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 clinicaltrials.gov. Funding for the MISTRAL study is provided by Karolinska Hospital Stockholm. For more information on the methodology and subgroup analyses, see the following page.
Last Update: September 27th, 2022/AT
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 . 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. Since the pooled effect estimate presented in the systematic review was similar to other cancer-related fatigue interventions, mistletoe therapy is recommended as an alternative treatment or add-on to physical activity in prospective multimodal therapy concepts, especially when a pharmacological treatment is needed.
Last Update: April 8th, 2022/AT1