A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease.
Abstract: Equine sarcoids (ES) are the most common cutaneous tumors in equids. Systemic treatment options are sparse. Subcutaneous (SC) injections of Viscum album extract (VAE) demonstrate efficacy as a systemic treatment directed against ES. Objective: To critically assess the therapeutic efficacy of orally administered VAE. Methods: Forty-five ES-affected, privately owned, 3-12 year-old horses. Methods: A 3-armed randomized placebo-controlled, double-blinded study was conducted in a double-dummy design. Horses were subjected to oral administration and SC injections of either VAE or placebo (VAE oral/placebo SC, VAE SC/placebo oral, placebo oral/placebo SC) over a 7-month treatment period. Primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months. Second endpoint was the clinical response. Results: No statistically significant difference in the composite endpoint between the 3 study arms was found. The primary endpoint showed 4 (27%) horses in the VAE oral group with complete ES regression, 3 (21%) in the VAE SC injection group, and 2 (13%) in the placebo group. The clinical response revealed complete or partial regression in 6 horses of the oral VAE group (40%), 4 of the SC injection group (29%), and 4 of the placebo group (25%). Direct comparison of oral VAE and placebo showed an odds ratio, stratified for prognosis of 2.16 (95%-CI: 0.45-10.42) and a P-value of 0.336. Conclusions: Oral administration of VAE is well tolerated. No statistically significant difference in the effectiveness of systemic VAE versus placebo against ES was found.
© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2024-03-26 PubMed ID: 38529853DOI: 10.1111/jvim.17052Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research examined the effectiveness of orally administered Viscum album extract (VAE), a mistletoe extract, in treating equine sarcoids (ES), which are common skin tumours in horses. The study, which was a randomized, double-blinded, and placebo-controlled, did not find a statistically significant difference in the therapeutic efficacy of orally administered VAE compared to subcutaneous injections or a placebo.
Study Overview
- This investigation is a randomized, placebo-controlled, double-blinded study with a double-dummy design.
- The focus is on the treatment of Equine Sarcoids (ES), the most common skin tumors in horses.
- The treated groups were given Viscum Album Extract (VAE), a mistletoe extract, either orally or in a subcutaneous (SC) injection. The control group received a placebo treatment, either taken orally or as an SC injection.
Methods
- 45 horses aged between 3 and 12 who were privately owned and affected by ES took part in the study.
- The horses were subjected to a 7-month treatment period where they received their assigned treatment type.
- The primary endpoint was the change of baseline of a composite index of ES number and ES area after 14 months.
- The secondary endpoint was the clinical response to the treatment.
Results
- No statistically significant difference was found between the three groups.
- Four horses (27%) in the VAE oral group, three (21%) in the VAE SC injection group, and two (13%) in the placebo group showed complete ES regression in the primary endpoint.
- In terms of clinical response, complete or partial regression was observed in six horses from the oral VAE group (40%), four from the SC injection group (29%), and four from the placebo group (25%).
Conclusions
- The oral administration of VAE was well tolerated by the horses.
- However, the study’s results do not show a statistically significant difference in the effectiveness of systemic VAE against ES, compared to a placebo.
Cite This Article
APA
Beermann A, Clottu O, Reif M, Biegel U, Unger L, Koch C.
(2024).
A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease.
J Vet Intern Med.
https://doi.org/10.1111/jvim.17052 Publication
Researcher Affiliations
- Research Institute of Organic Agriculture (FiBL), Department of Livestock Sciences, Frick, Switzerland.
- Research Institute of Organic Agriculture (FiBL), Department of Livestock Sciences, Frick, Switzerland.
- Society of Clinical Research e.V, Berlin, Germany.
- Research Institute of Organic Agriculture (FiBL), Department of Livestock Sciences, Frick, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), University of Bern, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), University of Bern, Bern, Switzerland.
Grant Funding
- The Society of Cancer Research, Arlesheim, Switzerland
- The Veterinary Association of the Canton of Neuchu00e2tel, Neuchu00e2tel, Switzerland
- The Swiss Veterinary Association for Alternative and Complementary Medicine (camvet.ch), Bern, Switzerland
- The Rudolf Steiner Fund for Scientific Research e.V., Nuremberg, Germany
References
This article includes 60 references
- Schaffer PA, Wobeser B, Martin LER, Dennis MM, Duncan CG. Cutaneous neoplastic lesions of equids in the central United States and Canada: 3,351 biopsy specimens from 3,272 equids (2000–2010). J Am Vet Med Assoc 2013;242(1):99–104.
- Knowles EJ, Tremaine WH, Pearson GR, Mair TS. A database survey of equine tumours in the United Kingdom. Equine Vet J 2016;48(3):280–284.
- Bergvall KE. Sarcoids. Vet Clin N Am Equine Pract 2013;29(3):657–671.
- Taylor S, Haldorson G. A review of equine sarcoid. Equine Vet Educ 2013;25(4):210–216.
- Marti E, Lazary S, Antczak DF, Gerber H. Report of the first international workshop on equine sarcoid*. Equine Vet J 1993;25(5):397–407.
- Martens A, De Moor A, Vlaminck L, Pile F, Steenhaut M. Evaluation of excision, cryosurgery and local BCG vaccination for the treatment of equine sarcoids. Vet Rec 2001;149(22):665–669.
- Lane JG. The treatment of equine Sarcoids by cryosurgery. Equine Vet J 1977;9(3):127–133.
- Carstanjen B, Jordan P, Lepage OM. Carbon dioxide laser as a surgical instrument for sarcoid therapy–a retrospective study on 60 cases. Can Vet J 1997;38(12):773–776.
- Théon AP, Pascoe JR. Iridium–192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses. Equine Vet J 1995;27(2):117–121.
- Byam-Cook KL, Henson FMD, Slater JD. Treatment of periocular and non–ocular sarcoids in 18 horses by interstitial brachytherapy with iridium–192. Vet Rec 2006;159(11):337–341.
- Hollis AR. Radiotherapy for the treatment of periocular tumours in the horse. Equine Vet Educ 2019;31(12):647–652.
- Théon AP, Pascoe JR, Carlson GP, Krag DN. Intratumoral chemotherapy with cisplatin in oily emulsion in horses. J Am Vet Med Assoc 1993;202(2):261–267.
- Théon AP, Pascoe JR, Galuppo LD, Fisher PE, Griffey SM, Madigan JE. Comparison of perioperative versus postoperative intratumoral administration of cisplatin for treatment of cutaneous sarcoids and squamous cell carcinomas in horses. J Am Vet Med Assoc 1999;215(11):1655–1660.
- Malalana F, Knottenbelt D, McKane S. Mitomycin C. With or without surgery, for the treatment of ocular squamous cell carcinoma in horses. Vet Rec 2010;167(10):373–376.
- Knottenbelt DC, Walker JA. Topical treatment of the equine sarcoid. Equine Vet Educ 1994;6(2):72–75.
- Stewart AA, Rush B, Davis E. The efficacy of intratumoural 5-fluorouracil for the treatment of equine sarcoids. Aust Vet J 2006;84(3):101–106.
- Knottenbelt DC, Watson AH, Hotchkiss JW, Chopra S, Higgins AJ. A pilot study on the use of ultra-deformable liposomes containing bleomycin in the treatment of equine sarcoid. Equine Vet Educ 2020;32(5):258–263.
- Fürst M, Auer JA. Klinische Studie Über Den Einsatz von Bleomycin Bei Der Behandlung von Equinen Sarkoiden. University of Zurich 2006.
- Vanselow BA, Abetz I, Jackson AR. BCG emulsion immunotherapy of equine sarcoid. Equine Vet J 1988;20(6):444–447.
- Nogueira SAF, Torres SMF, Malone ED, Diaz SF, Jessen C, Gilbert S. Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study. Vet Dermatol 2006;17(4):259–265.
- Haspeslagh M, Vlaminck LEM, Martens AM. Treatment of sarcoids in equids: 230 cases (2008-2013). J Am Vet Med Assoc 2016;249(3):311–318.
- Felbert I, Dreschel W, Teifke J. Regression of an equine sarcoid after treatment with a compound of Sanguinadd canadensis–a case report. Prakt Tierarzt 2005;86:330–334.
- Rothacker CC, Boyle AG, Levine DG. Autologous vaccination for the treatment of equine sarcoids: 18 cases (2009-2014). Can Vet J 2015;56(7):709–714.
- Kinnunen RE, Tallberg T, Stenbäck H, Sarna S. Equine sarcoid tumour treated by autogenous tumour vaccine. Anticancer Res 1999;19(4C):3367–3374.
- Christen-Clottu O, Klocke P, Burger D, Straub R, Gerber V. Treatment of clinically diagnosed equine sarcoid with a mistletoe extract (Viscum album austriacus). J Vet Intern Med 2010;24(6):1483–1489.
- Ostermann T, Appelbaum S, Poier D, Boehm K, Raak C, Büssing A. A systematic review and meta-analysis on the survival of cancer patients treated with a fermented Viscum album L. extract (Iscador): an update of findings. Complement Med Res 2020;27(4):260–271.
- Harmsma M, Ummelen M, Dignef W, Tusenius KJ, Ramaekers FC. Effects of mistletoe (Viscum album L.) extracts Iscador on cell cycle and survival of tumor cells. Arzneimittelforschung 2006;56(6A):474–482.
- Eggenschwiler J, von Balthazar L, Stritt B. Mistletoe lectin is not the only cytotoxic component in fermented preparations of Viscum album from white fir (Abies pectinata). BMC Complement Altern Med 2007;7:14.
- Steinborn C, Klemd AM, Sanchez-Campillo AS. Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model. PloS One 2017;12(7):e0181553.
- Delebinski CI, Jaeger S, Kemnitz-Hassanin K, Henze G, Lode HN, Seifert GJ. A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Cell Prolif 2012;45(2):176–187.
- Duong Van Huyen JP, Delignat S, Kazatchkine MD, Kaveri SV. Comparative study of the sensitivity of lymphoblastoid and transformed monocytic cell lines to the cytotoxic effects of Viscum album extracts of different origin. Chemotherapy 2003;49(6):298–302.
- Delebinski CI, Twardziok M, Kleinsimon S. A natural combination extract of Viscum album L. containing both triterpene acids and lectins is highly effective against AML in vivo. PLoS One 2015;10(8):e0133892.
- Kleinsimon S, Kauczor G, Jaeger S, Eggert A, Seifert G, Delebinski C. ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs. BMC Complement Altern Med 2017;17(1):26.
- Elluru SR, Duong Van Huyen JP, Delignat S. Antiangiogenic properties of Viscum album extracts are associated with endothelial cytotoxicity. Anticancer Res 2009;29(8):2945–2950.
- Pryme IF, Bardocz S, Pusztai A, Ewen SWB. Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins. Histol Histopathol 2006;21(3):285–299.
- Heinzerling L, von Baehr V, Liebenthal C, von Baehr R, Volk HD. Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo. J Clin Immunol 2006;26(4):347–359.
- Christen-Clottu O, Klocke P, Burger D, Gerber V. Eine randomisierte placebo-kontrollierte Studie zur Behandlung des Equinen Sarkoids bei Pferden mit Viscum album (Iscador® P). In: Scheer R, Alban S, Becker H, et al., eds. Die Mistel in der Tumortherapie 3 KVC Verlag. Essen: Deutschland; 2013:463-473.
- Christen-Clottu U, Reif MOB. Fallserie zur oralen Verwendung eines Mistelextraktes (Viscum album L.) beim equinen Sarkoid. Zeitschrift für Phytotherapie 2022;43(1):P61.
- Biegel U, Ruess-Melzer K, Klocke P. Orally administered Viscum album Quercus dilutions in the therapy of feline fibrosarcoma in cats. Phytomedicine 2011;18:18.
- Haspeslagh M, Gerber V, Knottenbelt DC, Schupbach G, Martens A, Koch C. The clinical diagnosis of equine sarcoids-part 2: assessment of case features typical of equine sarcoids and validation of a diagnostic protocol to guide equine clinicians in the diagnosis of equine sarcoids. Vet J 2018;240:14–18.
- O'Brien RG, Castelloe JM. Exploiting the link between the Wilcoxon-Mann-Whitney test and a simple odds statistic. Stat Data Anal 2006.
- Mählmann K, Hamza E, Marti E. Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease. Vet J 2014;202(3):516–521.
- Thomsen. Total surface calculation. Thomsen 2004.
- Läuter J. Exact t- und F-tests for analysing studies with multiple endpoints. Biometrics 1996;52:964–970.
- Offer KS, Dixon CE, Sutton DGM. Treatment of equine sarcoids: a systematic review. Equine Vet J 2023;56:12–25.
- Berruex F, Gerber V, Wohlfender FD, Burger D, Koch C. Clinical course of sarcoids in 61 Franches-Montagnes horses over a 5-7 year period. Vet Q 2016;36(4):189–196.
- Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2002;41(9):661–680.
- Clark MA, Hirst BH, Jepson MA. Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev 2000;43(2–3):207–223.
- Lyu SY, Park WB. Transport of mistletoe lectin by M cells in human intestinal follicle-associated epithelium (FAE) in vitro. Arch Pharm Res 2008;31(12):1613–1621.
- Lyu SY, Park WB. Mistletoe lectin transport by M-cells in follicle-associated epithelium (FAE) and IL-12 secretion in dendritic cells situated below FAE in vitro. Arch Pharm Res 2010;33(9):1433–1441.
- Yousefi M, Naderi Farsani M, Ghafarifarsani H, Hoseinifar SH, Van Doan H. The effects of dietary supplementation of mistletoe (Viscum album) extract on the growth performance, antioxidant, and innate, immune responses of rainbow trout (Oncorhynchus mykiss). Aquaculture 2021;536:736385.
- Pryme IF, Bardocz S, Pusztai A, Ewen SWB. Dietary mistletoe lectin supplementation and reduced growth of a murine non-Hodgkin lymphoma. Histol Histopathol 2002;17(1):261–271.
- . Equine dermatology-E-book. Elsevier Health Sciences; 2010.
- Knottenbelt DC. Pascoe's principles and practice of equine dermatology E-book: Pascoe's principles and practice of equine dermatology E-book. Elsevier Health Sciences; 2009.
- Nasir L, Campo MS. Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids. Vet Dermatol 2008;19(5):243–254.
- Christen G, Gerber V, Dolf G, Burger D, Koch C. Inheritance of equine sarcoid disease in Franches-Montagnes horses. Vet J 2014;199(1):68–71.
- Staiger EA, Tseng CT, Miller D. Host genetic influence on papillomavirus-induced tumors in the horse. Int J Cancer 2016;139(4):784–792.
- Jandova V, Klukowska-Rötzler J, Dolf G. Whole genome scan identifies several chromosomal regions linked to equine sarcoids. Schweiz Arch Tierheilkd 2012;154(1):19–25.
- Gysens L, Martens A, Haspeslagh M. Cross-sectional comparison of superficial swab and fine-needle aspiration: improving the diagnostic workup of horses with sarcoids. Vet J 2022;289:105916.
- Martens A, De Moor A, Ducatelle R. PCR detection of bovine papilloma virus DNA in superficial swabs and scrapings from equine sarcoids. Vet J 2001;161(3):280–286.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists