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Mistletoe in oncological treatment: a systematic review

Part 1: survival and safety

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Mistletoe treatment of cancer patients is discussed highly controversial in the scientific literature. Aim of this systematic review is to give an extensive overview about current state of research concerning mistletoe therapy of oncologic patients regarding survival, quality of life and safety.

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 hits 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. Patient relevant endpoints were overall survival (14 studies, n = 1054), progression- or disease-free survival or tumor response (10 studies, n = 1091). Most studies did not show any effect of mistletoe on survival. Especially high quality studies do not show any benefit.

Conclusions

With respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

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References

  • Abreu P, Sanchez R, Mut T, Balaguer D, Latorre I, Rodriguez H (2017) Homeopathic mistletoe adverse reaction mimics nodal involvement in 18F-FDG PET/CT performed for evaluation of response to chemotherapy in lymphoma. Revista Espanola de Medicina Nuclear e Imagen Molecular 36:110–112. https://doi.org/10.1016/j.remn.2016.07.005

    Article  CAS  PubMed  Google Scholar 

  • 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. Eur J Cancer 49:1058–1064

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1155/2012/219402

    Article  Google Scholar 

  • Cazacu M et al (2003) The influence of isorel on the advanced colorectal cancer. Cancer Biother Radiopharm 18:27–34

    Article  CAS  PubMed  Google Scholar 

  • Conrad AC, Muenstedt K, Micke O, Prott FJ, Muecke R, Huebner J (2014) Attitudes of members of the German Society for Palliative Medicine toward complementary and alternative medicine for cancer patients. J Cancer Res Clin Oncol 140:1229–1237. https://doi.org/10.1007/s00432-014-1656-9

    Article  CAS  PubMed  Google Scholar 

  • 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 65:435–440

    Article  Google Scholar 

  • Ernst E, Schmidt K, Steuer-Vogt MK (2003) Mistletoe for cancer? A systematic review of randomised clinical trials. Int J Cancer 107:262–267

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 168:72–75

    Article  PubMed  Google Scholar 

  • 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) 13:285–292

    Google Scholar 

  • 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 11:485–495

    CAS  PubMed  Google Scholar 

  • 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 [German] 19:325–332

    Article  Google Scholar 

  • 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) 14:140–147

    Google Scholar 

  • 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 57:665–678

    CAS  PubMed  Google Scholar 

  • 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 13:107–120

    CAS  PubMed  Google Scholar 

  • Grossarth-Maticek R, Kiene H, Baumgartner SM, Ziegler R (2001) Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 7:57–66 (68–72, 74–56 passim)

    CAS  PubMed  Google Scholar 

  • Hagenah W, Dorges I, Gafumbegete E, Wagner T (1998) Subcutaneous manifestations of a centrocytic non-Hodgkin lymphoma at the injection site of a mistletoe preparation. Deutsche medizinische Wochenschrift (1946) 123:1001–1004 https://doi.org/10.1055/s-2007-1024111

    Article  CAS  Google Scholar 

  • Heiny BM, Albrecht V (1997) Complementary modes of therapy with mistletoe lectin-1. Medizinische Welt [German] 48:419–423

    Google Scholar 

  • Heiny BM, Albrecht V, Beuth J (1998) Correlation of immune cell activities and beta-endorphin release in breast carcinoma patients treated with galactose-specific lectin standardized mistletoe extract. Anticancer Res 18:583–586

    CAS  PubMed  Google Scholar 

  • Henf A, Wesselmann S, Huthmann D, Muenstedt K, Huebner J, On behalf of the Working Group P, Intergrative Oncology of the German Cancer Society J (2014) Complementary and alternative medicine in German Cancer Centers. Oncol Res Treat 37:390–394. https://doi.org/10.1159/000364897

    Article  Google Scholar 

  • Higgins JPT, Altman DG, Sterne JAC (2017) Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (eds) Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). Cochrane

  • Horneber MA, Bueschel G, Huber R, Linde K, Rostock M (2008) Mistletoe therapy in oncology Cochrane Database of Syst Revi 107:CD003297

    Google Scholar 

  • Hubner J, Phieler F (2009) Hypersensitivity reaction to oxaliplatinum recurrence during mistletoe therapy? Tumor Diagnostik Therapie [German] 30:36–39

    Google Scholar 

  • Huebner J (2008) Komplementäre Onkologie - Supportive Maßnahmen und evidenzbasierte Empfehlungen. Schattauer, Stuttgart

    Google Scholar 

  • Hutt N, Kopferschmitt-Kubler M, Cabalion J, Purohit A, Alt M, Pauli G (2001) Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.). Allergologia et immunopathologia 29:201–203

    Article  CAS  PubMed  Google Scholar 

  • Kienle GS, Kiene H (2007) Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res 12:103–119

    CAS  PubMed  Google Scholar 

  • 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 9:142–157

    Article  PubMed  Google Scholar 

  • 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 28:79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 12:172

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 40:390–402

    Article  CAS  Google Scholar 

  • Lange-Lindberg A-M, Velasco Garrido M, Busse R (2006) Mistletoe treatments for minimising side effects of anticancer chemotherapy. GMS Health Technol Assess 2:Doc18

    PubMed  PubMed Central  Google Scholar 

  • 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 16:3799–3802

    CAS  PubMed  Google Scholar 

  • 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 20:2073–2076

    CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1155/2014/210198

    Article  Google Scholar 

  • 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) 16:217–226

    Google Scholar 

  • Ostermann T, Bussing A (2012) Retrolective studies on the survival of cancer patients treated with mistletoe extracts: a meta-analysis. Explore J Sci Heal 8:277–281

    Google Scholar 

  • Ostermann T, Raak C, Bussing A (2009) Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review. BMC Cancer 9:451

    Article  PubMed  PubMed Central  Google Scholar 

  • Ott IM et al (2015) Attitude of oncology/hematology nurses from German speaking countries towards complementary and alternative medicine. Trace Elem Electrolytes 32:74–80

    Article  Google Scholar 

  • 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 24:303–309

    CAS  PubMed  Google Scholar 

  • Robinson A, McGrail MR (2004) Disclosure of CAM use to medical practitioners: a review of qualitative and quantitative studies. Complement Ther Med 12:90–98. https://doi.org/10.1016/j.ctim.2004.09.006

    Article  CAS  PubMed  Google Scholar 

  • Saxe GA, Madlensky L, Kealey S, Wu DP, Freeman KL, Pierce JP (2008) Disclosure to physicians of CAM use by breast cancer patients: findings from the Women’s Healthy Eating and Living Study. Integr Cancer Ther 7:122–129. https://doi.org/10.1177/1534735408323081

    Article  PubMed  PubMed Central  Google Scholar 

  • Schierholz JM et al (2003) Complementary cancer therapy with standardized mistletoe extracts. Results of a controlled prospective multicentric randomized clinical trial. [German] Deutsche Zeitschrift fur Onkologie 35:186–194

    Article  Google Scholar 

  • Schink M et al (2007) Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. a randomized phase III trial. Forschende Komplementarmedizin (2006) 14:9–17

    Google Scholar 

  • 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 24:1293–1302

    CAS  PubMed  Google Scholar 

  • Semiglasov 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 26:1519–1529

    Google Scholar 

  • Shaw HS, Hobbs KB, Kroll DJ, Seewaldt VL (2004) Delayed-type hypersensitivity reaction with iscador M given in combination with cytotoxic chemotherapy. J Clin Oncol 22:4432–4434. https://doi.org/10.1200/jco.2004.04.140

    Article  PubMed  Google Scholar 

  • Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F (2014) Adverse drug reactions and expected effects to therapy with subcutaneous mistletoe extracts (Viscum album L.) in cancer patients. Evid Based Complement Altern Med eCAM 2014. https://doi.org/10.1155/2014/724258

    Article  Google Scholar 

  • 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 37:23–31

    CAS  Google Scholar 

  • 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 54:277–286

    Article  CAS  PubMed  Google Scholar 

  • Styczynski J, Wysocki M (2006) Alternative medicine remedies might stimulate viability of leukemic cells. Pediatr Blood Cancer 46:94–98. https://doi.org/10.1002/pbc.20513

    Article  PubMed  Google Scholar 

  • Thies A, Nugel D, Pfuller U, Moll I, Schumacher U (2005) Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro. Toxicology 207:105–116. https://doi.org/10.1016/j.tox.2004.09.009

    Article  CAS  PubMed  Google Scholar 

  • Thronicke A, Steele M, Grah C, Matthes B, Schad F (2017) Clinical safety of combinational therapy of immune checkpoint inhibitors and Viscum album L. in patients with advanced or metastasized cancer. Journal of Thorac Oncol 12(1 Supplement 1):S1295–S1296

    Article  Google Scholar 

  • Trimborn A et al (2013) Attitude of employees of a university clinic to complementary and alternative medicine in oncology. Ann Oncology 24:2641–2645. https://doi.org/10.1093/annonc/mdt299

    Article  CAS  Google Scholar 

  • Troger W (2011) Connection between quality of life and neutropenia in breast cancer patients who were solely treated with chemotherapy or additionally with mistletoe therapy: results of a randomized study. Deutsche Zeitschrift fur Onkologie [German] 43:58–67

    Article  Google Scholar 

  • 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 3:35–45

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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 European. J Cancer 49:3788–3797

    CAS  Google Scholar 

  • 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. Deutsch Arzteblatt Int 111:493–502

    Google Scholar 

  • 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. https://doi.org/10.1155/2014/430518

    Article  Google Scholar 

  • 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. [German]. Deutsche Zeitschrift fur Onkologie 48:105–110

    Article  Google Scholar 

  • Tröger W, Galun D, Reif M, Schumann A, Stankovi N, Milićevi 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 (Oxford Engl 1990) 49:3788–3797. https://doi.org/10.1016/j.ejca.2013.06.043

    Article  Google Scholar 

  • Tröger W, Galun D, Reif M, Schumann A, Stankovi N, Milićevi M (2014) Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Deutsch Arzteblatt Int 111:493–502. https://doi.org/10.3238/arztebl.2014.0493

    Article  Google Scholar 

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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.

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Correspondence to Jutta Huebner.

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Freuding, M., Keinki, C., Micke, O. et al. Mistletoe in oncological treatment: a systematic review. J Cancer Res Clin Oncol 145, 695–707 (2019). https://doi.org/10.1007/s00432-018-02837-4

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