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Mistletoe in oncological treatment: a systematic review

Part 2: quality of life and toxicity of cancer treatment
  • M. Freuding
  • C. Keinki
  • S. Kutschan
  • O. Micke
  • J. Buentzel
  • Jutta HuebnerEmail author
Review – Clinical Oncology

Abstract

Purpose

One important goal of any cancer therapy is to improve or maintain quality of life. In this context, mistletoe treatment is discussed to be highly controversial. The aim of this systematic review is to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments.

Methods

In September and October 2017, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and “Science Citation Index Expanded” (Web of Science) were systematically searched.

Results

The search strategy identified 3647 articles and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Regarding quality of life, 17 publications reported results. Studies with better methodological quality show less or no effects on quality of life.

Conclusions

With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Keywords

Mistletoe Cancer Complementary and alternative medicine (CAM) Patient-relevant outcomes 

Notes

Acknowledgements

The authors want to thank Dajana Daum, Catalina Hoppe, Gunnar Voß and Louisa Wortmann for supporting in data extraction/data management and duplicate search.

Funding

The work of MF was funded in parts (search of the literature, title-abstract screening) by the German Guideline “S3 Leitlinie Komplementärmedizin in der Behandlung von onkologischen PatientInnen (Registernummer 032-055OL)” funded by the German Cancer Aid (Fördernummer 11583) within the German Guideline Program in Oncology. Furthermore, the work of MF was funded in parts (evidence table) by the working group Prevention and Integrative Oncology of the German Cancer Society.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

432_2018_2838_MOESM1_ESM.docx (46 kb)
Supplementary material 1 (DOCX 45 KB)

References

  1. Aaronson NK et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376CrossRefGoogle Scholar
  2. Bar-Sela G, Wollner M, Hammer L, Agbarya A, Dudnik E, Haim N (2013) Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: a randomised phase II study European. J Cancer 49:1058–1064Google Scholar
  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424.  https://doi.org/10.3322/caac.21492 CrossRefGoogle Scholar
  4. Bussing A, Raak C, Ostermann T (2012) Quality of life and related dimensions in cancer patients treated with mistletoe extract (iscador): a meta-analysis. Evid Based Complement Altern Med eCAM 2012:219402.  https://doi.org/10.1155/2012/219402 Google Scholar
  5. Cazacu M et al (2003) The influence of isorel on the advanced colorectal cancer. Cancer Biother Radiopharm 18:27–34CrossRefGoogle Scholar
  6. Cella DF et al (1993) The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 11:570–579.  https://doi.org/10.1200/jco.1993.11.3.570 CrossRefGoogle Scholar
  7. Coates A, Glasziou P, McNeil D (1990) On the receiving end—III. Measurement of quality of life during cancer chemotherapy. Ann Oncol 1:213–217CrossRefGoogle Scholar
  8. Deutschinoff G, Friedrich C, Dott U, Voigtmann R, Pientka L (2005) Lebensqualität in der Onkologie—Status Quo und Ausblick [Quality of life in oncology—status quo and outlook]. Der Onkologe 11:164–172.  https://doi.org/10.1007/s00761-004-0825-x CrossRefGoogle Scholar
  9. El-Kolaly RM, Abo-Elnasr M, El-Guindy D (2016) Outcome of pleurodesis using different agents in management of malignant pleural effusion Egyptian. J Chest Dis Tuberc 65:435–440CrossRefGoogle Scholar
  10. Ernst E, Schmidt K, Steuer-Vogt MK (2003) Mistletoe for cancer? A systematic review of randomised clinical trials. Int J Cancer 107(2):262–267CrossRefGoogle Scholar
  11. Gaafar R, Abdel Rahman ARM, Aboulkasem F, El Bastawisy A (2014) Mistletoe preparation (Viscum Fraxini-2) as palliative treatment for malignant pleural effusion: a feasibility study with comparison to bleomycin. Ecancermedicalscience 8:424.  https://doi.org/10.3332/ecancer.2014.424 Google Scholar
  12. Goebell PJ, Otto T, Suhr J, Rubben H (2002) Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168:72–75CrossRefGoogle Scholar
  13. Grossarth-Maticek R, Ziegler R (2006a) Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador). Forschende Komplementarmedizin (2006) 13:285–292Google Scholar
  14. Grossarth-Maticek R, Ziegler R (2006b) Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis. Eur J Med Res 11:485–495Google Scholar
  15. Grossarth-Maticek R, Ziegler R (2007a) Efficacy and safety of the long-term treatment of melanoma with a mistletoe preparation (Iscador). Schweizerische Zeitschrift fur GanzheitsMedizin 19:325–332CrossRefGoogle Scholar
  16. Grossarth-Maticek R, Ziegler R (2007b) Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Forschende Komplementarmedizin (2006) 14:140–147Google Scholar
  17. Grossarth-Maticek R, Ziegler R (2007c) Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador. Arzneimittelforschung 57:665–678Google Scholar
  18. Grossarth-Maticek R, Ziegler R (2008) Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res 13:107–120Google Scholar
  19. Grossarth-Maticek R, Eysenck HJ, Boyle GJ (1995) Method of test administration as a factor in test validity: the use of a personality questionnaire in the prediction of cancer and coronary heart disease. Behav Res Ther 33:705–710CrossRefGoogle Scholar
  20. Heiny BM, Albrecht V (1997) Complementary modes of therapy with mistletoe lectin-1. Medizinische Welt 48:419–423Google Scholar
  21. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M (2008) Mistletoe therapy in oncology. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD003297 Google Scholar
  22. Horneber M, Bueschel G, Dennert G, Less D, Ritter E, Zwahlen M (2012) How many cancer patients use complementary and alternative medicine: a systematic review and metaanalysis. Integr Cancer Ther 11:187–203.  https://doi.org/10.1177/1534735411423920 CrossRefGoogle Scholar
  23. Hübner J (2015) Comment on ‘Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial: several flaws. Deutsches Arzteblatt International 112:9–9Google Scholar
  24. Huebner J et al (2014) User rate of complementary and alternative medicine (CAM) of patients visiting a counseling facility for CAM of a German comprehensive cancer center. Anticancer Res 34:943–948Google Scholar
  25. Karnofsky DA, Burchenal JH (1949) The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM (ed) Evaluation of chemotherapeutic agents. Columbia Univ Press, New York, pp 191–205Google Scholar
  26. Khan FA, Akhtar SS, Sheikh MK (2005) Cancer treatment—objectives and quality of life issues Malays. J Med Sci 12:3–5Google Scholar
  27. Kienle GS, Kiene H (2007) Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res 12:103–119Google Scholar
  28. Kienle GS, Kiene H (2010) Review article: influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther 9:142–157CrossRefGoogle Scholar
  29. Kienle GS, Glockmann A, Schink M, Kiene H (2009) Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res 28:79CrossRefGoogle Scholar
  30. Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R (2012) Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma—a randomized, controlled pilot study. BMC Complement Altern Med 12:172CrossRefGoogle Scholar
  31. Kleeberg UR et al (2004) Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness> 3 mm) or regional lymph node metastasis. Eur J Cancer 40:390–402CrossRefGoogle Scholar
  32. Lange-Lindberg A-M, Velasco Garrido M, Busse R (2006) Mistletoe treatments for minimising side effects of anticancer chemotherapy. GMS Health Technol Assess 2:1–8Google Scholar
  33. Lenartz D, Stoffel B, Menzel J, Beuth J (1996) Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 16:3799–3802Google Scholar
  34. Lenartz D, Dott U, Menzel J, Schierholz JM, Beuth J (2000) Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 20:2073–2076Google Scholar
  35. Longhi A, Mariani E, Kuehn J (2009) A randomized study with adjuvant mistletoe versus oral Etoposide on post relapse disease-free survival in osteosarcoma patients. Eur J Integr Med 1:31–39CrossRefGoogle Scholar
  36. Longhi A, Reif M, Mariani E, Ferrari S (2014) A randomized study on postrelapse disease-free survival with adjuvant mistletoe versus oral etoposide in osteosarcoma patients. Evid Based Complement Altern Med eCAM 2014:210198.  https://doi.org/10.1155/2014/210198 CrossRefGoogle Scholar
  37. Melzer J, Iten F, Hostanska K, Saller R (2009) Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forschende Komplementarmedizin (2006) 16:217–226Google Scholar
  38. Piao BK, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS (2004) Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Res 24:303–309Google Scholar
  39. Schipper H, Clinch J, McMurray A, Levitt M (1984) Measuring the quality of life of cancer patients: the Functional Living Index-Cancer: development and validation. J Clin Oncol 2:472–483.  https://doi.org/10.1200/jco.1984.2.5.472 CrossRefGoogle Scholar
  40. Semiglasov VF, Stepula VV, Dudov A, Lehmacher W, Mengs U (2004) The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 24:1293–1302Google Scholar
  41. Semiglazov VF, Stepula VV, Dudov A, Schnitker J, Mengs U (2006) Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 26:1519–1529Google Scholar
  42. Spitzer WO et al (1981) Measuring the quality of life of cancer patients: a concise QL-index for use by physicians. J Chronic Dis 34:585–597CrossRefGoogle Scholar
  43. Steuer-Vogt MK et al (2001) The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial European. J Cancer 37:23–31Google Scholar
  44. Steuer-Vogt MK, Bonkowsky V, Scholz M, Fauser C, Licht K, Ambrosch P (2006) Influence of ML-1 standardized mistletoe extract on the quality of life in head and neck cancer patients. Hno 54:277–286CrossRefGoogle Scholar
  45. Stub T, Quandt SA, Arcury TA, Sandberg JC, Kristoffersen AE, Musial F, Salamonsen A (2016) Perception of risk and communication among conventional and complementary health care providers involving cancer patients’ use of complementary therapies: a literature review. BMC Complement Altern Med 16:353.  https://doi.org/10.1186/s12906-016-1326-3 CrossRefGoogle Scholar
  46. Troger W, Jezdic S, Zdrale Z, Tisma N, Hamre HJ, Matijasevic M (2009) Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone Breast cancer. Basic Clin Res 3:35–45Google Scholar
  47. Troger W, Zdrale Z, Stankovic N, Matijasevic M (2012) Five-year follow-up of patients with early stage breast cancer after a randomized study comparing additional treatment with Viscum album (L.) extract to chemotherapy alone. Breast Cancer Basic Clin Res 6:173–180.  https://doi.org/10.4137/BCBCR.S10558 CrossRefGoogle Scholar
  48. Troger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M (2013) Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer 49:3788–3797CrossRefGoogle Scholar
  49. Troger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M (2014a) Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsches Arzteblatt international 111:493–502 (433 p following 502) Google Scholar
  50. Troger W, Zdrale Z, Tisma N, Matijasevic M (2014b) Additional therapy with a mistletoe product during adjuvant chemotherapy of breast cancer patients improves quality of life: an open randomized clinical pilot trial. Evid Based Complement Altern Med eCAM 2014:430518.  https://doi.org/10.1155/2014/430518 CrossRefGoogle Scholar
  51. Troger W, Zdrale Z, Stankovic N (2016) Five-Year follow-up of patients with early stage breast cancer after a randomized study with Viscum album (L.) extract. Deutsche Zeitschrift fur Onkologie 48:105–110CrossRefGoogle Scholar
  52. WHO (1996) What quality of life? The WHOQOL Group. World Health Organization Quality of Life. Assessment World Health Forum 17:354–356Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Klinik für Innere Medizin II, Hämatologie und Internistische OnkologieUniversitätsklinikum JenaJenaGermany
  2. 2.Klinik für Strahlentherapie und RadioonkologieFranziskus HospitalBielefeldGermany
  3. 3.Klinik für Hals-Nasen-Ohren-HeilkundeSüdharzklinikum NordhausenNordhausenGermany

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