
48 prospective comparative trials investigated the influence of mistletoe therapy on tumour diseases, 30 of which are randomised controlled trials (RCT Review Table) and 18 are non-randomised studies (N-RCT Review Table). Most of the non-randomised studies employed specific methods to control for confounding: Patients were alternately allocated to the test or control groups in two studies; prospective matched patient pairs were recruited from a large pool of patients in nine studies; patients were matched for evaluation in one study; there was a prognostic disadvantage for the mistletoe group in one study; and in another study an independent senior hospital physician allocated patients to the mistletoe group and control groups respectively.
30 RCTs enrolled 3396 patients, 18 N-RCTs enrolled more than 4068 patients (the size of one control group was not specified). The studies have been carried out in university hospitals, other academic hospitals, large communal hospitals and specialist oncology clinics.

These prospective comparative trials investigated mistletoe therapy in the treatment of: breast carcinoma (n = 14), lung carcinoma (n = 8), colon and rectum carcinoma (n = 6), stomach carcinoma (n = 4), gastrointestinal cancer (n = 1), bladder carcinoma (n01), melanoma (n = 4), ovarian carcinoma (n = 6), genital carcinoma (n = 1), uterus carcinoma (n=4), cervical carcinoma (n = 4), cervical dysplasia (n=2), head and neck tumours (n = 1), osteosarcoma (n=1), malignant pleural effusion (n = 1). The stage of tumour disease varied in each study, ranging from early diagnosis tumours to advanced tumour disease.

The following endpoints were identified for the trials: Survival time (n = 34); tumour remission or tumour recurrence (n = 15); quality of life and coping behaviour (n = 16), reduction in side effects of conventional therapies such as chemotherapy, radiotherapy or surgery (n = 10).

Iscador® was administered in 37 studies, Helixor in eight studies, Isorel® and Abnobaviscum® in two studies each. Dosage mostly followed recommendations of the manufacturer - i.e. low dosage at the beginning of therapy; thereafter gradually increasing to the maximum well-tolerated dosage. In one study, mistletoe extracts were also administered according to lectin content (1ng/kg bodyweight) [3]. The mistletoe extracts were administered by subcutaneous injection, with the exception of five studies where administration was by infusion [4, 5, 34], intrapleural [22], or intravesical [17a]. The control group either received no further treatment (n = 27), treatment with an additional placebo (n = 3), Lentinan (n = 1), BCG (n = 2), Doxycyxlin (n = 1), Etoposide (n=1), or partly hormone treatment (n = 1).
In 13 trials mistletoe therapy was administered concurrently with conventional treatments (chemotherapy, radiotherapy, surgery) [1, 4, 4a, 5, 7, 8, 8a, 9, 24, 26, 34, 35, 37]. Four of these studies at least partially involved patients with advanced metastatic disease [5, 7, 8, 26]. Ten studies assessed reduction of side effects of the conventional cytoreductive therapies (including surgery) [1, 4, 4a, 5, 9, 24, 26, 34, 36, 37]. In 32 trials mistletoe treatment was administered, at least partially, in an adjuvant setting following primary surgery or radiotherapy [1, 4, 5, 8a, 10, 11, 13-17, 17a, 23, 25, 26, 28-33, 35-37].


The methodological quality of the studies varied considerably. The quality of several trials—design, execution and documentation—is in some respects far below the standards deemed necessary or optimal today, especially in some of the older studies. However, during recent years the quality has improved and a number of recent studies have been well executed. For a detailed evaluation of study quality see [18-21]; some of the most important studies have been comprehensively described: Piao 2004, Grossarth 2001, 2006, 2007 and 2008, Kleeberg 2004.

The prospective comparative randomised trials predominantly show benefits of mistletoe therapy with respect to survival time, quality of life and reduction in the side effects of conventional therapies. While the quality of the studies varies widely, the overall conclusions do not essentially change if only the good quality studies are taken into consideration. A reduction in side effects of conventional therapies and improvement of quality of life appears to be best substantiated. In this regard, the study is easier to conduct and less complicated, mainly due to a shorter study duration—that is, if the issue of blinding is excluded (which can only be carried out pro forma because of the high rates of unblinding [1, 27] with subcutaneous administration). Survival benefit has been shown, but not beyond critique. Survival time is possibly dependent on the duration of therapy [2, 11] and on additional factors such as good coping behaviour (self-regulation) [11, 12]. It is not possible to make reliable statements regarding tumour remission and disease-free intervals due to methodological weaknesses in the prospective comparative trials. 18 of the studies were embedded in the same large epidemiological cohort study (details, see Grossarth et al. ).

RCT-Table in English as PDF-download

N-RCT-Table in English as PDF-download
Gunver S. Kienle, MD
Last modified:
May 2010
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