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

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.

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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.

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Corresponding author

Correspondence to Dr. med. Nadja Ebert.

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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).

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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 (2020). https://doi.org/10.1007/s00066-020-01684-y

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Keywords

  • HNSCC
  • Oral mucositis
  • Radiation side effect
  • Supportive treatment
  • Herbal tea