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. Conclusion. 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.

Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients

“…For all other SOCs, the patient’s proportion was higher in the control group ( Figure 2 ). No serious AEs and serious adverse reactions (ICH) [ 40 ] were documented for the total study cohort. No deaths from study-drug toxic effects were reported.…”

“…Furthermore, add-on VA maintained ICI-induced toxicity profile in patients with advanced and metastasized lung cancer and melanoma [ 36 , 37 ]. Add-on VA therapy has been reported to entail a sound safety profile with no serious side effects [ 35 , 38 , 39 , 40 ]. We hypothesize that addition of VA therapy in the present study would not increase the known side effects of targeted treatment and might even reduce them.…”

Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer

“…With regards to adverse effects the safety profile of VA has indicated that subcutaneous (s.c.) and intravenous (i.v.) applications of VA in cancer were safe with no serious AEs [30][31][32][33]. A meta-analysis of clinical studies that applied VA Iscador preparations concluded that it might have beneficial effects in psychosomatic self-regulation in addition to short-term quality of life-improving effects in cancer patients [34].…”

Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung

“…In der Klinik entspräche dies am ehesten der intratumoralen, intrapleuralen und auch intravesikalen Applikation. Diese Applikationsformen liegen ebenso wie die Infusion außerhalb der arzneimittelrechtlichen Zulassung [31], es liegen aber wissenschaftliche Daten aus klinischen Studien vor [32][33][34][35]. Die intravesikale Instillation von Mistelextrakt mit dem Ziel der Rezidivprophylaxe beim oberflächli-chen Harnblasenkarzinom hatte in ersten Untersuchungen vergleichbare Effekte zur üblicherweise mit dem Immunmodulator BCG (Bacillus Calmette-Guérin) oder dem Zytostatikum Mitomycin erfolgenden Instillationstherapie gezeigt [34] und wird daher z. Zt.…”