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

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.

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study.

Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this "off-label" application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs) to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6%) reported 32 ADRs of mild (59.4%) or moderate severity (40.6%). No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%), versus prior to chemotherapy (1.6%). ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients.

Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5 cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe.

Intratumoral Mistletoe (Viscum album L) Therapy in Patients With Unresectable Pancreas Carcinoma: A Retrospective Analysis.

Pancreatic carcinoma remains one of the main causes for cancer-related death. Intratumoral application of anticancer agents is discussed as a promising method for solid tumors such as pancreatic cancer. Endoscopic ultrasound provides a good tool to examine and treat the pancreas. European mistletoe (Viscum album L) is a phytotherapeutic commonly used in integrative oncology in Central Europe. Its complementary use seeks to induce immunostimulation and antitumoral effects as well as alleviate chemotherapeutic side effects. Intratumoral mistletoe application has induced local tumor response in various cancer entities. This off-label use needs to be validated carefully in terms of safety and benefits. Here we report on 39 patients with advanced, inoperable pancreatic cancer, who received in total 223 intratumoral applications of mistletoe, endoscopic ultrasound guided or under transabdominal ultrasound control. No severe procedure-related events were reported. Adverse drug reactions were mainly increased body temperature or fever in 14% and 11% of the applications, respectively. Other adverse drug reactions, such as pain or nausea, occurred in less than 7% of the procedures. No severe adverse drug reaction was recorded. Patients received standard first- and second-line chemotherapy and underwent adequate palliative surgical interventions as well as additive subcutaneous and partly intravenous mistletoe application. A median survival of 11 months was observed for all patients, or 11.8 and 8.3 months for stages III and IV, respectively. Due to the multimodal therapeutic setting and the lack of a control group, the effect of intratumoral mistletoe administration alone remains unclear. This retrospective analysis suggests that intratumoral-applicated mistletoe might contribute to improve survival of patients with pancreatic cancer. In conclusion, the application is feasible and safe, and its efficacy should be evaluated in a randomized controlled trial.

Network Oncology (NO)--a clinical cancer register for health services research and the evaluation of integrative therapeutic interventions in anthroposophic medicine.

BACKGROUND: Concepts of integrative oncology (IO), as have been offered by anthroposophic medicine (AM) for decades, are gaining increasing interest and acceptance. Central aspects are multimodal therapeutic interventions, health-related quality of live, and patients' preference as well as therapeutic relationship and clinical outcome. Despite its broad application, IO lacks evaluation in clinical practice and complementary therapies are not monitored by any cancer registries. METHODS: To close this gap we established 'Network Oncology' (NO), a conjoint registry of German outpatient AM practitioners and AM hospitals. In this paper we present the project and a first data overview and compare it to epidemiological registers and current literature. RESULTS: NO has collected 10,405 cancer patients' records in 6 years. Compared to epidemiological registers our data show minor differences in disease entity distribution, age, and gender. There is an overproportional amount of young breast cancer patients in NO institutions indicating a demand for integrative therapies in this group. There is no difference between the UICC (Union for International Cancer Control) stages at first diagnosis and at admission to a NO facility. According to our data conventional therapies were less frequently administered after admission to a NO facility. Nevertheless, one third of the patients received their first conventional therapy in a NO facility. 80% of the patients received mistletoe preparations and 63% had nonpharmacotherapeutic, complementary interventions. CONCLUSION: Integrative oncological approaches attract a great number of patients visiting AM institutions. The NO provides an infrastructure to evaluate integrative interventions in AM, allows comparison to other clinical registers, and thus can contribute to health service research in this field.