Clinical trials primarily examined the efficacy of high-dose palliative HELIXORT treatment in inoperable or metastasizing tumors:
In a retrospective study in inoperable rectal and colon cancer median survival was significantly prolonged with HELIXOR monotherapy from 4.8 to 8.6 months (colon cancer) and from 4.8 to 11 months (rectal cancer) in comparison with untreated control. One-year survival increased from 12.8% to 44.4 % (p < 0.001). Furthermore, an improved quality of life was achieved in 74 % of patients treated with HELIXOR (3).
Boie, D.; Gutsch, J.: HELIXOR bei Kolon- und Rektumkarzinom [HELIXORTM in colon and rectal cancer]. Krebsgeschehen 23, 1980, 65-76
A retrospective study in liver metastases of various primary tumours (colon, rectal, gastric and pancreatic cancer) yielded similar results as in the study mentioned above: median survival 8.1 versus 2.5 months, one-year survival 40.3 versus 6.6 % (p < 0.001) (4).
Boie, D.; Gutsch, J.; Burkhardt, R.: Die Behandlung von Lebermetastasen verschiedener Prim‰rtumoren mit HELIXOR [Treatment of liver metastases of various primary tumours with HELIXOR]. Therapiewoche 31, 1981, 1855 ñ 1869.
The efficacy of HELIXOR in combination with chemotherapy was examined in four clinical studies for palliative treatment:
In a prospective randomized trial, patients with metastasizing colorectal cancer were treated with 5-FU and folinic acid. Adjunctive HELIXORTM treatment resulted in a distinct prolongation of survival to almost double in comparison to chemotherapy alone. However this big difference in survival was not significant due to the small patient numbers in this pilot study (5)
Douwes, F. R.; Wolfrum, D. I.; Migeod, F.: Ergebnisse einer prospektiv randomisierten Studie: Chemotherapie versus Chemotherapie plus ÑBiological Response Modifierì bei metastasierendem kolorektalem Karzinom [Results of a prospective randomized study: "chemotherapy versus chemotherapy plus biological response modifier" in metastatic colorectal cancer]. Krebsgeschehen 18,6, 1986, 155 ñ 164.
A further prospective controlled study fully confirmed this positive result. Further, a significantly higher response rate was demonstrated in the HELIXORTM group in comparison to the control group. This result argues in favour of an increased efficacy of chemotherapy by combination with HELIXORTM (6).
Douwes, F. R.; Kalden, M.; Frank, G.; Holzhauer, P.: Behandlung des fortgeschrittenen kolorektalen Karzinoms [Treatment of advanced colorectal cancer]. Deutsche Zeitschrift f¸r Onkologie 20, 3, 1988, 63 ñ 67.
A distinct prolongation of median survival by additive HELIXORTM treatment was also achieved in 30 patients with chronic myeloid leukaemia: median survival in patients treated with both chemotherapy (Busulfan) and HELIXORTM was 55.7 months in comparison to 30 months in a historic control group which had a comparable prognostic structure and was only treated with Busulfan (7).
Gutsch, J.: Zum Stand der Therapie der chronisch myeloischen Leuk‰mie Erwachsener mit dem Mistelpr‰parat HELIXOR [State of HELIXORTM treatment in adult chronic myeloid leukaemia]. ƒrztezeitschrift f¸r Naturheilverfahren 23, 9, 1982, 523 ñ 544.
The efficacy of an adjunctive mistletoe treatment in malignant lymphoma and chronic leukaemia was analysed in a retrospective study with 700 patients: additional treatment with mistletoe extract resulted in a clear, but not statistically significant, prolongation of median survival (11.4 years, versus 8.6 years in patients without mistletoe therapy). In addition, patients reported an improved quality of life. Frequently voiced theoretical objections concerning a possibly unfavourable impact of mistletoe therapy on the course of malignancies of the lymphatic and haematopoetic system are refuted by this study (8).
Stumpf, C.; Rosenberger, A.; Rieger, S. ; Trˆger, W.; Schietzel, M.: Therapie mit Mistelextrakten bei malignen h‰matologischen und lymphatischen Erkrankungen ñ eine monozentrische retrospektive Analyse ¸ber 16 Jahre [Mistletoe treatment in malignant haematological and lymphatic diseases ñ a monocentre retrospective analysis of 16 years]. Forschende Komplement‰rmedizin 7, 2000, 139 ñ 146.
Increased tolerance of chemotherapy with an adjunctive mistletoe therapy:
In a prospective randomized pilot study, 44 patients with inoperable ovarian cancer, squamous cell lung carcinoma or head and neck cancer were treated with aggressive chemotherapy (ifosfamide, cisplatin) combined with radiation.
Adjunctive treatment with HELIXOR resulted in a significantly improved quality of life measured by Karnofsky performance index (p < 0.001) as well as in less nausea (p = 0.005), vomiting (p = 0.08) and cancer pain (p = 0.04). Recovery of leukopoesis was significantly quicker in the HELIXOR group (p = 0.003). Hence, the full planned dose of chemotherapy was more frequently applied in the HELIXOR group than in the control group. This may account for the higher remission rate of 78.2 % in the HELIXOR group compared to 61.9 % in the control group (9).
Gutsch, J.; K¸hne, A.: Pharmakologische und klinische Erfahrung mit dem Mistelextrakt Helixor [Pharmacological and clinical effects of the mistletoe extract HELIXOR], Heilkunst 99 (4), 1986, 156-172
The preliminary results of this pilot study could be confirmed in a prospective randomized multicentre study in 233 patients with breast, ovarian or non-small cell lung cancer according to valid standard methods and following the guidelines of good clinical practise (GCP): All patients were treated with standard polychemotherapy. Patients who were additionally treated with HELIXORTM A had a significantly better quality of life and a better tolerance of chemotherapy in comparison to the control group consistently confirmed by means of three different quality of life indices (p = 0.01/0.0007/0.003, FLIC-/TCM-/KPI-Index) and the analysis of adverse events (10).
Piao, B. K. et al. : Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian, non small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Research 24, 2004, 303-310
In a prospective randomized double-blinded pilot study, 23 patients with operated breast cancer stage I or II were treated with 6 courses of adjuvant chemotherapy (CMF). Patients additionally treated with placebo showed a significant decrease of natural killer cell activity during chemotherapy. In contrast, patients additionally treated with HELIXOR A had a significant higher natural killer cell activity (p = 0.0005) indicating that HELIXOR A is effective in the reduction of the immunosuppressive side effects of chemotherapy. It was additionally shown that a doubled-blinded design is not suitable for the evaluation of subcutaneous mistletoe therapy, because patients as well as doctors were deblinded by the evidence of the typical local inflammatory reaction at the site of subcutaneous mistletoe injection (11).
Auerbach, L.; Dostal, V.; Vaclavik-Fleck, I.; Kubista, E.; Rosenberger, A.; Rieger, S.; Trˆger, W.; Schierholz, J.M.: Signifikant hˆherer Anteil aktivierter NK-Zellen durch additive Misteltherapie bei chemotherapierten Mamma-Ca-Patientinnen in einer prospektiv-randomisierten doppelblinden Studie [Significantly higher level of activated natural killer cells in patients with breast cancer receiving a Viscum album extract during chemotherapy]. In: Scheer, Bauer, Becker, Fintelmann, Kemper, Schilcher (Hrg.): Fortschritte in der Misteltherapie. Aktueller Stand der Forschung und klinischen Anwendung [Advances in mistletoe therapy. State of the art in research and clinic], KVC-Verlag Essen 2005, 543-554].
This prospective randomized phase III trial comprised the results of 89 post-surgical patients with breast cancer, starting treatment with CAF. The patients of one group received additional mistletoe therapy (HELIXOR or another mistletoe preparation) or no additional treatment. The mistletoe group had a significantly better quality of life in 5 of 15 EORTC-QLC C30-dimensions (pain, diarrhoea, role function, insomnia,nausea/vomiting). Furthermore, a trend towards better quality of life was found in another 5 dimensions (12).
Trˆger, W.; Matijaöevi„, M.; édrale, Z.; Tisma, N.; Jezdi„, S.: Additional therapy with mistletoe extracts in breast cancer patients receiving chemotherapy ñ a prospective randomized open label pilot study. In: Scheer, Alban, Becker, Holzgrabe, Kemper, Kreis, Matthes, Schilcher (Hrg.): Die Mistel in der Tumortherapie 2. Aktueller Stand der Forschung und klinische Anwendung, KVC-Verlag Essen, 2008, 509-521
Efficacy was also proven for adjuvant HELIXOR treatment after complete cancer surgery:
In 643 patients with operated breast cancer the prognosis-improving effect of HELIXOR was examined in a prospective controlled multicentre study: Here treatment with HELIXOR or polychemotherapy (CMF/O) yielded a significant prolongation of survival (p = 0.032) in comparison to the control group without chemotherapy or HELIXOR. The clearest impact of HELIXOR treatment on survival was shown in patients with axillary lymph node metastases (13).
Gutsch, J.; Berger, H.; Scholz, G.; Denck, H.: Prospektive Studie beim radikal operierten Mammakarzinom mit Polychemotherapie, HELIXOR und unbehandelter Kontrolle [Prospective study in a radically operated breast cancer with polychemotherapy, HELIXOR and untreated control]. Deutsche Zeitschrift f¸r Onkologie 20, 4, 1988, 94 ñ 101.
In a retrospective study in 794 patients with operated breast cancer stage II-IV, adjunctive mistletoe therapy resulted in a significantly longer survival in stage III and IV (p < 0.05), but not in stage II. Comparing different adjuvant treatments the combination of mistletoe and radiation was the most effective regarding recurrence rate, disease free interval and median survival (14).
Hellan, J.; Salzer, G.; Wutzlhofer, F.: Das operierte Mammakarzinom ñ Retrospektive Auswertung [The operated breast cancer ñ a retrospective evaluation], aus: Jungi/Senn (Hrsg.) ÑKrebs und Alternativmedizin IIì. Springer Berlin Heidelberg 1990, 63 ñ 69.
Only a marginally longer survival could be demonstrated in 516 patients with breast cancer stage I (5-years survival 91 % in the mistletoe group in comparison to 83 % in the untreated control group) (15).
Hollinsky, C.; Danmayr, E.: Prognose des kleinen Mammakarzinoms (T1N0) Retrospektive Analyse anhand von 516 F‰llen [Prognosis of small breast cancer (T1N0). Retrospective analysis of 516 cases]. Deutsche Zeitschrift f¸r Onkologie 19, 3, 1987, 77 ñ 83.
In a further retrospective analysis of 1246 patients with operated breast cancer additionally treated with mistletoe preparations, the results of the former three studies could be generally confirmed: In comparison to patients of the Munich Cancer Register the 10-years survival rate was 73.3 % versus 54 %. Only in stage I an increased survival could not be demonstrated (88.1 % versus 90 %). The advantage of the mistletoe group increased with cancer staging: 10-years survival 71.6 % versus 65 % for stage II, and 55.6 % versus < 30 % for stage III (16).
Stumpf, C.; Rieger, S, Schietzel, M.: Retrospektive Untersuchung zur Therapie mit Mistelextrakten bei Mammakarzinom [Retrospective study of breast cancer patients treated with mistletoe extracts]. DZO 2005; 37 (3): 106-13.
In a retrospective study in 421 patients with operated stomach cancer adjunctive mistletoe treatment resulted in a clear prolongation of median survival: In patients without lymph node metastases median survival was prolonged by 20 months incomparison to untreated control and by 8 months in comparison to adjuvant chemotherapy. In patients with lymph node metastases, survival was prolonged by 6 months, which was comparable to the effect of adjuvant chemotherapy (17).
Salzer, G.; Frey, S.; Danmayr, E.: Die Behandlung des operierten Magenkarzinoms am Ludwig-Boltzmann-Institut f¸r Klinische Onkologie [Treatment of operated stomach cancer at the Ludwig-Boltzmann-Institute for Clinical Oncology]. Deutsche Zeitschrift f¸r Onkologie 22, 1, 1990, 21 ñ 25.
In a retrospective analysis of 695 patients with operated colorectal cancer median survival was prolonged by adjuvant mistletoe therapy by 41 months in stage I-II (N0) and by 17 months in stage III (N1-2 M0). In far advanced colorectal cancer (N3 or M1) the combination of mistletoe and chemotherapy was more effective than mistletoe or chemotherapy alone (18).
Salzer, G.; Hellan, J.; Danmayr, E.; Wutzlhofer, F.; Arbeiter, K.: Das operierte kolorektale Karzinom ñ eine retrospektive Therapieanalyse [The operated colorectal cancer ñ a retrospective analysis]. Deutsche Zeitschrift f¸r Onkologie 24, 4, 1992, 103 ñ 107.
A further retrospective study of the same centre compiled 991 patients with operated colorectal cancer. Here, recurrence rate was significantly lower in patients treated with adjuvant mistletoe therapy: compared with untreated controls, recurrence rate was reduced by 13 % in rectal cancer without lymph node metastases and by 23 % in lymph node positive colon cancer. Additionally, median survival was prolonged, most markedly in rectal cancer without lymph node metastases (213 days) and in lymph node positive colon cancer (340 days) (19).
Hellan, J.; Danmayr, E.; Hellan, M.: Stellenwert der Komplement‰rmedizin in der Behandlung onkologischer Patienten ñ dargestellt anhand des kolorektalen Karzinoms [Status of complementary medicine in the treatment of cancer patients ñ illustrated on the basis of colorectal cancer]. Deutsche Zeitschrift f¸r Onkologie 27, 4, 1995, 85 ñ 94.
In a retrospective analysis of 284 melanoma patients complete data for evaluation were available in 94 patients. Sixty-six of these patients were treated with mistletoe preparations. In spite of a significantly worse prognosis of the mistletoe group (proven metastases in 33.3% of the patients before HELIXOR treatment compared to 0% metastases in the control group) survival rates in the mistletoe group were comparable with those of control groups from the literature (5-years survival 80 %, 10-years survival 68 %) (20).
Stumpf, C.; Rosenberger, A.; Rieger, S.; Trˆger, W.; Schietzel, M.; Stein, G.M.: Retrospektive Untersuchung von Patienten mit malignem Melanom unter einer Misteltherapie [Retrospective analysis of patients with malignant melanoma during mistletoe therapy]. Forschende Komplement‰rmedizin 10, 2003, 248 ñ 255.
In retrospective studies, the efficacy of mistletoe therapy on the survival time ofpatients with 5 different malignant diseases (lymphoma/leukaemia, pancreas cancer, malignant melanoma, breast cancer and colorectal cancer) was investigated. Survival time of patients who were treated with a mistletoe preparation (HELIXOR or another mistletoe preparation) up to 10 years in an outpatient clinic (Community hospital Herdecke) were compared with the survival time of patients of a cancer registry (ìEpidemiologisches Krebsregister Saarlandî) with unknown therapy. Within the 5 tumour entities, the patients with mistletoe therapy showed a significant longer survival time than the patients from the tumour registry (21).
Stumpf, C.; Rieger, S.; Fischer, I.; Schierholz, J.; Schietzel, M.: Vergleich der ‹berlebenszeit bei Patienten mit verschiedenen Tumorentit‰ten ñ Retrospektive Untersuchung zur Wirksamkeit von Misteltherapie vs. Daten eines Tumorregisters. [Comparison of survival time of patients with different tumor entities ñ results of retrospective investigations for efficacy of mistletoe therapy vs. data from a tumor registry]. In: Scheer, Alban, Becker, Holzgrabe, Kemper, Kreis, Matthes, Schilcher (Hrg.): Die Mistel in der Tumortherapie 2. Aktueller Stand der Forschung und klinische Anwendung, KVC-Verlag Essen, 2008, 427-440
In a controlled pharmacoepidemiological cohort study in 741 breast cancer patients after termination of adjuvant radio-/chemotherapy, HELIXOR treatment resulted in a significantly lower frequency of therapy- or disease-related complaints as compared to the control group frequency (p<0,001). A clear increase of this HELIXOR-related benefit was seen from year to year during the 5-year treatment period. Especially the the frequency of complaints from pain, fatigue and mucositis decreased. (22).
Beuth, J.; Schneider, B.; Schierholz, J.M.: Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study. Anticancer Research 2008;28(1B):523-7.
In two further studies, the efficacy of high-dose intrapleural HELIXOR instillation in malignant pleural effusion was evaluated:
In a prospective study with 20 consecutive hospitalized patients with pleural effusion in far advanced cancer, complete remission according to WHO criteria could be achieved in 72 %, together with an excellent tolerance of HELIXORTM instillation (side effect rate 1.2 % WHO grade 1). The decrease in pleural effusion volume and cancer cells within the effusion was significantly dependent on the frequency and dose of HELIXOR instillations (p < 0.001) (23).
Stumpf, C.; Schietzel, M.: Intrapleurale Instillation eines Extraktes aus Viscum album (L.) zur Behandlung maligner Pleuraerg¸sse [Intrapleural instillation of a Viscum album L. extract (mistletoe) for therapy of malignant pleural effusion]. Tumordiagnostik und Therapie 15, 1994, 57-62.
In a prospective randomized study including 30 patients with malignant pleural effusion high-dose HELIXOR instillation resulted in a significantly higher response rate in comparison to standard therapy with doxycycline (91 % versus 66.6 %, p < 0.05). In addition, the side effect index was significantly lower (p < 0.05) (24).
Kim, M.H.; Lee, S.H.; Kim, S.C.; Kim, Y.K.; Park, S.H.: Comparative study on the effects of a Viscum album (L.) extract (mistletoe) and doxycycline for pleurodesis inpatients with malignant pleural effusion. Korean Journal of Medicine 57, Suppl. 2, 1999.
Currently HELIXORTM will be administered intralesionally in a growing number.
In a pilot study, the efficacy of intratumoural injection of HELIXOR M was investigated in 6 patients with hepatocellular carcinoma and in 21 patients with liver metastases of colorectal cancer. Using ultrasound control, 100 ñ 2,500 mg HELIXORÆ M was injected into the liver tumours one to three times weekly. In hepatocellular carcinoma, tumour remission could be achieved in 83 % of patients, combined with a significant decrease of the tumour marker AFP. In the patients with liver metastases, a decline in the tumour marker and a remission of the metastases was achieved in 52 % of cases (25).
Matthes, H.: Intral‰sionale Mistelinjektionen in Lebermetastasen bei kolorektalem Karzinom und in das prim‰re Hepatozellul‰re Karzinom (HCC), (Abstract). [Intralesional mistletoe injections into hepatic metastases in colorectal carcinoma and into primary hepatocellular carcinoma]. Der Merkurstab 1997;50 Sonderheft Juni), 41
In a further pilot study the effect of HELIXOR M on inoperable pancreatic cancer was evaluated in 12 patients. HELIXOR M was applicated intralesionally by endoscopic ultrasound-guided fine-needle injection. According to the WHO response criteria, 8 % of the patients showed complete response, 50 % partial response and 33 % no change. This remission rate is superior to chemotherapy in inoperable pancreatic cancer (about 10 %). No major toxicity was observed. Quality of life improved in more than 83 % (26).
Matthes, H.;Buchwald, D.; Krˆz, M.; Schad, F.: Integrative Therapiemˆglichkeiten des inoperablen Pankreaskarzinoms ñ eine ‹bersicht. [Integrative therapy options for inoperable pancreatic carcinoma ñ an overview]. DZO 2008, 40 (3): 106-10