International Coordination
Anthroposophic Medicine
School of Spiritual Science
Medical Section at the Goetheanum

Cancer disease, mistletoe treatment

read more

Mistletoe extracts (Viscum album L., VAE) are widely used integrative cancer care treatments, particularly in Europe (1-5). They are an old herbal remedy (6, 7) and were introduced as cancer treatment in 1920 by Rudolf Steiner and Ita Wegman, founders of Anthroposophic Medicine (8). Viscum album is a hemiparasitic shrub, growing on different host trees. Different preparations are available for the treatment of cancer (currently Abnobaviscum®, Helixor®, Iscador®, Iscucin® and Lektinol®). They are available from different host trees such as oak, apple, pine and many others. They are applied parenteral, particularly subcutaneous, but also intravenous, intratumoural, intrapleural, intraperitoneal and other sites.

Several pharmacologically active compounds have been isolated from VAE, such as mistletoe lectins (ML I, II and III) (9), viscotoxins (10, 11), oligo- and polysaccharides (12, 13), lipophilic extracts (14) and various others (6, 7). Currently VAE triterpenes are gaining great interest. (15-19) The most prominent properties of VAE are their cytotoxic and growth-inhibiting effects, in vitro, on a variety of human tumour cell lines, lymphocytes and fibroblasts (6, 7). The cytotoxic effects of VAE are mainly due to the apoptosis-inducing mistletoe lectins (20-22), while the viscotoxins induce necrotic cell death (21, 23). VAE are also recognized for their immune-modulating activity: In vitro and in vivo studies have demonstrated activation of monocytes/macrophages, granulocytes, natural killer (NK) cells, NK-cell mediated tumor cell lysis, T-cells (especially T-helper-cells) and the induction of various cytokines (6, 7, 24). VAE also downregulate tumor genes, reduce motility and invasiveness of tumor cells [24), and show antiangiogenetic effects [25). They also possess DNA stabilizing properties, they reduce chromosome damage and improve DNA repair (26-29]. In animals, VAE displays potent antitumour effects when administered either directly into the tumour or systemically (6, 7, 30).

Clinical effectiveness of mistletoe extracts in cancer has been investigated in a great number of studies, among these 43 prospective randomized controlled trials (31-80): They predominantly report significant clinical benefits. With regard to quality of studies and consistency of results, the best evidence concerning efficacy of mistletoe therapy exists for the improvement of quality of life, increase of weight, and improved tolerability of cytoreductive therapies (chemotherapy, radiotherapy, surgery) (33, 81, 82). Regarding survival, a well-designed randomized controlled trial has recently shown a highly significant benefit in advanced pancreatic cancer (32). Other studies showed similar results (30, 83-85). Effectiveness seems to depend on the duration of the mistletoe therapy, in addition to factors relating to dosage, host tree and choice of preparation. Tumour remissions have been repeatedly observed after local application of high dose mistletoe extracts. This finding is consistent with the preclinical research on cytotoxicity and treatment of tumors in animals. During customary low-dose mistletoe therapy, tumour remissions are rare exceptions. Tumor remissions have therefore been reported primarily in small studies, case series and single cases. (e.g. (30, 84, 86-96))

According to highly experienced practitioners much improved outcomes are possible, with highly individualized and comprehensive treatment schedules – individually adjusted and with selected dosage, preparation, host tree, injection site, time schedule of administration, and supplementation with other interventions. This still needs to be investigated. (97, 98)

Currently, several interesting trials have been started: One large publicly funded confirmative (phase III) randomized controlled trial investigating the influence of mistletoe treatment on survival and health-related quality of life in patients with advanced pancreatic cancer, conducted at several cancer centers in Sweden (NCT02948309). One phase I trial on safety of intravenous mistletoe infusions in various cancers, conducted at the John Hopkins Hospital in Baltimore (NCT03051477 [99)), funded by the charity organization Believe Big (www.believebig.org). And one large confirmative (phase III) randomized controlled on the efficacy and safety of intravesical mistletoe extract conpared to Mitomycin instillation in superficial bladder cancer, conducted in more than 30 German study sites. (100)

Clinical application of mistletoe extracts is safe, even in high dosages (6, 7, 101-106).

March 2017

Dr. med. Gunver S. Kienle
IFAEMM Freiburg at the Witten Herdecke University
Center for Complementary Medicine, Medical Center, University of Freiburg

References

  1. Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Browall M, Magri M, Selvekerova S Use of complementary and alternative medicine in cancer patients : a European survey. Ann Oncol 2005; 16(4), pp. 655

  2. Weis J, Bartsch HH, Hennies F, Rietschel M, Heim M, Adam G, G„rtner U, Ammon A Complementary medicine in cancer patients : demand, patients' attitudes and psychological beliefs. Onkologie 1998; 21, pp. 144-149

  3. Petru E, Schmied P, Petru C Komplementäre Maßnahmen bei Patientinnen mit gynäkologischen Malignomen unter Chemo- und Hormontherapie : Bestandsaufnahme und kritische Überlegungen für die Praxis. Geburtshilfe Frauenheilkd 2001; 61, pp. 75-78

  4. Längler A, Spix C, Seifert G, Gottschling S, Graf N, Kaatsch P Complementary and alternative treatment methods in children with cancer : A population-based retrospective survey on the prevalence of use in Germany. Eur J Cancer 2008; 44(15), pp. 2233-2240

  5. Fasching PA, Thiel F, Nicolaisen-Murmann K, Rauh C, Engel J, Lux MP, Beckmann MW, Bani MR Association of complementary methods with quality of life and life satisfaction in patients with gynecologic and breast malignancies. Support Care Cancer 2007; 55(11), pp. 1277-1284

  6. Kienle GS, Kiene H Die Mistel in der Onkologie : Fakten und konzeptionelle Grundlagen. Stuttgart, New York: Schattauer Verlag 2003;

  7. Büssing A Mistletoe. : The Genus Viscum Amsterdam: Hardwood Academic Publishers 2000;

  8. Kienle GS, Kiene H, Albonico HU Anthroposophic Medicine : Effectiveness, Utility, Costs, Safety. Stuttgart, New York: Schattauer Verlag 2006;

  9. Franz H, Ziska P, Kindt A Isolation and properties of three lectins from mistletoe ( Viscum album L.). Biochemical Journal 1981; 195, pp. 481-484

  10. Winterfeld K, Bijnen AB Viscotoxin, ein neuer Inhaltsstoff der Mistel ( Viscum album L.). Liebigs Ann Chem 1948; 561, pp. 107-115

  11. Winterfeld K, Kronenthaler A Zur Chemie des blutdrucksenkenden Bestandteils der Mistel. (Viscum album). Arch Pharm 1942; 280, pp. 103-115

  12. Mueller EA, Anderer FA A Viscum album oligosaccharide activating human natural cytotoxicity is an interferon gamma inducer. Cancer Immunol Immunother 1990; 32, pp. 221-227

  13. Klett CY, Anderer FA Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from Viscum album extract. (2. ed.) Arzneimittel-Forschung/Drug Research 1989; 39(12), pp. 1580-1585

  14. Urech K, Scher JM, Hostanska K, Becker H Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album Journal of Pharmacy and Pharmacology 2005; 57, pp. 101-109

  15. Struh CM, Jager S, Kersten A, Schempp CM, Scheffler A, Martin SF Triterpenoids amplify anti-tumoral effects of mistletoe extracts on murine B16.f10 melanoma in vivo. PLoS One 2013; 8(4), pp. e62168

  16. Struh CM, Jager S, Schempp CM, Scheffler A, Martin SF A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells. Phytother Res 2012; 26(10), pp. 1507-1512

  17. 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), pp. 176-187

  18. 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), pp. 26

  19. Twardziok M, Kleinsimon S, Rolff J, Jager S, Eggert A, Seifert G, Delebinski CI Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma. PLoS One 2016; 11(9), pp. e0159749

  20. Büssing A Induction of apoptosis by the mistletoe lectins : a review on the mechanisms of cytotoxicity mediated by Viscum album L. Apoptosis 1996; (1), pp. 25-32

  21. Büssing A, Vervecken W, Wagner M, Wagner B, Pf ller U, Schietzel M Expression of mitochondrial Apo2.7 molecules and Caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry 1999; 37(2), pp. 133-139

  22. Janssen O, Scheffler A, Kabelitz D In vitro effects of mistletoe extracts and mistletoe lectins. : Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). (2. ed.) Arzneimittel-Forschung/Drug Research 1993; 43(11), pp. 1221-1227

  23. Büssing A, Schaller G, Pfüller U Generation of reactive oxygen intermediates (ROI) by the thionins from Viscum album L.. Anticancer Res 1998; 8, pp. 4291-4296

  24. Podlech O, Harter PN, Mittelbronn M, Poschel S, Naumann U Fermented mistletoe extract as a multimodal antitumoral agent in gliomas. Evid Based Complement Alternat Med 2012; pp. 501796

  25. Elluru SR, Van Huyen JPD, Delignat S, Prost F, Heudes D, Kazatchkine MD, Friboulet A, Kaveri SV Antiangiogenic properties of Viscum album extracts are associated with endothelial cytotoxicity. Anticancer Res 2009; 29(8), pp. 2945

  26. Büssing A, Azhari T, Ostendorp K, Lehnert A, Schweizer K Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. Eur J Cancer 1994; 30(12), pp. 1836-1841

  27. Büssing A, Jungmann H, Suzart K, Schweizer K Suppression of sister chromatid exchange-inducing DNA lesions in cultured peripheral blood mononuclear cells by Viscum album L. J Exp Clin Cancer Res 1996; 15, pp. 107-114

  28. Büssing A, Regnery A, Schweizer K Effects of Viscum album L. on cyclophosphamide-treated peripheral blood mononuclear cells in vitro : sister chromatid exchanges and activation/proliferation marker expression. Cancer Letters 1995; 94, pp. 199-205

  29. Kovacs E, Hajto T, Hostanska K Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador). Eur J Cancer 1991; 27(12), pp. 1672-1676

  30. Kienle GS, Glockmann A, Schink M, Kiene H Viscum album L. extracts in breast and gynaecologic cancers : A systematic review of clinical and preclinical research. J Exp Clin Cancer Res 2009; 28(79),
    doi:10.1186/1756-9966-1128-1179

  31. Gaafar R, Rahman A, Aboulkasem F, El Bastawisy A Mistletoe preparation (Viscum Fraxini-2) as palliative treatment for malignant pleural effusion : a feasibility study with comparison to bleomycin. Ecancermedicalscience 2014; 8, pp. 424

  32. Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer : a randomised clinical trial on overall survival. Eur J Cancer 2013; 49(18), pp. 3788-3797

  33. Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe-a randomized controlled trial. Dtsch Arztebl Int 2014; 111(28), pp. 493-502

  34. Bar-Sela G, Wollner M, Hammer L, Agbarya A, Dudnik E, Haim N 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 2013; 49(5), pp. 1058-1064

  35. Grah C Misteltherapie bei nichtkleinzelligem Bronchialkarzinom. Randomisierte, offene Phase-II- Studie zur Untersuchung der Verträglichkeit und Wirksamkeit von Viscum-album-Extrakt in der palliativen, additiven Behandlung des fortgeschrittenen nichtkleinzelligen Berlin: GKH Havelhöhe, Akademisches Lehrkrankenhaus der medizinischen Fakultät der Charité, Universitätsmedizin Berlin 2010;

  36. Grah C, Matthes B, Happel H, Lemmens HP Randomisierte, offene Phase-II-Studie zur Untersuchung von Viscum album-Extrakt in der palliativen, additiven Behandlung des fortgeschrittenen nichtkleinzelligen Bronchialkarzinoms (NSCLC). Essen: KVC Verlag Die Mistel in der Tumortherapie 3 Aktueller Stand der Forschung und klinische Anwendung. 2013; pp. 389-401
    edn. Edited by Scheer R, Alban S, Becker H, Blaschek W, Kreis W, Matthes H, Schilcher H, Stange R.

  37. Longhi A, Reif M, Mariani E, Ferrari S A Randomized Study on Postrelapse Disease-Free Survival with Adjuvant Mistletoe versus Oral Etoposide in Osteosarcoma Patients. Evid Based Complement Alternat Med 2014; pp. 210198

  38. Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma : a randomized, controlled pilot study. BMC Complement Altern Med 2012; 12(1), pp. 172

  39. Grossarth-Maticek R, Ziegler R. Kontrollierte Studien zur präventiven Misteltherapie bei Myomen, Endometriosen und Cervix Dysplasie. Essen: KVC Verlag Die Mistel in der Tumortherapie 2 - Aktueller Stand der Forschung und klinische Anwendung. edn. Edited by Scheer R, Alban S, Becker H, Holzgrabe U, Kemper FH, Kreis W, Matthes H, Schilcher F. 2009; pp. 537-550

  40. Hekal IA, Samer T, Ibrahim EI Viscum Fraxini 2, as an adjuvant therapy after resection of superficial bladder cancer : Prospective clinical randomized study. Abstract P8. In. 2009; pp. 120

  41. Tröger W, Jezdic S, Zdrale Z, Tisma N, Hamre HJ, Matijasevic M 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 and Clinical Research 2009; 3, pp. 35-45

  42. Tröger W, Matijasevic M, Zdrale Z, Tisma N, Jezdic S Additional therapy with mistletoe extracts in breast cancer patients receiving chemotherapy : a prospective randomized open label pilot study. Essen: KVC Verlag Die Mistel in der Tumortherapie 2 - Aktueller Stand der Forschung und klinische Anwendung. edn. Edited by Scheer R, Alban S, Becker H, Holzgrabe U, Kemper FH, Kreis W, Matthes H, Schilcher H. 2009; pp. 509-521

  43. Tröger W, Zdrale Z, Stankovic N, Matijass¡evic M 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 and Clinical Research 2012; 6, pp. 173

  44. Tröger W, Zdrale Z, Tisma N, Matijasevic M Additional therapy with a mistletoe product during adjuvant chemotherapy ofbreast cancer patients improves quality of life. Evidence Based Complementary and Alternative Medicine 2014;
    In press.


  45. Büssing A, Brückner U, Enser-Weis U, Schnelle M, Schumann A, Schietzel M, Hatzmann W, Hackmann J Modulation of chemotherapy-associated immunosuppression by intravenous application of Viscum album L. extract (Iscador) : a randomised phase II study. . Eur J Integr Med 2008; 1, pp. S44-S45

  46. Grossarth-Maticek R, Ziegler R 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 2008; 13, pp. 107-120

  47. Grossarth-Maticek R, Ziegler R Prospective controlled cohort studies on long-term therapy of ovarian cancer patients with mistletoe ( Viscum album L.) extracts Iscador. Arzneimittel-Forschung/Drug Research 2007; 57(10), pp. 665-678

  48. Grossarth-Maticek R, Ziegler R Wirksamkeit und Unbedenklichkeit einer Langzeitbehandlung von Melanompatienten mit einem Mistelpräparat (Iscador© ) Schweizerische Zeitschrift für Ganzheitsmedizin 2007; 19, pp. 325-332

  49. Grossarth-Maticek R, Ziegler R Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador©) Forsch Komplementarmed Klass Naturheilkd 2007; 14, pp. 140-147

  50. Schink M, Tröger W, Dabidian A, Goyert A, Scheuerecker H, Meyer J, Fischer IU, Glaser F Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. : A randomized phase III trial. Forsch Komplementarmed Klass Naturheilkd 2007; 14(1), pp. 9-17

  51. Grossarth-Maticek R, Ziegler R Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador). Forsch Komplementarmed Klass Naturheilkd 2006; 13, pp. 285-292

  52. Grossarth-Maticek R, Ziegler R Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador) Supplementary materials. In. 2006;

  53. Auerbach L, Dostal V, Vclavik-Fleck I, Kubista E, Rosenberger A, Rieger S, Tröger W, Schierholz JM Signifikant höherer Anteil aktivierter NK-Zellen durch additive Misteltherapie bei chemotherapierten Mamma-Ca-Patientinnen in einer prospektiven randomisierten doppelblinden Studie. Essen: KVC Verlag Fortschritte in der Misteltherapie Aktueller Stand der Forschung und klinischen Anwendung. edn. Edited by Scheer R, Bauer R, Becker H, Fintelmann V, Kemper FH, Schilcher H. 2005; pp. 543-554

  54. Enesel MB, Acalovschi I, Grosu V, Sbarcea A, Rusu C, Dobre A, Weiss T, Zarkovic K Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients. Anticancer Res 2005; 25, pp. 4583-4590

  55. Eggermont A, Kleeberg UR, Ruiter DJ, Suciu S European Organization for Research and Treatment of Cancer Melanoma Group trial experience with more than 2,000 patients, evaluating adjuvant treatment with low or intermediate doses of interferon alpha-2b. American Society of Clinical Oncology Educational Book. edn. Edited by American Society of Clinical O. Baltimore, MD: Lippincott Williams & Wilkins 2001; pp. 88-93

  56. Kleeberg UR, Suciu S, Brücker EB, Ruiter DJ, Chartier C, Li‚nard D, Marsden J, Schadendorf D, Eggermont AMM Final results of the EORTC 18871/DKG 80-1 randomised phase III trial: rIFN-à2b versus rIFN- g versus Iscador M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3mm) or regional lymph node metastasis. Eur J Cancer 2004; 40, pp. 390-402

  57. Piao BK, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS 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 2004; 24(1), pp. 303-309

  58. Cazacu M, Oniu T, Lungoci C, Mihailov A, Cipak A, Klinger R, Weiss T, Zarkovic N The influence of Isorel on the advanced colorectal cancer. Cancer Biotherapy & Radiopharmaceuticals 2003; 18(1), pp. 27-34

  59. Borrelli E Evaluation of the quality of life in breast cancer patients undergoing lectin standardized mistletoe therapy. Minerva Medica 2001; 92(1), pp. 105-107

  60. Grossarth-Maticek R, Kiene H, Baumgartner S, Ziegler R 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. Alternative Therapies in Health and Medicine 2001; 7(3), pp. 57-78

  61. Kim MH, Park YK, Lee SH, Kim SC, Lee SY, Kim CH, Kim YK, Kim KH, Moon HS, Song JS et al Comparative study on the effects of a Viscum album (L.) extract (mistletoe) and doxycycline for pleurodesis in patients with malignant pleural effusion. : 51th Meeting of The Korean Association of Internal Medicine. Translation by Helixor Heilmittel GmbH. Korean Journal of Medicine 1999; 57(2), pp. S121

  62. Dold U, Edler L, Mäurer H C, Müller-Wening D, Sakellariou B, Trendelenburg F, Wagner G Krebszusatztherapie beim fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom. Stuttgart, New York: Georg Thieme Verlag 1991;

  63. Salzer G, Danmayr E, Wutzlhofer F, Frey S Adjuvante Iscador-Behandlung operierter nicht kleinzelliger Bronchuskarzinome. Dtsch Z Onkol 1991; 23(4), pp. 93-98

  64. Gutsch J, Berger H, Scholz G, Denck H Prospektive Studie beim radikal operierten Mammakarzinom mit Polychemotherapie, Helixor und unbehandelter Kontrolle. Dtsch Z Onkol 1988; (4), pp. 94-100

  65. Salzer G 30 Jahre Erfahrung mit der Misteltherapie an Öffentlichen Krankenanstalten. Stuttgart: Verlag Freies Geistesleben Misteltherapie Eine Antwort auf die Herausforderung Krebs. edn. Edited by Leroi R. 1987; pp. 173-215

  66. Douwes FR, Wolfrum DI, Migeod F Ergebnisse einer prospektiv randomisierten Studie : Chemotherapie versus Chemotherapie plus "Biological Response Modifier" bei metastasierendem kolorektalen Karzinom. Krebsgeschehen 1986; 18(6), pp. 155-163

  67. Lange O, Scholz G, Gutsch J Modulation der subjektiven und objektiven Toxizität einer aggressiven Chemotherapie mit Helixor. Unpublished Report. In. 1985;

  68. Salzer G, Havelec L Adjuvante Iscador-Behandlung nach operiertem Magenkarzinom : Ergebnisse einer randomisierten Studie. Krebsgeschehen 1983; 15(4), pp. 106-110

  69. Salzer G Prospektiv randomisierte Studie : Operiertes Magenkarzinom - Adjuvante Behandlung mit Iscador. Dtsch Z Onkol 1988; 20(4), pp. 90-93

  70. Salzer G, Denck H Randomisierte Studie über medikamentöse Rezidivprophylaxe mit 5-Fluorouracil und Iscador beim resezierten Magenkarzinom : Ergebnisse einer Zwischenauswertung. Krebsgeschehen 1979; 11(5), pp. 130-131

  71. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, Scholz M, Neiá A, Strutz J, Hennig M, Lenartz T, Arnold W The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients : a randomised controlled clinical trial. Eur J Cancer 2001; 37, pp. 23-31

  72. Heiny BM dditive Therapie mit standardisiertem Mistelextrakt reduziert die Leukopenie und verbessert die Lebensqualität von Patientinnen mit fortgeschrittenem Mammakarzinom unter palliativer Chemotherapie (VEC-Schema). Krebsmedizin 1991; 12, pp. 1-14
    Sonderdruck

  73. Heiny BM, Albrecht V Komplementäre Therapie mit Mistellektin-1-normiertem Extrakt : Lebensqualitätsstabilisierung beim fortgeschrittenen kolorektalen Karzinom - Fakt oder Fiktion? Die Medizinische Welt 1997; 48, pp. 419-423

  74. Lenartz D, Dott U, Menzel J, Schierholz JM, Beuth J Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 2000; 20, pp. 2073-2076

  75. Lenartz D, Stoffel B, Menzel J, Beuth J Immunoprotective activity of the galactoside-specific lectin from Mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 1996; 16, pp. 3799-3802

  76. Brinkmann OA, Lümmen G, Luboldt HJ, Hertle L, Rübben H Interferon à, interleukin 2 and 5-flourouracil compared with mistletoe lectin in metastatic renal cell carcinoma (MRCC). European Urology 2000; 37(2), pp. 152

  77. Lümmen G, Brinkmann OA, Luboldt HJ, Hertle L, Rübben H Interferon-a, interleukin-2 and 5-fluorouracil versus mistletoe lectin in metastatic renal cell carcinoma : Long-term results. European Urology 2001; 39(5), pp. 121

  78. Goebell PJ, Otto T, Suhr J, Rübben H Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer : a randomized phase II trial. The Journal of Urology 2002; 168, pp. 72-75

  79. Semiglasov VF, Stepula VV, Dudov A, Lehmacher W, Mengs U 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. Res 2004 w/o y.; 24, pp. 1293-1302

  80. Semiglasov VF, Stepula VV, Dudov A, Schnitker J, Mengs U 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 2006; 26, pp. 1519-1530

  81. Kienle GS, Kiene H 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 2010; 9(2), pp. 142-157

  82. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M Mistletoe therapy in oncology. Cochrane DatabaseSyst Rev 2008; (2), pp. CD003297

  83. Kienle GS, Berrino F, Büssing A, Portalupi E, Rosenzweig S, Kiene H Mistletoe in cancer : a systematic review on controlled clinical trials. Med Res 2003; 8, pp. 109-119

  84. Kienle GS, Kiene H Complementary cancer therapy : a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. EurJ Med Res 2007; 12(3), pp. 103-119

  85. Kienle GS, Glockmann A, Grugel R, Hamre HJ, Kiene H Clinical research on anthroposophic medicine : update of a health technology assessment report and status quo. Forsch Komplementarmed Klass Naturheilkd 2011; 18(5), pp. 269-282

  86. Mabed M, El-Helw L, Sharma S Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. Br J Cancer 2004; 90, pp. 65-69

  87. Mahfouz MM, Ghaleb HA, Zawawy A, Scheffler A Significant tumor reduction, improvement of pain and quality of life and normalization of sleeping patterns of cancer patients treated with a high dose of mistletoe. Ann Oncol 1998; 9, pp. 129

  88. Mahfouz MM, Ghaleb HA, Hamza MR, Fares L, Moussa L, Moustafua A, El-Za Wawy A, Kourashy L, Mobarak L, Saed S et al Multicenter open labeled clinical study in advanced breast cancer patients : A preliminary report. Journal of the Egyptian NatCancer Inst 1999; 11(3), pp. 221-227

  89. Seifert G, Tautz C, Seeger K, Henze G, Laengler A Therapeutic use of mistletoe for CD30+ cutaneous lymphoproliferative disorder / lymphomatoid papulosis. J Eur Acad Dermatol Venereol 2006; 21, pp. 1-2

  90. Werthmann PG, Helling D, Heusser P, Kienle GS Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma. BMJ Case Reports 2014;
    doi: 10.1136/bcr-2013-203180

  91. Werthmann PG, Sträter G, Friesland H, Kienle GS Durable Response of Cutaneous Squamous Cell Carcinoma Following High-dose Peri-lesional Injections of Viscum album Extracts : A Case Report. Phytomedicine 2013; 20, pp. 324-327

  92. Orange M, Fonseca M, Lace A, von Laue HB, Geider S Durable tumour responses following primary high-dose induction with mistletoe extracts : Two case reports. Eur J Integr Med 2010; 2, pp. 63-69

  93. Orange M, Lace A, Fonseca M, von Laue HB, Geider S, Kienle GS Durable Regression of Primary Cutaneous B-cell Lymphoma following Fever-inducing Mistletoe Treatment : Two Case Reports. Glob Adv Health Med 2012; 1(1), pp. 16-23

  94. von Schoen-Angerer T, Wilkens J, Kienle GS, Kiene H, Vagedes J High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer : A Retrospective Case Series. Perm J 2015; 19(4), pp. 76-83

  95. Kirsch A Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M). J Altern Complement Med 2007; 13(4), pp. 443-445

  96. Rose A, El-Leithy T, vom Dorp F, Zakaria A, Eisenhardt A, Tschirdewahn S, Rubben H Mistletoe Plant Extract in Patients with Nonmuscle Invasive Bladder Cancer : Results of a Phase Ib/IIa Single Group Dose Escalation Study. J Urol 2015; 194(4), pp. 939-943

  97. Kienle GS, Mussler M, Fuchs D, Kiene H Intravenous Mistletoe Treatment in Integrative Cancer Care : A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors. Evid Based Complement Alternat Med 2016; pp. 4628287

  98. Kienle GS, Mussler M, Fuchs D, Kiene H Individualized Integrative Cancer Care in Anthroposophic Medicine : A Qualitative Study of the Concepts and Procedures of Expert Doctors. Integr Cancer Ther 2016;

  99. Sugarman J Are mistletoe extract injections the next big thing in cancer therapy? ohns Hopkins Magazine 2014;

  100. Rexer H, Geschaftsstelle der AUO Study on the treatment of nonmuscle invasive bladder cancer : A phase III efficacy study for intravesical instillation of mistletoe extract in superficial bladder cancer (TIM) AB 40/11 of the AUO. Urologe A 2015; 54(3), pp. 406-408

  101. Kienle GS, Grugel R, Kiene H Safety of higher dosages of Viscum album L. in animals and humans : systematic review of immune changes and safety parameters. BMC Complement Altern Med 2011; 11(1), pp. 72

  102. Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients. EvidBased Complement AlternatMed 2014; pp. 724258

  103. Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology. Integr Cancer Ther 2015; 14(2), pp. 140-148

  104. Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology : An Observational Study. Evid Based Complement Alternat Med 2014; pp. 236310

  105. Stein GM, Pfüller U, Schietzel M, Büssing A Toxic proteins from European mistletoe (Viscum album L. ) : increase of intracellular IL-4 but decrease of IFN- g in apoptic cells. Anticancer Res 2000; 20, pp. 1673-1678

  106. Stein GM, Berg PA Adverse effects during therapy with mistletoe extracts. Amsterdam: Hardwood Academic Publishers Mistletoe The Genus Viscum edn. Edited by Büssing A. 2000; pp. 195-208


Exemplary literature

Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe – a randomized controlled trial. Dtsch Arztebl Int 2014, 111:493-502
http://www.aerzteblatt.de/pdf.asp?id=161151

Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer 2013, 49:3788-3797
http://www.ejcancer.com/article/S0959-8049%2813%2900550-9/pdf

Mansky PJ, Wallerstedt DB, Sannes TS, Stagl J, Johnson LL, Blackman MR, Grem JL, Swain SM, Monahan BP: NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors. Evidence-Based Complementary and Alternative Medicine 2013, 2013: 964592
http://www.hindawi.com/journals/ecam/2013/964592

Mabed M, El-Helw L, Sharma S: Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. Br J Cancer 2004, 90:65-69
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395314/

Piao BK, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS: 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 2004, 24:303-309
https://www.researchgate.net/publication/5390410_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

Semiglasov VF, Stepula VV, Dudov A, Schnitker J, Mengs U: 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 2006, 26:1519-1530
http://ar.iiarjournals.org/content/26/2B/1519.full.pdf

Kienle GS, Grugel R, Kiene H: Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters.BMC Complement Altern Med 2011, 11:72
http://www.biomedcentral.com/content/pdf/1472-6882-11-72.pdf

Kienle GS, Glockmann A, Schink M, Kiene H: Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. Journal of Experimental & Clinical Cancer Research: CR 2009, 28:79
http://www.biomedcentral.com/content/pdf/1756-9966-28-79.pdf

Kienle GS, Kiene H:Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res 2007, 12:103-119
http://www.daig-net.de/site-content/die-daig/fachorgan/2007-1/ejomr-2007_3-pdfs/S.103_Kienle.pdf

Kienle GS, Kiene H: 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 2010, 9:142-157
http://ict.sagepub.com/content/9/2/142.long