title: Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.
abstract: BACKGROUND
  Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed.
  
  
  METHODS
  The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors.
  
  
  RESULTS
  A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively.
  
  
  CONCLUSIONS
  IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended.
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Steele
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Axtner
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Happe
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany Witten/Herdecke University, Herdecke, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kröz
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany Hospital Havelhoehe, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Matthes
authors.affiliation: Research Institute Havelhoehe, Berlin, Germany Hospital Havelhoehe, Berlin, Germany fschad@havelhoehe.de.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Schad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D056687:Off-Label Use; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012042:Registries; D012189:Retrospective Studies; D028182:Viscum album / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Anthroposophic Medicine; Viscum album; adverse drug reactions; adverse events; cancer; intratumoral; mistletoe; safety