Breast cancer and other gynecological tumors

Safety study on combined administration of targeted therapy with mistletoe extracts (Helixor) in breast cancer and other gynecological tumors

A first clinical experience with additive mistletoe therapy (Helixor) to targeted therapy in 242 patients with breast cancer or other gynecologic cancer entities is now available (216). In a Real-World Data study (RWD study) from the Network Oncology Registry, in which one group of patients received only targeted therapies (n=160) and the other additionally mistletoe therapy (n=82), the side effect rate as well as dose reduction adjustments and therapy discontinuations of the targeted therapy including monoclonal antibodies, tyrosine kinase inhibitors, checkpoint inhibitors, CDK4/6 inhibitors or PARP inhibitors were determined in both groups. It was found that the additional mistletoe therapy did not change the side effect rate of the targeted therapy. Furthermore, no adverse events and a trend towards better adherence to targeted therapy were observed in the group receiving the combined therapy (targeted therapy plus mistletoe extracts). This RWD study is the first of its kind to also highlight the safety profile of newer targeted therapy groups such as CDK 4/6 inhibitors as well as PARP inhibitors in combination with mistletoe extracts. Overall, the data indicate that additional mistletoe therapy with Viscum album L. extracts does not alter the safety profile of targeted therapy in breast cancer and other gynecologic tumors. Further studies involving combined therapy in additional tumor entities are planned.


Chylous ascites ssociated with pancreatic duodenectomy

Sclerotherapy of chylous ascites associated with pancreatic duodenectomy by intraperitoneally injected Viscum album L.

A 56-year-old female patient with diabetes mellitus, chronic B-virus hepatitis, and subclinical hypothyroidism was diagnosed with a well-differentiated, resectable adenocarcinoma in the pancreatic head and so-called at ampulla of Vater (317). After robot-assisted pylorus-preserving pancreatic head resection, the pathologic findings of the tumor (2.2 x 1.8 cm) revealed a moderately differentiated infiltrating adenocarcinoma of the pancreas with lymphatic and perineural invasion. After surgery, the patient recovered well and was discharged. On day 19 after surgery, the patient was re-admitted to the hospital for chylous ascites as a result of a surgically induced lymphatic vessel injury. During the course of the examinations, the drainage fluid had a milky straw color with a serum ascites albumin ratio of 1.3 g/dL. Ascitic drainage, albumin substitution, and the administration of diuretics and lipid-lowering agents was started. Furthermore, the administration of octreotide and parenteral nutritional adjustments with the aim to improve portal pressure was performed. After initial worsening of ascites, the patient was returned to a general diet on day 89 after surgery. In addition, on days 94, 97, 110, 115, 126, 129, and 132 after surgery, extracts of abnobaVISCUM in increasing doses were injected intraperitoneally through the drainage for lymphatic sclerosis ("Viscum shooting"). At this stage surgical management was excluded due to a predicted morbidity risk of the patient. While ascitic fluid turned a serous color on day 94 after surgery, the amount of drained ascitic fluid also decreased during subsequent mistletoe injections until day 132. The patient was discharged from the hospital in good general condition and showed no signs of recurrence even on day 156 after surgery and at 3-month follow-up. This is the first published case on the treatment of chylous ascites and off-label injection with abnobaVISCUM extracts as a minimally invasive sclerotherapy with only minor side effects.

Advanced pancreatic cancer

Swedish multicenter, double-blind RCT on complementary mistletoe therapy - patient recruitment completed

Patient enrollment of the Swedish prospective, randomized, double-blind, multicenter, placebo-controlled clinical investigator-initiated (IIT) study in a parallel-group design on the efficacy of mistletoe extracts as an adjunct to standard therapy in advanced pancreatic cancer has been completed (MISTRAL, n=290, NCT02948309). In addition to efficacy (overall survival, primary endpoint) and safety (side effect profile, secondary endpoint), self-reported quality of life of the participants will be measured and evaluated using the two international standardized questionnaires EORTC-QLQ-C30 and EORTC-PAN-26 (secondary endpoint). Treatment of the last participant(s) in the study is scheduled to end in September 2022, according to information posted on Funding for the MISTRAL study is provided by Karolinska Hospital Stockholm. For more information on the methodology and subgroup analyses, see the following page.

New systematic review and meta-analysis confirm reduction of cancer-related fatigue with mistletoe extracts

A cancer-related fatigue syndrome (CRF) develops as a result of cancer or therapy, is characterized by tiredness or exhaustion (being not proportional to recent physical activity) and represents one of the most burdensome symptoms in cancer patients. Tiredness and exhaustion do not diminish even with sufficient sleep and can have a strong impact on life. The first-line therapy includes physical activity and psychosocial interventions. According to the S3-Guideline on Complementary Medicine in Oncological Patients, physical activity and sports, tai chi and qigong as well as yoga are recommended as non-pharmacological interventions. Sports and physical activities are not always manageable by oncological patients, e.g. by cachectic patients. Currently, methylphenidate is the only pharmacological treatment with evidence in improving CRF, however consensus on its recommendation against cancer-related fatigue seems to be unclear. Thus, further pharmacological and non-pharmacological solutions are needed. Although a large number of studies have documented positive effects of mistletoe extracts (Viscum album L) in the treatment of cancer-related fatigue, no meta-analysis has so far analysed their results in relation to clinical trials, including non-randomised intervention studies and all types of CRF questionnaires.

Recently (March 2022) a systematic review was published in the journal “Supportive Care in Cancer” on the effect of mistletoe therapy on cancer-related fatigue by Florian Pelzer, Martin Loef, David D. Martin and Stephan Baumgartner [314]. Two random-effect meta-analyses (one with 12 randomised controlled trials and one with 7 non-randomised studies of intervention) were performed. The effect sizes analysed were moderate (randomized: SMD=-0.48, p=0.006) and moderate to large (non-randomised: OR=0.36, p=0.0008). Sensitivity analyses were performed revealing robust results but high inter-study heterogeneity, possibly driven by variances in study population and methodology. Analyses reveal as well that the risk of bias was high for 11 of 12 randomised and serious for all non-randomised trials (confounding risk).

Despite a risk of bias in the included studies, the results of the systematic review and the meta-analyses indicate that mistletoe therapy can statistically significantly reduce cancer-related fatigue compared to the control group. Mistletoe therapy can be recommended as an add-on to physical activity.

Rectal cancer

Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study

In this retrospective monocentric observational study the influence of an oak mistletoe extract on the response to neoadjuvant chemoradiotherapy (NCRT) was investigated in 52 patients with locally advanced rectal cancer [318]. Fifteen patients additionally received mistletoe therapy and 37 only chemotherapy. A significantly better tumour response in terms of complete tumor remission was observed in the group with NCRT and add-on mistletoe therapy compared to the group with NCRT only (53.3 % vs. 21.6 %, p = 0.044). In addition, the downstaging was significantly higher in the group with the NCRT plus add-on mistletoe therapy (86.7% vs. 56.8%, p = 0.040). More detailed information you can find under mistletoe therapy for colorectal cancer.

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