Skip to main content

Advertisement

SpringerLink
Log in

Results of a randomized controlled phase III trial: efficacy of polyphenol-containing cystus® tea mouthwash solution for the reduction of mucositis in head and neck cancer patients undergoing external beam radiotherapy

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

To determine the effect of Cystus® tea (Naturprodukte Dr. Pandalis GmbH & Co. KG) as mouthwash compared to sage tea on oral mucositis in patients undergoing radio(chemo)therapy for head and neck cancer.

Methods

In this randomized, prospective phase III study, 60 head and neck cancer patients with primary or postoperative radio(chemo)therapy were included between 04/2012 and 06/2014. They received either sage or Cystus® tea for daily mouthwash under therapy. Mucositis was scored twice a week following the Radiation Therapy Oncology Group and the European Organization for Research and Treatment Cancer (RTOG/EORTC) scoring system. Dental parameters were also recorded. Statistical evaluation of the primary endpoint was performed using t‑test and log rank test.

Results

Data from 57 patients could be evaluated. Patient characteristics showed no significant difference between the two groups (n = 27 sage; n = 30 Cystus®). A total of 55 patients received the prescribed dose (60–66 Gy postoperative; 70–76.8 Gy primary). Mucositis grade 3 was observed in 23 patients (n = 11 sage; n = 12 Cystus®) and occurred between day 16 and 50 after start of therapy. There was no significant difference between the two groups in latency (p = 0.75) and frequency (p = 0.85) of the occurrence of mucositis grade 3. The self-assessment of the oral mucosa and the tolerability of the tea also showed no significant differences. Occurrence of dental pathologies appeared to increase over time after radiotherapy.

Conclusion

Cystus® and sage tea have a similar effect on the occurrence of radiation-induced mucositis regarding latency and incidence. Cystus® tea mouthwash solution is tolerated well and can be applied in addition to intensive oral care and hygiene along with the application of fluorides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S, Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer, International Society of Oral Oncology (MASCC/ISOO) (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120(10):1453–1461. https://doi.org/10.1002/cncr.28592

    Article  PubMed  PubMed Central  Google Scholar 

  2. Epstein JB, Beaumont JL, Gwede CK, Murphy B, Garden AS, Meredith R, Le QT, Brizel D, Isitt J, Cella D (2007) Longitudinal evaluation of the oral mucositis weekly questionnaire-head and neck cancer, a patient-reported outcomes questionnaire. Cancer 109(9):1914–1922. https://doi.org/10.1002/cncr.22620

    Article  PubMed  Google Scholar 

  3. Withers HR, Maciejewski B, Taylor JM, Hliniak A (1988) Accelerated repopulation in head and neck cancer. Front Radiat Ther Oncol 22:105–110

    Article  CAS  PubMed  Google Scholar 

  4. Bentzen SM, Thames HD (1991) Clinical evidence for tumor clonogen regeneration: interpretations of the data. Radiother Oncol 22(3):161–166

    Article  CAS  PubMed  Google Scholar 

  5. Hong CH, Napenas JJ, Hodgson BD, Stokman MA, Mathers-Stauffer V, Elting LS, Spijkervet FK, Brennan MT, Multi-national Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) (2010) A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer 18(8):1007–1021. https://doi.org/10.1007/s00520-010-0873-2

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gupta N, Pal M, Rawat S, Grewal MS, Garg H, Chauhan D, Ahlawat P, Tandon S, Khurana R, Pahuja AK, Mayank M, Devnani B (2015) Radiation-induced dental caries, prevention and treatment—a systematic review. Natl J Maxillofac Surg 6(2):160–166. https://doi.org/10.4103/0975-5950.183870

    Article  PubMed  PubMed Central  Google Scholar 

  7. Aguiar GP, Jham BC, Magalhaes CS, Sensi LG, Freire AR (2009) A review of the biological and clinical aspects of radiation caries. J Contemp Dent Pract 10(4):83–89

    Article  PubMed  Google Scholar 

  8. Kufta K, Forman M, Swisher-McClure S, Sollecito TP, Panchal N (2018) Pre-Radiation dental considerations and management for head and neck cancer patients. Oral Oncol 76:42–51. https://doi.org/10.1016/j.oraloncology.2017.11.023

    Article  PubMed  Google Scholar 

  9. Nagi R, Patil DJ, Rakesh N, Jain S, Sahu S (2018) Natural agents in the management of oral mucositis in cancer patients-systematic review. J Oral Biol Craniofac Res 8(3):245–254. https://doi.org/10.1016/j.jobcr.2017.12.003

    Article  PubMed  Google Scholar 

  10. Hannig C, Spitzmuller B, Al-Ahmad A, Hannig M (2008) Effects of cistus-tea on bacterial colonization and enzyme activities of the in situ pellicle. J Dent 36(7):540–545. https://doi.org/10.1016/j.jdent.2008.04.002

    Article  CAS  PubMed  Google Scholar 

  11. Kalus U, Grigorov A, Kadecki O, Jansen JP, Kiesewetter H, Radtke H (2009) Cistus incanus (CYSTUS052) for treating patients with infection of the upper respiratory tract. A prospective, randomised, placebo-controlled clinical study. Antiviral Res 84(3):267–271. https://doi.org/10.1016/j.antiviral.2009.10.001

    Article  CAS  PubMed  Google Scholar 

  12. Attaguile G, Russo A, Campisi A, Savoca F, Acquaviva R, Ragusa N, Vanella A (2000) Antioxidant activity and protective effect on DNA cleavage of extracts from cistus incanus L. and cistus monspeliensis L. Cell Biol Toxicol 16(2):83–90

    Article  CAS  PubMed  Google Scholar 

  13. Hannig C, Sorg J, Spitzmuller B, Hannig M, Al-Ahmad A (2009) Polyphenolic beverages reduce initial bacterial adherence to enamel in situ. J Dent 37(7):560–566. https://doi.org/10.1016/j.jdent.2009.03.017

    Article  CAS  PubMed  Google Scholar 

  14. Wittpahl G, Kolling-Speer I, Basche S, Herrmann E, Hannig M, Speer K, Hannig C (2015) The polyphenolic composition of cistus incanus herbal tea and its antibacterial and anti-adherent activity against streptococcus mutans. Planta Med 81(18):1727–1735. https://doi.org/10.1055/s-0035-1557822

    Article  CAS  PubMed  Google Scholar 

  15. Kalus U, Kiesewetter H, Radtke H (2010) Effect of CYSTUS052 and green tea on subjective symptoms in patients with infection of the upper respiratory tract. Phytother Res 24(1):96–100. https://doi.org/10.1002/ptr.2876

    Article  PubMed  Google Scholar 

  16. Ehrhardt C, Hrincius ER, Korte V, Mazur I, Droebner K, Poetter A, Dreschers S, Schmolke M, Planz O, Ludwig S (2007) A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antiviral Res 76(1):38–47. https://doi.org/10.1016/j.antiviral.2007.05.002

    Article  CAS  PubMed  Google Scholar 

  17. Steinmann D, Eilers V, Beynenson D, Buhck H, Fink M (2012) Effect of Traumeel S on pain and discomfort in radiation-induced oral mucositis: a preliminary observational study. Altern Ther Health Med 18(4):12–18

    PubMed  Google Scholar 

  18. Budach V, Stuschke M, Budach W, Baumann M, Geismar D, Grabenbauer G, Lammert I, Jahnke K, Stueben G, Herrmann T, Bamberg M, Wust P, Hinkelbein W, Wernecke KD (2005) Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German cancer society 95-06 prospective randomized trial. J Clin Oncol 23(6):1125–1135. https://doi.org/10.1200/JCO.2005.07.010

    Article  CAS  PubMed  Google Scholar 

  19. Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5):1341–1346. https://doi.org/10.1016/0360-3016(95)00060-C

    Article  CAS  PubMed  Google Scholar 

  20. Pitts NB, Ekstrand KR, Foundation I (2013) International caries detection and assessment system (ICDAS) and its international caries classification and management system (ICCMS)—methods for staging of the caries process and enabling dentists to manage caries. Community Dent Oral Epidemiol 41(1):e41–52. https://doi.org/10.1111/cdoe.12025

    Article  CAS  PubMed  Google Scholar 

  21. Lieshout HF, Bots CP (2014) The effect of radiotherapy on dental hard tissue—a systematic review. Clin Oral Investig 18(1):17–24. https://doi.org/10.1007/s00784-013-1034-z

    Article  CAS  PubMed  Google Scholar 

  22. Lange DE, Plagmann HE, Eenboom A, Promesberger A (1977) Clinical methods for the objective evaluation of oral hygiene. Dtsch Zahnärztl Z 32(1):44–47

    CAS  PubMed  Google Scholar 

  23. Doerr W, Groetz KA, Hartmann JT, Riesenbeck D (2007) Orale Mukositis. Onkologe 13(2):150–157

    Article  Google Scholar 

  24. Beheshti-Rouy M, Azarsina M, Rezaie-Soufi L, Alikhani MY, Roshanaie G, Komaki S (2015) The antibacterial effect of sage extract (salvia officinalis) mouthwash against streptococcus mutans in dental plaque: a randomized clinical trial. Iran J Microbiol 7(3):173–177

    PubMed  PubMed Central  Google Scholar 

  25. Moricz AM, Szeremeta D, Knas M, Dlugosz E, Ott PG, Kowalska T, Sajewicz M (2018) Antibacterial potential of the cistus incanus L. phenolics as studied with use of thin-layer chromatography combined with direct bioautography and in situ hydrolysis. J Chromatogr A 1534:170–178. https://doi.org/10.1016/j.chroma.2017.12.056

    Article  CAS  PubMed  Google Scholar 

  26. Qnais EY, Abu-Dieyeh M, Abdulla FA, Abdalla SS (2010) The antinociceptive and anti-inflammatory effects of salvia officinalis leaf aqueous and butanol extracts. Pharm Biol 48(10):1149–1156. https://doi.org/10.3109/13880200903530763

    Article  PubMed  Google Scholar 

  27. Gericke S, Lubken T, Wolf D, Kaiser M, Hannig C, Speer K (2018) Identification of new compounds from sage flowers (salvia officinalis L.) as markers for quality control and the influence of the manufacturing technology on the chemical composition and antibacterial activity of sage flower extracts. J Agric Food Chem 66(8):1843–1853. https://doi.org/10.1021/acs.jafc.8b00581

    Article  CAS  PubMed  Google Scholar 

  28. Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, Komaroff E, Nalysnyk L, Zilberberg MD (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol 66(3):253–262

    Article  PubMed  Google Scholar 

  29. Mallick S, Benson R, Rath GK (2016) Radiation induced oral mucositis: a review of current literature on prevention and management. Eur Arch Otorhinolaryngol 273(9):2285–2293. https://doi.org/10.1007/s00405-015-3694-6

    Article  PubMed  Google Scholar 

  30. Frydrych AM, Slack-Smith LM, Parsons R (2017) Compliance of post-radiation therapy head and neck cancer patients with caries preventive protocols. Aust Dent J 62(2):192–199. https://doi.org/10.1111/adj.12491

    Article  CAS  PubMed  Google Scholar 

  31. Smullen J, Koutsou GA, Foster HA, Zumbe A, Storey DM (2007) The antibacterial activity of plant extracts containing polyphenols against streptococcus mutans. Caries Res 41(5):342–349. https://doi.org/10.1159/000104791

    Article  CAS  PubMed  Google Scholar 

  32. Carvalho JC, Schiffner U (2018) Dental caries in European adults and senior citizens 1996–2016: ORCA saturday afternoon symposium in Greifswald, Germany—part II. Caries Res 53(3):242–252. https://doi.org/10.1159/000492676

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to gratefully acknowledge financial support from Naturprodukte Dr. Pandalis GmbH & Co. KG. We thank our participating patients for their willingness to support this study. The personnel of the clinical trials office at OncoRay Dresden, nurses and study nurses in the patient care of the Department of Radiotherapy are gratefully acknowledged. We would like to dedicate this paper to our colleague Prof. Wolfgang Dörr who passed away in October 2019.

Funding

The funders Naturprodukte Dr. Pandalis GmbH & Co. KG of this study had no role in the design, data collection, data analyses, data evaluation, and preparation of the manuscript or decision to submit for publication.

Author information

Authors and Affiliations

  1. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Nadja Ebert, Wahyu Wijaya Hadiwikarta PhD,  Mechthild Krause Prof. Dr. med. &  Michael Baumann Prof. Dr. med.

  2. Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany

    Nadja Ebert,  Steffen Löck,  Mechthild Krause Prof. Dr. med. &  Michael Baumann Prof. Dr. med.

  3. OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany

    Nadja Ebert,  Steffen Löck,  Mechthild Krause Prof. Dr. med. &  Michael Baumann Prof. Dr. med.

  4. German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Nadja Ebert,  Steffen Löck &  Mechthild Krause Prof. Dr. med.

  5. Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Nadja Ebert,  Steffen Löck,  Mechthild Krause Prof. Dr. med. &  Michael Baumann Prof. Dr. med.

  6. Clinic of Operative and Pediatric Dentistry, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany

    Anna Kensche,  Anna Hänsch &  Christian Hannig

  7. Helmholtz-Zentrum Dresden — Rossendorf, Institute of Radiooncology — OncoRay, Dresden, Germany

    Mechthild Krause Prof. Dr. med.

  8. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany

    Mechthild Krause Prof. Dr. med.

  9. Helmholtz Association/Helmholtz-Zentrum Dresden—Rossendorf (HZDR), Dresden—Rossendorf, Germany

    Mechthild Krause Prof. Dr. med.

  10. Ruprecht-Karls-University, Heidelberg, Germany

    Michael Baumann Prof. Dr. med.

Authors
  1. Nadja Ebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Kensche
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steffen Löck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wahyu Wijaya Hadiwikarta PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna Hänsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wolfgang Dörr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mechthild Krause Prof. Dr. med.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Hannig
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Baumann Prof. Dr. med.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadja Ebert.

Ethics declarations

Conflict of interest

N. Ebert, A. Kensche, S. Löck, W.W. Hadiwikarta, A. Hänsch, W. Dörr, M. Krause, C. Hannig and M. Baumann received financial support from Naturprodukte Dr. Pandalis GmbH & Co. KG for this study. The funding had no influence on collection, analyses, and data evaluation. N. Ebert was co-principal investigator for funded research projects to the University of Dresden by Merck KGaA (2014–open). N. Ebert confirms that the above funding source was not involved in the design of this study, the preparation of this paper, the materials used, or the collection, analysis, and interpretation of data. M. Krause declares that within the past 5 years she received funding for her research projects and for educational grants to the University of Dresden IBA (2016), Merck KGaA (2016–2030), Medipan GmbH (2014–2018). As chair of OncoRay (Dresden) she signed/s contracts for her institute(s) and for the staff for research funding and collaborations with different companies. In the past 5 years, M. Baumann attended an advisory board meeting of MERCK KGaA (Darmstadt), for which the University of Dresden received a travel grant. He further received funding for his research projects and for educational grants to the University of Dresden by Teutopharma GmbH (2011–2015), IBA (2016), Bayer AG (2016–2018), Merck KGaA (2014–open), Medipan GmbH (2014–2018). He is on the supervisory board of HI-STEM gGmbH (Heidelberg) for the German Cancer Research Center (DKFZ, Heidelberg) and also member of the supervisory body of the Charité University Hospital, Berlin. As former chair of OncoRay (Dresden) and present CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg), he has been or is still responsible for collaborations with a multitude of companies and institutions, worldwide. In this capacity, he discussed potential projects with and has signed/signs contracts for his institute(s) and for the staff for research funding and/or collaborations with industry and academia, worldwide, including but not limited to pharmaceutical corporations like Bayer, Boehringer Ingelheim, Bosch, Roche and other corporations like Siemens, IBA, Varian, Elekta, Bruker and others. In this role, he was/is further responsible for commercial technology transfer activities of his institute(s), including the DKFZ-PSMA617 related patent portfolio (WO2015055318 (A1), ANTIGEN (PSMA)) and similar intellectual propterty portfolios. Dr. Baumann confirms that to the best of his knowledge none of the above funding sources was involved in the preparation of this paper.

Ethical standards

The study was approved by the institutional ethics committee of the Technische Universität Dresden (EK 281082011). Only patients who met the inclusion criteria and signed a consent form were enrolled in the study and randomized to receive either Cystus® or sage tea.

Additional information

C. Hannig und M. Baumann share last co-authorship.

Availability of data and material

Data were stored at the Department of Radiation Oncology, except for the dental parameters that were stored at the Clinic of Operative Dentistry at the University Medical Center Carl Gustav Carus in Dresden. The data are not deposited in a repository.

Code availability

Statistical analysis and graph creations were performed using R version 3.5.0 (2018-04-23).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ebert, N., Kensche, A., Löck, S. et al. Results of a randomized controlled phase III trial: efficacy of polyphenol-containing cystus® tea mouthwash solution for the reduction of mucositis in head and neck cancer patients undergoing external beam radiotherapy. Strahlenther Onkol 197, 63–73 (2021). https://doi.org/10.1007/s00066-020-01684-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-020-01684-y

Keywords

Search

Navigation