Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in oncology

Integrative Cancer Therapies

Volumn 14, Issue 2, 2015, Pages 140-148

  Steele, Megan L ^a   Axtner, Jan ^a   Happe, Antje ^a   Kröz, Matthias ^a,c,d   Matthes, Harald ^a,b   Schad, Friedemann ^a,b  

^a Havelhoehe Research Institute   (Germany)

^b Hospital Gemeinschaftskrankenhaus Havelhoehe   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d UNIVERSITY OF WITTEN HERDECKE   (Germany)

Author keywords

adverse drug reactions; adverse events; Anthroposophic Medicine; cancer; intratumoral; mistletoe; safety; Viscum album

Indexed keywords

ENALAPRIL; GLYCERYL TRINITRATE; METOPROLOL; PIRITRAMIDE; TRAMADOL; VISCUM ALBUM EXTRACT; ANTINEOPLASTIC AGENT; PLANT EXTRACT;

ABDOMINAL DISCOMFORT; ABDOMINAL PAIN; ADULT; AGED; ANALGESIA; ANTIHYPERTENSIVE THERAPY; ARTICLE; BODY TEMPERATURE; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PAIN; CANCER PATIENT; CANCER REGISTRY; CLINICAL PRACTICE; COLORECTAL CANCER; DRUG DOSAGE FORM COMPARISON; DRUG INDUCED HEADACHE; DYSPHAGIA; DYSPNEA; ERYTHEMA; FEMALE; FEVER; GASTROINTESTINAL PAIN; HOT FLUSH; HUMAN; HYPERSALIVATION; HYPERTENSION; HYPOTENSION; IMMUNOPATHOLOGY; LIVER CANCER; LUNG CANCER; LYMPHOCYTOSIS; MAJOR CLINICAL STUDY; MALE; NAUSEA; OFF LABEL DRUG USE; PANCREAS CANCER; PATIENT SAFETY; PRIORITY JOURNAL; RETCHING; SIDE EFFECT; TONGUE SWELLING; VISCUM ALBUM; VOMITING; CHEMISTRY; CLINICAL TRIAL; COMPARATIVE STUDY; GERMANY; INJECTION; MIDDLE AGED; MULTICENTER STUDY; NEOPLASMS; PATHOLOGY; REGISTER; RETROSPECTIVE STUDY; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS, PHYTOGENIC; FEMALE; GERMANY; HUMANS; INJECTIONS; MALE; MIDDLE AGED; NEOPLASMS; OFF-LABEL USE; PLANT EXTRACTS; REGISTRIES; RETROSPECTIVE STUDIES; VISCUM ALBUM;

EID: 84922858558     PISSN: 15347354     EISSN: 1552695X     Source Type: Journal    
DOI: 10.1177/1534735414563977     Document Type: Article

References (62)

1. Yan BM, Van Dam J. Endoscopic ultrasound-guided intratumoural therapy for pancreatic cancer. Can J Gastroenterol. 2008 ; 22: 405-410
2. Baird JR, Byrne KT, Lizotte PH, et al. Immune-mediated regression of established B16F10 melanoma by intratumoral injection of attenuated Toxoplasma gondii protects against rechallenge. J Immunol. 2013 ; 190: 469-478
3. Nokisalmi P, Pesonen S, Escutenaire S, et al. Oncolytic adenovirus ICOVIR-7 in patients with advanced and refractory solid tumors. Clin Cancer Res. 2010 ; 16: 3035-3043
4. Hohenforst-Schmidt W, Zarogoulidis P, Darwiche K, et al. Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies. Drug Des Devel Ther. 2013 ; 7: 571-583
5. Kumar V, Ramaswami N, Pandey A, et al. Clinico-immunological response to intratumoral versus intravenous neoadjuvant chemotherapy in advanced pediatric solid malignancies. Indian J Med Paediatr Oncol. 2013 ; 34: 80-84
6. Pesonen S, Diaconu I, Kangasniemi L, et al. Oncolytic immunotherapy of advanced solid tumors with a CD40L-expressing replicating adenovirus: assessment of safety and immunologic responses in patients. Cancer Res. 2012 ; 72: 1621-1631
7. Whalen GF, Sullivan M, Piperdi B, Wasseff W, Galili U. Cancer immunotherapy by intratumoral injection of alpha-gal glycolipids. Anticancer Res. 2012 ; 32: 3861-3868
8. van Schalkwyk MC, Papa SE, Jeannon JP, Guerrero Urbano T, Spicer JF, Maher J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev. 2013 ; 24: 134-142
9. Jackaman C, Lew AM, Zhan Y, et al. Deliberately provoking local inflammation drives tumors to become their own protective vaccine site. Int Immunol. 2008 ; 20: 1467-1479
10. Fillat C, Jose A, Bofill-Deros X, Mato-Berciano A, Maliandi MV, Sobrevals L. Pancreatic cancer gene therapy: from molecular targets to delivery systems. Cancers. 2011 ; 3: 368-395
11. Baliaka A, Zarogoulidis P, Domvri K, et al. Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53. GeneTher. 2014 ; 21: 158-167
12. Yang L, Wang B, Qiao W, Liu P. A novel combination chemotherapy integrating with intratumoral chemotherapy. Med Hypotheses. 2009 ; 73: 334-335
13. Hermiston T. A demand for next-generation oncolytic adenoviruses. Curr Opin Mol Ther. 2006 ; 8: 322-330
14. Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med. 2000 ; 6: 879-885
15. Hecht JR, Farrell JJ, Senzer N, et al. EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: a phase I/II study. Gastrointest Endosc. 2012 ; 75: 332-338
16. Vacchelli E, Eggermont A, Sautes-Fridman C, et al. Trial watch: oncolytic viruses for cancer therapy. Oncoimmunology. 2013 ; 2: e24612
17. Dias JD, Guse K, Nokisalmi P, et al. Multimodal approach using oncolytic adenovirus, cetuximab, chemotherapy and radiotherapy in HNSCC low passage tumour cell cultures. Eur J Cancer. 2010 ; 46: 625-635
18. Gajewski TF, Meng Y, Blank C, et al. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev. 2006 ; 213: 131-145
19. Harmsma M, Gromme M, Ummelen M, Dignef W, Tusenius KJ, Ramaekers FC. Differential effects of Viscum album extract IscadorQu on cell cycle progression and apoptosis in cancer cells. Int J Oncol. 2004 ; 25: 1521-1529
20. Seifert G, Jesse P, Laengler A, et al. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Lett. 2008 ; 264: 218-228
21. Delebinski CI, Jaeger S, Kemnitz-Hassanin K, Henze G, Lode HN, Seifert GJ. A new development of triterpene acid-containing extracts from displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Viscum album Cell Prolif. 2012 ; 45: 176-187
22. Zarkovic N, Vukovic T, Loncaric I, et al. An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm. 2001 ; 16: 55-62
23. Eisenbraun J, Scheer R, Kröz M, Schad F, Huber R. Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract. Phytomedicine. 2011 ; 18: 151-157
24. Beuth J, Schneider B, Schierholz JM. Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study. Anticancer Res. 2008 ; 28: 523-527
25. Beuth J, Ko HL, Schneider H, et al. Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model. Anticancer Res. 2006 ; 26: 4451-4456
26. Rostock M, Huber R, Greiner T, et al. Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts. Anticancer Res. 2005 ; 25: 1969-1975
27. Bussing A, Schietzel M. Apoptosis-inducing properties of Viscum album L. extracts from different host trees, correlate with their content of toxic mistletoe lectins. Anticancer Res. 1999 ; 19: 23-28
28. 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 ; 2012: 501796
29. Christen-Clottu O, Klocke P, Burger D, Straub R, Gerber V. Treatment of clinically diagnosed equine sarcoid with a mistletoe extract (Viscum album austriacus). J Vet Intern Med. 2010 ; 24: 1483-1489
30. Orange M, Fonseca M, Lace A, von Laue H, Geider S. Durable tumour responses following primary high dose induction with mistletoe extracts: two case reports. Eur J Integr Med. 2010 ; 2: 63-69
31. Werthmann PG, Strater 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: 324-327
32. Ritter PR, Tischoff I, Uhl W, Schmidt WE, Meier JJ. Sustained partial remission of metastatic pancreatic cancer following systemic chemotherapy with gemcitabine and oxaliplatin plus adjunctive treatment with mistletoe extract. Onkologie. 2010 ; 33: 617-619
33. Orange M, Lace A, Fonseca MP, von Laue BH, 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: 18-25
34. Schad F, Axtner J, Buchwald D, et al. Intratumoral mistletoe (Viscum album L) therapy in patients with unresectable pancreas carcinoma: a retrospective analysis. Integr Cancer Ther. 2013 ; 13: 332-340
35. Schad F, Axtner J, Happe A, et al. Network Oncology (NO): a clinical cancer register for health services research and the evaluation of integrative therapeutic interventions in anthroposophic medicine. Forsch Komplementmed. 2013 ; 20: 369-375
36. Steele ML, Axtner J, Happe A, Kröz M, Matthes H, Schad F.. Adverse drug reactions and expected effects to therapy with subcutaneous mistletoe extracts (Viscum album L.) in cancer patients. Evid Based Complement Alternat Med. 2014 ; 2014: 724258
37. Steele ML, Axtner J, Happe A, Kröz 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. In press ;:
38. Schad F, Teodoridis C, Albrecht U, et al. Network Oncology (NO): a European approach to health service research on cancer treatment with focus on concurrent use of complementary therapies. Eur J Integr Med. 2008 ; 1: 12-13
39. Schad F, Pissarek J, Jeschke E, Albrecht U, Matthes H. QuaDoSta (Quality Assurance, Documentation and Statistics): a flexible, platform-independent, open source database for oncological documentation. Cancer Res Clin Oncol. 2004 ; 130: 785
40. R Core Team ; 2012 :
41. International Conference on Harmonization. E2D: Post-approval safety data management: definitions and standards for expedited reporting. http://www.ich.org/fileadmin/Public-Web-Site/ICH-Products/Guidelines/Efficacy/E2D/Step4/E2D-Guideline.pdf.
42. Medical Dictionary for Regulatory Activites (MedDRA). MedDRA Hierarchy. http://www.meddra.org/how-to-use/basics/hierarchy.
43. CTEP. Common terminology criteria for adverse events. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE-4.03-2010-06-14-QuickReference-5x7.pdf.
44. Mansky PJ, Wallerstedt DB, Sannes TS, et al. NCCAM/NCI phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors. Evid Based Complement Alternat Med. 2013 ; 2013: 964592
45. Orange M Mistletoe Therapy for Cancer Patients. Birmingham, UK: University of Birmingham ; 2010 :
46. Grah C, Matthes B, Griff S, Szymanski S, Mairinger T Die Mistel in der Tumortherapie 2. Aktueller Stand der Forschung und klinischen Anwendung. Scheer R Alban S Becker H Holzgrabe U Kemper FH Kreis W, ed. Essen, Germany: KVC Verlag ; 2009 :
47. Hoessli DC, Ahmad I. Mistletoe lectins: carbohydrate-specific apoptosis inducers and immunomodulators. Curr Org Chem. 2008 ; 12: 918-925
48. Bergmann L, Aamdal S, Marreaud S, Lacombe D, Herold M, Yamaguchi T, Wilhelm-Ogunbiyi K, Lentzen H, Zwierzina H. Phase I trial of r viscumin (INN: aviscumine) given subcutaneously in patients with advanced cancer: A study of the European Organisation for Research and Treatment of Cancer (EORTC protocol number 13001). Eur J Cancer. 2008 ; 44: 1657-1662
49. Petkov V. Plants and hypotensive, antiatheromatous and coronarodilatating action. Am J Chin Med. 1979 ; 7: 197-236
50. Ofem OE, Eno AE, Imoru J, Nkanu E, Unoh F, Ibu JO. Effect of crude aqueous leaf extract of Viscum album (mistletoe) in hypertensive rats. Am J Chin Med. 2007 ; 39 (1). 15-19
51. Poruthukaren KJ, Palatty PL, Baliga MS, Suresh S. Clinical evaluation of Viscum album mother tincture as an antihypertensive: a pilot study. J Evid Based Complement Alternat Med. 2014 ; 19: 31-35
52. Abnoba viscum: information for healthcare professionals. http://www.anthromed.org/UploadedDocuments/Abnoba%20Viscum.pdf. Accessed April 9, 2014.
53. Schlodder D. Die HELIXOR: Sortenwahl. Paper presented at: Anthroposophische Onkologie Seminar ; Berlin, Germany ;..
54. Kelter G, Schierholz JM, Fischer IU, Fiebig HH. Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. Anticancer Res. 2007 ; 27: 223-233
55. Orange M, Lace A, von Laue HB. The importance of the primary dosis in mistletoe therapy. Phytomedicine. 2007 ; 14: 29
56. OrangeM. Mistletoe therapy and hyperthermia for cancer: turning up the heat. http://www.positivehealth.com/article/cancer/mistletoe-therapy-and-hyperthermia-for-cancer-turning-up-the-heat. Accessed December 9, 2014.
57. Büssing A, Troger W, Stumpf C, Schietzel M. Local reactions to treatments with extracts and their association with T-lymphocyte subsets and quality of life. Viscum album Anticancer Res. 2008 ; 28: 1893-1897
58. Matthes B, Fritz P, Mürdter TE, Kröz M, von Laue HB, Matthes H Fortschritte in der Misteltherapie. Scheer R Bauer R Becker H Fintelmann V Kemper F Schilcher H, ed. Essen, Germany: KVC Verlag ; 2005 :
59. Delyon J, Mateus C, Lefeuvre D, et al. Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. Ann Oncol. 2013 ; 24: 1697-1703
60. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 ; 357: 2040-2048
61. Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res. 2007 ; 13: 3913-3921
62. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 ; 25: 1960-1966