Questions About Cancer? 1-800-4-CANCER

Mistletoe Extracts (PDQ®)

Health Professional Version
Last Modified: 05/10/2013

Human/Clinical Studies

Iscador
Eurixor
Isorel
Helixor
Abnoba-viscum
Current Clinical Trials

Mistletoe has been evaluated as a treatment for people with cancer in numerous clinical studies.[1-14] Reviewed in [15-20] One phase II study in Israel involved carboplatin /gemcitabine in combination with mistletoe as a complementary treatment in patients with non-small cell lung cancer (NCT00516022). Most studies have been conducted in Europe, primarily in Germany and Austria. However, in 2002, the National Center for Complementary and Alternative Medicine in cooperation with the National Cancer Institute (NCI) began accruing patients to a phase I trial (NCCAM-02-AT-260) of mistletoe (Helixor A) and gemcitabine in patients with advanced solid tumors. The Helixor A and gemcitabine combination showed limited toxicity with clinical benefit in 48% of patients.[21] The trial is now closed and the data is being analyzed. Another U.S. trial (NCT00283478) of the mistletoe extract Iscar with gemcitabine versus gemcitabine alone as a second-line therapy for non-small cell lung cancer patients who have failed one prior line of chemotherapy has been completed.

The mistletoe extracts and products studied in clinical trials were Iscador, Eurixor, Helixor, Lektinol, Isorel, Abnoba-viscum,[22] and recombinant lectin ML-1 (refer to the tables at the end of this section for more information).

Approximately half of the reported studies were controlled studies, and a majority of these were randomized clinical trials. Survival was the principal endpoint measured in most reported studies; however, other endpoints included tumor response, tumor recurrence, and quality of life. A systematic review of all controlled clinical studies of mistletoe found consistent improvement in chemotherapy-associated fatigue as well as other quality-of-life measures.[23]

Although mistletoe was found to be therapeutically effective in most of the reported studies, many of the studies had one or more major weaknesses that raised doubts about the reliability of the findings. These weaknesses include registration of small numbers of patients; presence of large numbers of patients who either were not evaluable or were otherwise excluded from the analyses; failure to adequately document mistletoe use, mistletoe dose, and/or interruptions of mistletoe use; absence of control subjects or use of historical control subjects; use of inadequate randomization procedures; absence of treatment blinding; extensive use of subset analysis; and the measurement of mean as opposed to median survival. (Note: In studies with small numbers of patients, the mean survival time [i.e., the average survival time] can be greatly exaggerated if one or more patients exhibit unusually long survival; median survival, therefore, is a less biased measure.) In addition, evaluation of the studies is often hindered by incomplete descriptions of the study design and by incomplete reporting of clinical data, including data about previous and concurrent therapies received by the patients. A selection of studies is discussed below, organized by the type of mistletoe extract used.

Iscador

A three-arm, randomized phase III trial that involved 408 patients with previously untreated, inoperable non-small cell lung cancer was conducted between 1978 and 1987.[24] Patients were randomly assigned to one of the following treatments: (1) subcutaneous injection 3 times a week with IscadorU or IscadorQ (refer to the General Information section of this summary for more information); the concentration of mistletoe was increased during a seven-injection sequence or cycle, followed by a 3-day pause, and then the process was repeated; IscadorU was administered for two cycles, followed by two cycles of IscadorQ; both mistletoe preparations contained mercury); (2) intramuscular injection once a week with Polyerga Neu, which is a sheep spleen glycopeptide that is reported to be an immunostimulant and an inhibitor of tumor cell glycolysis; and (3) intramuscular injection once a week with a vitamin B mixture, which served as a placebo. Complete follow-up information was available for 337 patients, and 312 patients (105 Iscador treated, 100 Polyerga Neu treated, and 107 placebo treated) were included in the survival analysis. No statistically significant differences in survival were found between the three groups. Median survival for the Iscador group was 9.1 months; for the Polyerga Neu group, it was 9.0 months; and for the placebo group, it was 7.6 months. The researchers reported that 11.5% of the patients in the Iscador group survived 2 years from the time they entered the trial; the corresponding survival values for the Polyerga Neu and the placebo groups were 13.9% and 10.1%, respectively. In addition, no differences were found between the three groups with respect to tumor response, median body weight, blood chemistry values, Karnofsky Performance Status, and quality of life. However, more patients in the Iscador group than in the Polyerga Neu or the placebo groups reported subjective improvement in feelings of well-being (59.4% vs. 43.2% and 44.8%, respectively).

Another randomized phase III trial of mistletoe as a treatment for people with cancer involved 830 patients with high-risk melanoma (i.e., a primary tumor >3 mm in diameter and no regional lymph nodes positive for cancer or a primary tumor of any size, one or two regional lymph nodes positive for cancer, and no distant metastases) who were randomly assigned to one of the following four groups after potentially curative surgery: (1) treatment with low-dose interferon -alpha, (2) treatment with low-dose interferon-gamma, (3) treatment with IscadorM, or (4) no further treatment. Both types of interferon and IscadorM were administered by subcutaneous injection for a period of 1 year.[5] The interferon injections were administered every other day, whereas IscadorM was administered 3 times a week. After 8 years of follow-up, no increase in survival time or increase in time until melanoma recurrence was demonstrated for mistletoe treatment or treatment with either type of interferon. A nonrandomized, case-control study of long-term mistletoe extract for patients with melanoma, however, showed a survival advantage among patients with high-risk disease.[25]

Three other studies of mistletoe were described in a single published report.[4] One of the three studies was a large cohort study on the effectiveness of Iscador as a treatment for people with rectal cancer, colon cancer, breast cancer, stomach cancer, or lung cancer.[4] The second and third studies were small, prospective, randomized, matched-pair studies (one randomized, one nonrandomized) that involved patients who were selected from a group of 8,475 individuals who had not been treated with mistletoe.[4]

These studies are summarized in Table 1. The overall conclusion of the authors in the report of these three studies was that Iscador treatment can produce a clinically significant increase in survival in cancer patients. However, there were several weaknesses in the design and execution of these studies. In a large cohort study, the investigators were unable to find matching cohorts for 61% of eligible patients, and even among the patients for whom matches were found, fewer than two-thirds were judged to adhere strictly to the matching criteria; thus, the final analysis contained fewer than 25% of eligible patients. In the two small prospective studies, no records on the amount or duration of Iscador use were kept.

The use of Iscador as an adjuvant treatment has been examined in several studies. In the following studies, Iscador proved safe and effective and also showed a significant survival advantage over untreated controls.

In a phase l/ll trial of Iscador as an adjuvant postoperative treatment for superficial bladder cancer, mistletoe extract was found to be a safer and more effective alternative to Bacillus Calmette-Guérin (BCG). Thirty patients were administered Iscador instillations 4 weeks after surgery. Patients treated with Iscador did equally well with fewer side effects than a group of historical controls treated with BCG.[26,27]

A retrospective multicenter cohort study of parallel groups examined Iscador as a postoperative adjuvant using safety and efficacy as the main endpoints. A total of 1,442 patient records (710 treated patients and 732 untreated controls) were randomly selected from medical institutions that provided both standard and alternative treatments. Safety and efficacy were measured by the number and severity of adverse drug reactions. The treatment group showed significantly less adverse reactions (confidence interval = 95%; P = < .001) compared with the controls.[28,29]

A multicenter, controlled, retrospective observational cohort study that involved nonmetastatic colorectal cancer patients treated between 1993 and 2002 was conducted to evaluate safety and efficacy measures with Iscador. Eight hundred and four consecutive colorectal patients (429 treated with Iscador and 375 controls) from 26 hospitals and practices were included. Iscador was well tolerated, with a significant reduction in adverse events, a higher rate of symptom relief, and improved disease-free survival compared with the control group. The study concluded the use of Iscador has a beneficial effect as an adjuvant therapy and long-term treatment for patients with stage I to III colorectal cancer.[30]

In another retrospective multicenter cohort study to determine safety and efficacy of Iscador as an adjuvant long-term treatment following surgery for malignant melanoma, 686 patient records were examined (e.g., 357 untreated controls and 329 treated with Iscador). Safety, efficacy, and a cluster of survival endpoints (tumor-related, disease-free, brain-metastases free, and overall survival) were measured. Only mild to intermediate adverse drug reactions were seen in the treated group. Survival analyses showed no evidence of tumor enhancement and no increased incidence of brain or other metastases in the Iscador group. Results suggest significant survival benefit for all survival-related endpoints in the treatment group.[25]

Eurixor

Five randomized controlled trials of Eurixor have been published as peer-reviewed articles. The largest of these studies involved 477 patients with squamous cell carcinoma of the head and neck.[2] Reviewed in [15] These patients were randomly assigned to treatment with surgery or surgery and radiation therapy, and they were randomly assigned again to either no additional treatment or treatment with Eurixor. This double randomization produced the following four groups: (1) 105 patients treated with surgery alone; (2) 97 patients treated with surgery and Eurixor; (3) 137 patients treated with surgery and radiation therapy; and (4) 138 patients treated with surgery, radiation therapy, and Eurixor. Eurixor was administered in four treatment cycles over a 60-week period. Each treatment cycle lasted 12 weeks and was followed by a 4-week break period. During each cycle, Eurixor was administered by subcutaneous injection twice a week. Each injection contained enough standardized mistletoe extract to yield a dose of 1 nanogram of ML-1 lectin per kilogram of body weight. The results of this randomized trial showed that treatment with Eurixor did not improve either 5-year disease-free survival or 5-year disease-specific survival. In addition, no stimulation of the immune system or improvement in quality of life was found with Eurixor treatment.

It has been suggested that a less-than-optimum dose of mistletoe was administered to patients in this trial.[4] The same dose of Eurixor, however, has been used in other clinical studies, including studies in which benefit was reported.[1,31] In addition, both the dose and the duration of Eurixor treatment in this trial are consistent with those recommended by the manufacturer.[2]

A prospective, randomized phase II trial involved 45 patients who had noninvasive bladder cancer.[3] After surgery, the patients were randomly assigned to receive either three cycles of treatment with Eurixor or no further therapy. The goal of the study was to determine whether Eurixor treatment could reduce bladder cancer recurrence. Twenty-three patients were randomly assigned to the treatment group, and 22 were randomly assigned to the control group. Each cycle of Eurixor treatment consisted of 3 months of subcutaneous injections, administered twice a week, followed by a 3-month break period. One milliliter of Eurixor was administered at each injection. After 18 months of follow-up, 11 recurrences were observed in the treatment group, and 8 were observed in the control group. The average time of recurrence for the treatment group was 6.3 months; for the control group, it was 6.4 months. The median disease-free interval for the treatment group was 9 months; for the control group, it was 10.5 months. None of these differences was considered significant.

A major concern about this study, however, is that the dose of lectin ML-1 administered to patients was not adjusted for body weight. If different batches of Eurixor were used for individual patients, the patients may not have received uniform doses throughout the trial. Each milliliter of Eurixor has been reported to contain 50 to 70 nanograms of ML-1. Reviewed in [1,31,32] Therefore, the dose of lectin administered to a person weighing 120 pounds (approximately 55 kg) could have ranged from 0.91 nanograms per kilogram body weight to 1.27 nanograms per kilogram body weight. For a person weighing 160 pounds (approximately 73 kg), the dose of lectin could have ranged from 0.68 nanograms per kilogram body weight to 0.96 nanograms per kilogram body weight. As indicated above, the manufacturer of Eurixor recommends a dose of 1 nanogram per kilogram body weight. Since 33 of the 45 patients in this trial were men, and men tend to weigh more than women, it is conceivable that a substantial fraction of the patients were treated with lower-than-recommended doses of ML-1.

Isorel

Only two trials of Isorel have been reported in the publicly available, online indexed peer-reviewed medical literature. In one study, 64 patients with advanced colorectal cancer (Dukes C and D) were randomly assigned to three groups: (1) surgery and chemotherapy; (2) surgery and chemotherapy plus Isorel; and (3) surgery alone. Patients receiving treatment with Isorel had a significantly better median survival advantage and a better cumulative survival advantage than patients in the other two groups. In addition there were no side effects to treatment in the Isorel group.[33]

Another study showed that perioperative use of Isorel in patients with cancer of the digestive tract resulted in an increase in lymphocytes through 14 days of drug administration. In a group of 70 surgically treated patients, 40 patients were assigned to the Isorel-treated group, and 30 patients were assigned to the control group. The treatment group showed an increase in CD4/CD8 ratio (P = < .05) from the start to the end of treatment and an increase in natural killer (NK) cell determinants. NK cell activity and lymphocyte levels declined in the controls. Quality-of-life measures also increased in the treatment group.[34]

Helixor

In a three-arm randomized trial, breast cancer patients were randomly assigned to one of the following groups after surgery: Helixor, chemotherapy, or control. Some patients in each group were also treated with local radiation therapy. The number of evaluable patients in the chemotherapy group was 177, with survival in the chemotherapy group superior to that in the control group and equivalent to that in the Helixor group.[35] In another three-arm randomized trial, metastatic colorectal cancer patients were randomly assigned to receive chemotherapy only (n = 20), chemotherapy plus Helixor (n = 20), or chemotherapy plus Ney-Tumorin (n = 20); Ney-Tumorin is a mixture of peptides and proteins from 15 different organs of fetal and young pigs or cows that is reported to have both antitumor and immunostimulatory properties. The mean survival time (in months) of patients treated with either Helixor or Ney-Tumorin was approximately twice that of patients treated with chemotherapy only.[36] The use of Helixor has also been examined in other studies.[37-40]

Abnoba-viscum

No tumor response was seen in any of the 25 patients in a phase ll trial that examined the effect of a mistletoe extract in metastatic colorectal cancer resistant to standard treatment (5-fluorouracil and leucovorin chemotherapy), which used an extract known as Abnoba-viscum. The endpoint of the study was objective tumor response. Patients were administered a gradually increasing daily dose of 0.15 mg to 15 mg. Treatment duration ranged from 4 weeks to 66 weeks. Toxicity levels were mild. Some patients reported relief of disease symptoms.[41]

Table 1. Use of Iscador in Cancer Treatment: Clinical Reports Describing Therapeutic Endpointsa
Reference Citation(s) Type of Study Type(s) of Cancer No. of Patients: Enrolled; Treated; Controlb Strongest Benefit Reportedc Concurrent Therapyd Level of Evidence Scoree 
[24]Randomized trialLung, non-small cell, inoperable408; 105; 107fSubjective improvement in quality of lifeYesg1iiA
[42]Randomized trialLung, non-small cell, stages I–IV218; 87; 96Improved median survival, LN+ patients onlyNo1iiA
[5]Randomized trialMelanoma, stages II–III204; 102; 102NoneNo1iiA
[28]Comparative, retrolective, cohort studyBreast, stages I–IV1,442; 710; 732Improved survivalYes2B
[25]Comparative, retrolective, cohort studyMelanoma, stages II–III686; 329; 357Improved survivalUnknown2A
[4]Cohort studyBreast, stage III8,475h; 17i; 17iImproved mean survivalYesNone
[4]Cohort studyVarious types, stages I–IV8,475h; 39i; 39iImproved mean survivalYesNone
[4]Cohort studyVarious types, stages I–IV10,226h; 396i; 396iImproved mean survivalYes3iiiA
[30]Retrospective, observational cohort studyNonmetastatic colorectal804; 429; 375Lower incidence of diarrhea, nausea, loss of appetite, dermatitis, fatigue, and mucositisYes2C
[43]Nonconsecutive case seriesPancreas 292; 292; various historical controlsImproved median survivalYes3iiiA
[44]Case report Lung, small cell, stage IV1; 1; NonePartial responseYesNone

LN+ = lymph node-positive disease; No. = number.
aSee text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
bNumber of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
cStrongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
dChemotherapy, radiation therapy, hormonal therapy, or cytokine therapy administered/allowed at the same time as mistletoe therapy.
eFor information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
fControl patients were treated with a vitamin B mixture as a placebo; 100 additional evaluable patients were treated with Polyerga Neu, a sheep spleen glycopeptide reported to be an immunostimulant and an inhibitor of tumor cell glycolysis; treatment with Polyerga Neu was not found to be beneficial.
gRadiation therapy for metastases distant from the site of the primary tumor was permitted; radiation therapy to the primary tumor site or use of other anticancer treatment was not permitted.
hAmong 10,226 cancer patients enrolled in a retrospective matched-pair, case-control study, 1,751 had been treated with Iscador or another mistletoe product and 8,475 had not been treated with mistletoe; from the 8,475 untreated patients, two sets of matched pairs were formed for prospective studies; in the prospective studies, one member of each pair was randomly assigned to be treated with Iscador and the other member served as a control subject.
iPatients were strictly matched according to gender, year of birth ±3 years, year of diagnosis ±3 years, type of tumor, stage of disease, and conventional therapy received.

Table 2. Use of Eurixor in Cancer Treatment: Clinical Reports Describing Therapeutic Endpointsa
Reference Citation(s) Type of Study Type(s) of Cancer No. of Patients: Enrolled; Treated; Controlb Strongest Benefit Reportedc Concurrent Therapyd Level of Evidence Scoree 
[3]Randomized trialBladder, noninvasive45; 23; 22NoneNo1iiDi
[1,31]Randomized trialBrain, glioma; 74% of patients, stages III–IV; 26% of patients, no stage information47; 20; 18Improved survival, stages III–IV patients onlyYes1iiA
[45,46]Randomized trialColorectal, metastatic107; 38; 41Improved quality of lifeYes1iiA
[2]Randomized trialHead and neck, squamous cell, stages I–IV495; 235f; 242fNoneYesf1iiA

No. = number.
aSee text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
bNumber of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
cStrongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
dChemotherapy, radiation therapy, hormonal therapy, or cytokine therapy administered/allowed at the same time as mistletoe therapy.
eFor information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
fThis trial was a four-arm trial; patients were randomly assigned to surgery only or to surgery plus radiation therapy, followed by a second randomization to no mistletoe treatment or to treatment with Eurixor; the resulting treatment groups contained the following numbers of evaluable patients: surgery only = 105, surgery plus Eurixor = 97, surgery plus radiation therapy = 137, and surgery plus radiation therapy plus Eurixor = 138; radiation therapy and Eurixor treatment overlapped; no treatment approach was superior in terms of disease-free survival, disease-specific survival, improvement in quality of life, or stimulation of the immune system; in the table, mistletoe-treated and nontreated (control) patients were grouped (i.e., number treated = 97 + 138 = 235, and number control = 105 + 137 = 242).

Table 3. Use of Helixor in Cancer Treatment: Clinical Reports Describing Therapeutic Endpointsa
Reference Citation(s)  Type of Study Type(s) of Cancer No. of Patients: Enrolled; Treated; Controlb Strongest Benefit Reportedc Concurrent Therapyd Level of Evidence Scoree 
[35]Randomized trialBreast, stages I–III692; 192; 274Improved survivalYes1iiA
[36]Randomized trialColorectal, metastatic60; 20; 20Improved mean survivalYes1iiA

No. = number.
aSee text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
bNumber of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
cStrongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
dChemotherapy, radiation therapy, hormonal therapy, or cytokine therapy administered/allowed at the same time as mistletoe therapy.
eFor information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.

Table 4. Use of Other Mistletoe Products in Cancer Treatment: Clinical Reports Describing Therapeutic Endpointsa
Reference Citation(s) Type of Study Product Tested Type(s) of Cancer No. of Patients: Enrolled; Treated; Controlb Strongest Benefit Reportedc Concurrent Therapyd Level of Evidence Scoree 
[13]Randomized controlled trialPS76A (Lektin)Breast352; 176; 176Improved quality of lifeYes1iC
[33]Randomized trialIsorelColorectal64; 50; 14Improved survival and tolerance to either adjuvant or palliative treatmentYes1iiA
[34]Nonrandomized controlled trialIsorelDigestive tract70; 40; 30Enhanced cellular immunity and improved quality of lifeNo2C
[41]Nonrandomized controlled trialAbnoba-viscum QuercusMetastatic colorectal25; 25; noneNoneYes2Diii
[22]Nonrandomized controlled trialViscum fraxini-2Hepatocellular carcinoma23; 23; noneImproved survivalNo2Dii

No. = number.
aSee text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
bNumber of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
cStrongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
dChemotherapy, radiation therapy, hormonal therapy, or cytokine therapy administered/allowed at the same time as mistletoe therapy.
eFor information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.

Current Clinical Trials

Check NCI’s list of cancer clinical trials for cancer CAM clinical trials on mistletoe extract that are actively enrolling patients.

General information about clinical trials is also available from the NCI Web site.

References
  1. Lenartz D, Dott U, Menzel J, et al.: Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 20 (3B): 2073-6, 2000 May-Jun.  [PUBMED Abstract]

  2. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al.: The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 37 (1): 23-31, 2001.  [PUBMED Abstract]

  3. Goebell PJ, Otto T, Suhr J, et al.: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168 (1): 72-5, 2002.  [PUBMED Abstract]

  4. Grossarth-Maticek R, Kiene H, Baumgartner SM, et al.: Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 7 (3): 57-66, 68-72, 74-6 passim, 2001 May-Jun.  [PUBMED Abstract]

  5. Kleeberg UR, Suciu S, Bröcker EB, et al.: Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer 40 (3): 390-402, 2004.  [PUBMED Abstract]

  6. Viscum album. In: Homoeopathic Pharmacopoeia Convention of the United States.: Homoeopathic Pharmacopoeia of the United States. Washington, DC: 2002, Monograph 9444 Visc. 

  7. Tröger W, Jezdić S, Ždrale Z, et al.: Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone . Breast Cancer: Basic and Clinical Research 3: 35-45, 2009. 

  8. Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed 13 (5): 285-92, 2006.  [PUBMED Abstract]

  9. Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed 14 (3): 140-7, 2007.  [PUBMED Abstract]

  10. Grossarth-Maticek R, Ziegler R: Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res 13 (3): 107-20, 2008.  [PUBMED Abstract]

  11. Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador. Arzneimittelforschung 57 (10): 665-78, 2007.  [PUBMED Abstract]

  12. Bar-Sela G, Goldberg H, Beck D, et al.: Reducing malignant ascites accumulation by repeated intraperitoneal administrations of a Viscum album extract. Anticancer Res 26 (1B): 709-13, 2006 Jan-Feb.  [PUBMED Abstract]

  13. Wetzel D, Schäfer M: Results of a randomised placebo-controlled multicentre study with PS76A2 (standardised mistletoe preparation) in patients with breast cancer receiving adjuvant chemotherapy. [Abstract] Phytomedicine 7 (Suppl 2): A-SL-66, 2000. 

  14. Schöffski P, Riggert S, Fumoleau P, et al.: Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Ann Oncol 15 (12): 1816-24, 2004.  [PUBMED Abstract]

  15. Stauder H, Kreuser ED: Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie 25 (4): 374-80, 2002.  [PUBMED Abstract]

  16. Kienle GS, Berrino F, Büssing A, et al.: Mistletoe in cancer - a systematic review on controlled clinical trials. Eur J Med Res 8 (3): 109-19, 2003.  [PUBMED Abstract]

  17. Kienle GS, Glockmann A, Schink M, et al.: Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res 28: 79, 2009.  [PUBMED Abstract]

  18. Horneber MA, Bueschel G, Huber R, et al.: Mistletoe therapy in oncology. Cochrane Database Syst Rev (2): CD003297, 2008.  [PUBMED Abstract]

  19. Kienle GS, Kiene H: Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res 12 (3): 103-19, 2007.  [PUBMED Abstract]

  20. Ernst E, Schmidt K, Steuer-Vogt MK: Mistletoe for cancer? A systematic review of randomised clinical trials. Int J Cancer 107 (2): 262-7, 2003.  [PUBMED Abstract]

  21. Mansky PJ, Wallerstedt DB, Sannes T, et al.: NCCAM/NCI phase I study of mistletoe extract and gemcitabine in patients with advanced solid tumors. [Abstract] J Clin Oncol 28 (Suppl 15): A-2559, 2010. 

  22. Mabed M, El-Helw L, Shamaa S: Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. Br J Cancer 90 (1): 65-9, 2004.  [PUBMED Abstract]

  23. Kienle GS, Kiene H: Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther 9 (2): 142-57, 2010.  [PUBMED Abstract]

  24. Dold U, Edler L, Mäurer HCh, et al., eds.: [Adjuvant Cancer Therapy in Advanced Non-Small Cell Bronchial Cancer: Multicentric Controlled Studies To Test the Efficacy of Iscador and Polyerga]. Stuttgart, Germany: Georg Thieme Verlag, 1991. 

  25. Augustin M, Bock PR, Hanisch J, et al.: Safety and efficacy of the long-term adjuvant treatment of primary intermediate- to high-risk malignant melanoma (UICC/AJCC stage II and III) with a standardized fermented European mistletoe (Viscum album L.) extract. Results from a multicenter, comparative, epidemiological cohort study in Germany and Switzerland. Arzneimittelforschung 55 (1): 38-49, 2005.  [PUBMED Abstract]

  26. Elsässer-Beile U, Leiber C, Wetterauer U, et al.: Adjuvant intravesical treatment with a standardized mistletoe extract to prevent recurrence of superficial urinary bladder cancer. Anticancer Res 25 (6C): 4733-6, 2005 Nov-Dec.  [PUBMED Abstract]

  27. Elsässer-Beile U, Leiber C, Wolf P, et al.: Adjuvant intravesical treatment of superficial bladder cancer with a standardized mistletoe extract. J Urol 174 (1): 76-9, 2005.  [PUBMED Abstract]

  28. Bock PR, Friedel WE, Hanisch J, et al.: Retrolective, comparative, epidemiological cohort study with parallel groups design for evaluation of efficacy and safety of drugs with "well-established use". Forsch Komplementarmed Klass Naturheilkd 11 (Suppl 1): 23-9, 2004.  [PUBMED Abstract]

  29. Bock PR, Friedel WE, Hanisch J, et al.: [Efficacy and safety of long-term complementary treatment with standardized European mistletoe extract (Viscum album L.) in addition to the conventional adjuvant oncologic therapy in patients with primary non-metastasized mammary carcinoma. Results of a multi-center, comparative, epidemiological cohort study in Germany and Switzerland] Arzneimittelforschung 54 (8): 456-66, 2004.  [PUBMED Abstract]

  30. Friedel WE, Matthes H, Bock PR, et al.: Systematic evaluation of the clinical effects of supportive mistletoe treatment within chemo- and/or radiotherapy protocols and long-term mistletoe application in nonmetastatic colorectal carcinoma: multicenter, controlled, observational cohort study. J Soc Integr Oncol 7 (4): 137-45, 2009.  [PUBMED Abstract]

  31. Lenartz D, Stoffel B, Menzel J, et al.: Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 16 (6B): 3799-802, 1996 Nov-Dec.  [PUBMED Abstract]

  32. Kleijnen J, Knipschild P: Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine 1: 255-60, 1994. 

  33. Cazacu M, Oniu T, Lungoci C, et al.: The influence of isorel on the advanced colorectal cancer. Cancer Biother Radiopharm 18 (1): 27-34, 2003.  [PUBMED Abstract]

  34. Enesel MB, Acalovschi I, Grosu V, et al.: Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients. Anticancer Res 25 (6C): 4583-90, 2005 Nov-Dec.  [PUBMED Abstract]

  35. Gutsch J, Berger H, Scholz G, et al.: [Prospective study in radically operated breast cancer with polychemotherapy, Helixor® and untreated controls]. Dtsch Z Onkol 21: 94-101, 1988. 

  36. Douwes FR, Wolfrum DI, Migeod F: [Results of a prospective randomized study: chemotherapy versus chemotherapy plus "biological response modifier" in metastasizing colorectal carcinoma]. Dtsch Z Onkol 18 (6): 155-64, 1986. 

  37. Piao BK, Wang YX, Xie GR, et al.: Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Res 24 (1): 303-9, 2004 Jan-Feb.  [PUBMED Abstract]

  38. Auerbach L, Dostal V, Václavik-Fleck I, et al.: Signifikant höherer anteil aktivierter NK-Zellen durch additive misteltherapie bei chemotherapierten mamma-Ca-patientinnen in einer prospektiven randomisierten doppelblinden studie. In: Scheer R, Bauer R, Becker H, et al.: Fortschritte in der Misteltherapie. Aktueller Stand der Forschung und klinischen Anwendung. Essen, Germany: KCV-Verlag, 2005, pp 543-54. 

  39. Matthes HF, Schad F, Buchwald D, et al.: Endoscopic ultrasound-guided fine-needle Injection of Viscum album L. (mistletoe; Helixor M) in the therapy of primary inoperable pancreas cancer: a pilot study. [Abstract] Gastroenterology 128 (Suppl 2): A-T988, A433-A434, 2005. 

  40. Beuth J, Schneider B, Schierholz JM: Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study. Anticancer Res 28 (1B): 523-7, 2008 Jan-Feb.  [PUBMED Abstract]

  41. Bar-Sela G, Haim N: Abnoba-viscum (mistletoe extract) in metastatic colorectal carcinoma resistant to 5-fluorouracil and leucovorin-based chemotherapy. Med Oncol 21 (3): 251-4, 2004.  [PUBMED Abstract]

  42. Salzer G, Danmayr E, Wutzholfer F, et al.: [Adjuvant Iscador® treatment of non-small cell bronchial carcinoma. Results of a randomized study]. Dtsch Z Onkol 23 (4): 93-8, 1991. 

  43. Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996. Complement Ther Med 6 (4): 172-7, 1998. 

  44. Bradley GW, Clover A: Apparent response of small cell lung cancer to an extract of mistletoe and homoeopathic treatment. Thorax 44 (12): 1047-8, 1989.  [PUBMED Abstract]

  45. Heiny BM, Albrecht V, Beuth J: Stabilization of quality of life with mistletoe lectin-1-standardized extract in advanced colorectal carcinoma. Onkologe 4 (Suppl 1): S35-9, 1998. 

  46. Sauer H: Quality of life stabilization with mistletoe-1-standardized extract in advanced colorectal carcinoma [Letter]. Onkologe 4: 1180, 1998.