome caused by chemotherapy: a systematic review. PLoS ONE. 2013;8(8):e72245. doi: 10.1371/journal.pone.0072245.
    1. Common Terminology Criteria for Adverse Events V5.0 (CTCAE) (2017) Available from , (Accessed on March 20, 2021). Last updated 2017.
    1. Miller KK, Gorcey L, McLellan BN. Chemotherapy-induced hand–foot syndrome and nail changes: a review of clinical presentation, etiology, pathogenesis, and management. J Am Acad Dermatol. 2014;71:787–794. doi: 10.1016/j.jaad.2014.03.019.
    1. Asgari MM, Haggerty JG, McNiff JM, Milstone LM, Schwartz PM. Expression and localization of thymidine phosphorylase/platelet-derived endothelial cell growth factor in skin and cutaneous tumors. J Cutan Pathol. 1999;26(6):287–294. doi: 10.1111/j.1600-0560.1999.tb01846.x.
    1. Ilyas S, Wasif K, Saif MW. Topical henna ameliorated capecitabine-induced hand–foot syndrome. Cutan Ocul Toxicol. 2014;33(3):253–255. doi: 10.3109/15569527.2013.832280.
    1. Lassere Y, Hoff P. Management of hand–foot syndrome in patients treated with capecitabine (Xeloda) Eur J Oncol Nurs. 2004;8:31–40. doi: 10.1016/j.ejon.2004.06.007.
    1. Kandil HH, al-Ghanem MM, Sarwat MA, al-Thallab FS, Henna (Lawsonia inermis Linn.) inducing haemolysis among G6PD-deficient newborns. A new clinical observation. Ann Trop Paediatr. 1996;16:287–291. doi: 10.1080/02724936.1996.11747840.
    1. Mikhaeil BR, Badria FA, Maatooq GT, Amer MM. Antioxidant and immunomodulatory constituents of henna leaves. Z Naturforsch. 2004;59:468–476. doi: 10.1515/znc-2004-7-803.
    1. Yucel I, Guzin G. Topical henna for capecitabine induced hand–foot syndrome. Invest New Drugs. 2008;26(2):189–192. doi: 10.1007/s10637-007-9082-3.
    1. Nayak BS, Isitor G, Davis EM, Pillai GK. The evidence based wound healing activity of Lawsonia inermis Linn. Phytother Res. 2007;21:827–831. doi: 10.1002/ptr.2181.
    1. Philip Jacob P, Madhumitha G, Mary Saral A. Free radical scavenging and reducing power of Lawsonia inermis L. seeds. Asian Pac J Trop Med. 2011;4:457–461. doi: 10.1016/S1995-7645(11)60125-9.
    1. Akbari S, Kariznavi E, Jannati M, Elyasi S, Tayarani-Najaran Z. Curcumin as a preventive or therapeutic measure for chemotherapy and radiotherapy induced adverse reaction: A comprehensive review. Food Chem Toxicol. 2020;145:111699. doi: 10.1016/j.fct.2020.111699.
    1. Scontre VA, Martins JC, de Melo Sette CV, et al. Curcuma longa (turmeric) for prevention of capecitabine-induced hand-foot syndrome: a pilot study. J Diet Suppl. 2018;15(5):606–612. doi: 10.1080/19390211.2017.1366387.
    1. Gressett SM, Stanford BL, Hardwicke F. Management of hand–foot syndrome induced by capecitabine. J Oncol Pharm Pract. 2006;12(3):131–141. doi: 10.4081/oncol.2020.442.
    1. Nagore E, Insa A, Sanmartin O. Antineoplastic therapy induced palmar plantar erythrodysesthesia (‘hand–foot’) syndrome: incidence, recognition and management. Am J Clin Dermatol. 2000;1:225–234. doi: 10.2165/00128071-200001040-00004.
    1. Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016;25(3):1057–1073. doi: 10.1177/0962280215588241.
    1. Nikolaou V, Syrigos K, Saif MW. Incidence and implications of chemotherapy related hand–foot syndrome. Expert Opin Drug Saf. 2016;15(12):1625–1633. doi: 10.1080/14740338.2016.1238067.
    1. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352(11):1092–1102. doi: 10.1056/NEJMoa050493.
    1. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352(11):1081–1091. doi: 10.1056/NEJMoa050330.
    1. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352(11):1071–1080. doi: 10.1056/NEJMoa050405.
    1. Vakalis D, Ioannides D, Lazaridou E, Mattheou-Vakali G, Teknetzis A. Acral erythema induced by chemotherapy with cisplatin. Br J Dermatol. 1998;139(4):750–751. doi: 10.1046/j.1365-2133.1998.02487.x.
    1. Yamamoto D, Yamamoto C, Tanaka K. Novel and effective management of capecitabine induced hand foot syndrome. J Clin Oncol. 2008;26:2214–2215. doi: 10.1001/jamaoncol.2017.1269.
    1. Becker-Schiebe M, Mengs U, Schaefer M, Bulitta M, Hoffmann W. Topical use of a silymarin-based preparation to prevent radiodermatitis. Strahlenther Onkol. 2011;187(8):485–491. doi: 10.1007/s00066-011-2204-z.
    1. Ansari M, Farzin D, Mosalaei A, Omidvari S, et al. Efficacy of Topical Alpha Ointment (Containing Natural Henna) Compared to Topical Hydrocortisone (1%) in the Healing of Radiation-Induced Dermatitis in Patients with Breast Cancer: A Randomized Controlled Clinical Trial. Iran J Med Sci. 2013;38(4):293–300.
    1. Guha G, Rajkumar V, Kumar RA, Mathew L. Antioxidant Activity of Lawsonia inermis Extracts Inhibits Chromium(VI)-Induced Cellular and DNA Toxicity. Evid Based Complement Alternat Med. 2011;2011:576456. doi: 10.1093/ecam/nep205.
    1. Golmakani N, Rabiei Motlagh E, Tara F, Assili J, Shakeri MT. The Effects of Turmeric (Curcuma Longa L) Ointment on Healing of Episiotomy Site in Primiparous Women. J Obstet Gynecol Infertil. 2008;11(4):29–39. doi: 10.22038/IJOGI.2008.5909.
    1. Cheppudira B, Fowler M, McGhee L, Greer A, Mares A, Petz L, et al. Curcumin: a novel therapeutic for burn pain and wound healing. Expert Opin Investig Drugs. 2013;22(10):1295–1303. doi: 10.1517/13543784.2013.825249.
    1. Habbal OA, Al-Jabri AA, El-Hag AH, Al-Mahrooqi ZH, Al-Hashmi NA (2005) In-vitro antimicrobial activity of Lawsonia inermis Linn (henna). A pilot study on the Omani henna. Saudi Med J. 26(1):69e72. PMID: 15756356.
    1. Hosseini SV, Tanideh N, Kohanteb J, Ghodrati Z, et al. Comparison between Alpha and silver sulfadiazine ointments in treatment of Pseudomonas infections in 3rd degree burns. Int J Surg. 2007;5(1):23–26. doi: 10.1016/j.ijsu.2006.03.007.
    1. Puri N, Puri A. A study on contact dermatitis to hair dye and henna. Our Dermatol. 2013;4(4):545–548. doi: 10.7241/ourd.20134.137.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa