For this type of tumour there are also various case reports available.
Last update: August 19th, 2020/AT
Grossarth-Maticek und Ziegler 2007 
This prospective, controlled cohort study in matched-pair design was part of a comprehensive long-term epidemiological study involving 10,226 cancer patients investigating various factors related to the course of the cancer disease. Therapy with mistletoe extracts was one of the investigated factors, since 1,668 patients reported using mistletoe extracts.
The influence of mistletoe therapy on psychosomatic self-regulation and survival time was analysed separately according to each tumour entity. The comparability of the two therapy groups (with and without mistletoe therapy) for the respective tumour entity was achieved by forming matched pairs.
In these two prospectively planned and conducted controlled studies, patients with malignant melanoma without recurrences, detected lymph node metastases or distant metastases were matched according to the mentioned prognostic factors and examined for overall survival, tumour progression and psychosomatic self-regulation.
All study patients received conventional therapy according to their individual condition, including – if necessary and appropriate – surgery, chemo-, radio- and immunotherapy.
In the randomised study, only melanoma patients without mistletoe therapy (and without any other immunostimulating therapy) were recruited and matched for 22 pairs; in the non-randomised study, melanoma patients treated with the mistletoe preparation Iscador in addition to conventional therapy were matched with melanoma patients treated with only conventional therapy.
In terms of overall survival, there was no significant difference between the mistletoe and control group in both studies.
The overall analysis of tumour progression showed a significant advantage for the mistletoe group in both studies with a hazard ratio (HR) of 0.49 in the randomised study and 0.72 in the non-randomised study.
In the randomised study, psychosomatic self-regulation in the mistletoe group improved significantly after 12 months compared to the control group (p = 0.0048).
In these studies, mistletoe therapy was shown to have a clinically relevant, significant effect on tumour progression (slowing of tumour progression) and an improvement in psychosomatic self-regulation in patients with malignant melanoma.
Last update: August 17th, 2020
Augustin et al. 2005 
This multicentre, controlled, epidemiological, retrospective cohort study with parallel group design, conducted according to the guidelines of "Good Epidemiological Practice" (GEP), investigated the therapeutic efficacy and safety of long-term mistletoe therapy in comparison to an untreated, only observed ("watchful waiting") control group of patients with malignant melanoma at intermediate- to high-risk (AJCC/UICC stages II and III) during post-surgical aftercare.
A total of 686 patients from various centres in Germany and Switzerland participated in the study. 329 patients were in the mistletoe group and 357 in the control group. The median follow-up/observation period was 81 months in the study group and 52 months in the control group. The median duration of therapy with the study preparation Iscador (predominantly Iscador P), which was administered two to three times a week for at least six months, was approximately 30 months.
The primary objective of efficacy was the adjusted overall survival, while secondary objectives were tumour-related survival and the adjusted risk of developing brain metastases.
The objective criterion of safety was the number of patients with documented adverse events due to mistletoe therapy.
The adjusted hazard ratio (HR, relative risk) to die of any reason during the therapy and follow-up period was significantly lower in the mistletoe group than in the control group. Comparable results were also obtained for tumour-related survival. Here the HR in the mistletoe group was even 0.41 (p = 0.002), which corresponds to a relative risk reduction of 59 percent.
The frequency of metastases, particularly brain, lung and lymph node metastases, was also significantly lower in the mistletoe group than in the control group.
In the mistletoe group, 11 patients (3.3%) developed therapy-related adverse drug reactions (ADRs) which were non-specific and only mild to moderate. In most cases the reactions subsided spontaneously within one week. In one case, treatment was terminated prematurely due to "moderate" headaches and tiredness. There were no serious side effects.
In 42 patients (12.8%) local reactions at the injection site were seen. These were mainly erythema, oedema, itching or localised pain. The local side effects were mainly mild to moderate (WHO/CTC grade 1-2) and in most cases subsided spontaneously. In 5 cases mistletoe therapy was discontinued prematurely due to local reactions.
Post-surgical supportive long-term treatment with a mistletoe extract in patients with primary malignant melanoma at intermediate- to high-risk (UICC/AJCC stages II to III) showed a significant advantage in survival compared to a control group from the same cohort without additional mistletoe therapy.
A delay in metastasis was also observed in the mistletoe group.
Last update: August 17th, 2020/AT
Kleeberg et al. 2004 
The European Organisation for Research and Treatment of Cancer (EORTC) has conducted a prospective, randomised phase III study for adjuvant treatment of melanoma patients after resection of prognostically unfavourable primary tumours (stage II, > 3mm Breslow thickness) or after curative resection of regional lymph node metastases (stage III). The aim was to evaluate the efficacy and safety of low-dose recombinant interferon-alpha 2b (rIFN-α2b) or recombinant interferon gamma (rIFN-γ) administered subcutaneously every second day for a period of twelve months or until tumour progression in comparison to an untreated control group.
To this EORTC study, the working group for internal oncology of the German Cancer Society added mistletoe therapy with Iscador M as a fourth arm, which was injected subcutaneously every other day in increasing dosages, with a seven-day break after 14 injections. As in the interferon groups, the application period was twelve months at maximum.
Thus two studies were ultimately conducted: a three-arm study without mistletoe therapy and a four-arm study with mistletoe therapy. The four-arm study was published in a short form before final publication . 830 patients were randomised in 45 institutions from 13 countries, 423 of them in the three-arm study and 407 in the four-arm study. The median follow-up was 8.2 years.
For the analysis, the two studies were partly combined and partly evaluated separately, so that the control group of the four-arm study was used for both studies.
Neither the patients treated with interferon nor those treated with Iscador showed any significant difference compared to the control in terms of disease-free or overall survival.
The results for the disease-free interval for patients in the mistletoe group were slightly below those of the control group. The results on quality of life were not published.
Five patients (4.9%) discontinued mistletoe therapy due to side effects. It is not possible to determine which side effects occurred here, as no differentiation was made between the various therapies.
During rIFN-α2b, rIFN-γ and mistletoe therapy, loss of appetite, general malaise, depressed mood, fever and local reactions at the injection site occurred. There was no organ toxicity.
In this study, no advantage of mistletoe therapy was found in terms of survival time or disease-free interval for a maximum of twelve months.
Last update: August 17th, 2020/AT