Human/Clinical Studies
Iscador
Eurixor
Isorel
Helixor
Abnoba-viscum
Mistletoe has been evaluated as a treatment for cancer in numerous clinical studies.[1-33] Reviewed in [34-38] One ongoing phase II study in Israel involves carboplatin /gemcitabine in combination with mistletoe as a complementary treatment in patients with non-small cell lung cancer (ECOG-5597 and 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 trial is now closed and the data is being analyzed. Another United States 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 is closed.
The mistletoe extracts and products studied in clinical trials were Iscador, Eurixor, Helixor, Lektinol, Isorel, Abnoba-viscum,[39] and recombinant lectin ML-1 (refer to the tables at the end of this section).
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.
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 better 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.[21] 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 carefully measured 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 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.[24] 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.[40]
Three other studies of mistletoe were described in a single published report.[7] The patients in these studies were drawn from 10,226 cancer patients who were participants in a prospective study of the influence of self-regulation (i.e., the ability of a person to achieve a sense of well-being, inner equilibrium, a feeling of competence, and the ability to control stressful situations) on the incidence and course of cancer. Among these individuals, 1,668 patients who had been treated with Iscador and 8,475 patients who had received no mistletoe therapy were identified.
One of the three studies was a retrospective, prospective
matched-pair study of the effectiveness of Iscador as a treatment for cancer.[7] Among the patients who had been treated with Iscador and those who had not, 396 pairs of individuals were identified who were closely matched according to criteria of gender; year of birth within 3 years; year of cancer diagnosis within 3 years; type of cancer; stage of disease; type of metastasis, if present; and type(s) of conventional therapy received. These individuals had rectal cancer, colon cancer, breast cancer, stomach cancer, or lung cancer. It was reported that the mean survival time of the Iscador-treated patients was 39% longer than the mean survival time of the patients who had not been treated with mistletoe (mean survival times = 4.23 years and 3.05 years, respectively). This difference in survival was statistically significant. However, the retrospective nature of this study is a major weakness. Another weakness is the fact that Iscador use was incompletely ascertained. Only the actuality of mistletoe use (yes or no) and its overall duration of use were documented. No information was collected about the type of Iscador used (i.e., the host tree), the dose used, and whether there were any interruptions in use.
The second and third studies were prospective, randomized matched-pair studies (i.e., similar to randomized trials) that involved patients who were drawn from a group of 8,475 individuals who had not been treated with mistletoe.[7] From this group, two sets of matched pairs were created. One set contained 49 pairs of patients who had rectal cancer, colon cancer, stomach cancer, breast cancer, or lung cancer. The other set contained 17 pairs of individuals who had stage II or stage III breast cancer. These studies used the same matching criteria as the retrospective study. In the two sets, one member of each pair was randomly selected as a candidate for mistletoe therapy. These patients were advised to ask their doctor for Iscador treatment. Ultimately, only 39 individuals in the 49-pair set were treated with Iscador and eligible for analysis. All 17 pairs in the second set were eligible for analysis.
The mean survival time of the Iscador-treated patients in the 39-pair set was 42% longer than the mean survival time of the patients who were not treated with mistletoe (mean survival times = 3.49 years and 2.45 years, respectively). The mean survival time of the Iscador-treated patients in the 17-pair set was approximately twice that of the patients who did not receive mistletoe therapy (mean survival times = 4.79 years and 2.41 years, respectively). Both differences in survival were statistically significant.
These two randomized studies, however, had major weaknesses, including the recruitment of small numbers of patients and insufficient documentation of mistletoe use. As in the case of the retrospective study, only the actuality of mistletoe use (yes or no) and the overall duration of mistletoe treatment were ascertained. No information was collected on the type of Iscador used, the dose of Iscador used, and whether there were any interruptions in Iscador therapy.
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.
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.[41,42]
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.[43,44]
In another retrospective multicenter cohort study to determine safety and efficacy of Iscador as an adjuvant long-term treatment following surgery for multiple myeloma, 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 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.[40]
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.[4] Reviewed in [37] 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.[7] The same dose of Eurixor, however, has been used in other clinical studies, including studies in which benefit was reported.[1,3,22] In addition, both the dose and the duration of Eurixor treatment in this trial are consistent with those recommended by the manufacturer.[4]
A prospective, randomized phase II trial involved 45 patients who had noninvasive bladder cancer.[5] 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 eight 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 [1,3,35] Therefore, the dose of lectin administered to a person weighing 120 pounds (approximately 55 kilograms) 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 kilograms), 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. One other trial that used Eurixor without concurrent therapy involved 16 patients (seven women and nine men) with stage III and IV pancreatic cancer.[6]
Isorel
Only two trials of Isorel have been reported in the publicly available, online indexed peer-reviewed medical literature. In one study of 64 advanced colorectal cancer patients (Dukes C and D) patients 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.[45]
Helixor
In a three-arm randomized trial, 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.[19] In another three-arm randomized trial, 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 control patients were those randomly assigned to chemotherapy only; the treated patients were those randomly assigned to receive chemotherapy plus Helixor; and 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.[17]
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.[46]
Refer to the NCI's PDQ Clinical Trials Registry for a current list of active clinical trials involving the use of mistletoe in cancer treatment.
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
|
[28] |
Randomized trial |
Breast, stages I–III |
Unknown; 76; 79 |
Improved 14-y survival |
Unknown |
1iiA |
[28] |
Randomized trial |
Bronchial, operable |
50; 12, stage I only; 14, stage I only |
Improved median survival |
No |
1iiA |
[21] |
Randomized trial |
Lung, non-small cell, inoperable |
408; 105; 107f |
Subjective improvement in quality of life |
Yesg |
1iiA |
[30] |
Randomized trial |
Lung, non-small cell, stages I–IV |
218; 87; 96 |
Improved median survival, LN+ patients only |
No |
1iiA |
[24] |
Randomized trial |
Melanoma, stages II–III |
830; 102; 102 |
None |
No |
None |
[15,27,29] |
Randomized trial |
Stomach, stages I–IV |
359; 62, stages II–III only; 75, stages II–III only |
Improved median survival |
No |
1iiA |
[10] |
Nonrandomized
controlled
trial
|
Various types, no stage information |
Unknown; 72; 52 |
Improved 2-y survival, uterus and breast cancer |
Unknown |
2A |
[7] |
Prospective randomized matched-pair study |
Breast, stage III |
8,475h; 17i; 17i |
Improved mean survival |
Yes |
1iiA |
[7] |
Prospective randomized matched-pair study |
Various types, stages I–IV |
8,475h; 39i; 39i |
Improved mean survival |
Yes |
1iiA |
[9] |
Phase II trial |
Kidney, renal cell, stage IV |
14; 14; None |
None |
Yes |
3iiiA |
[7] |
Retrospective matched-pair, case-control study |
Various types, stages I–IV |
10,226h; 396i; 396i |
Improved mean survival |
Yes |
3iiiA |
[13] |
Nonconsecutive case series
|
Breast, stages I–IV |
1,314; 319, stages I–II only; 228, historical controls |
Improved 10-y survival |
Yes |
3iiiA |
[28] |
Nonconsecutive case series |
Bronchial, inoperable |
36; 36; 42, chemotherapy-treated historical controls |
Comparable survival |
No |
None |
[26] |
Nonconsecutive case series |
Bronchial, operable |
Unknown; unknown; unknown, historical controls |
Improved 5-y survival |
Unknown |
None |
[8,11] |
Nonconsecutive case series |
Cervical, stages I–III |
81; 81; 800, historical controls |
Improved 5-y survival |
No |
3iiiA |
[28] |
Nonconsecutive case series |
Colon, stages I–IV |
138; 47; 91 |
Improved 5-y survival |
No |
3iiiA |
[14] |
Nonconsecutive case series |
Lung, stages I–III |
77; 37; 40, historical controls |
Improved 6-y survival |
No |
3iiiA |
[23] |
Nonconsecutive case series |
Pancreas
|
292; 292; Various historical controls |
Improved median survival |
Yes |
3iiiA |
[28] |
Nonconsecutive case series |
Rectal, operable |
Unknown; 37; 34, historical controls |
Improved 5-y survival, LN+ patients only |
No |
None |
[16,28] |
Nonconsecutive case series |
Unknown metastatic (pleura carcinosis) |
168; 168; None |
Partial tumor response (number not specified) |
Yes |
None |
[12] |
Nonconsecutive case series |
Various female genital, stages I–IV |
87; 87; None |
Improved 5-y survival, stage III cervical, stages II–III
vaginal,
stage II
ovarian
|
Yes |
None |
[20] |
Case report
|
Lung, small cell, stage IV |
1; 1; None |
Partial response |
Yes |
None |
LN+ = lymph node-positive disease; No. = number; y = year.
|
aSee text and the NCI Dictionary 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
|
[5] |
Randomized trial |
Bladder, noninvasive |
45; 23; 22 |
None |
No |
1iiDi |
[1,3] |
Randomized trial |
Brain, glioma; 74% of patients, stages III–IV; 26% of
patients,
no stage
information
|
47, 20; 18 |
Improved survival,
stages
III–IV
patients
only
|
Yes |
1iiA |
[22] |
Randomized trial |
Breast, metastatic |
46; 21; 19f |
Improved quality of life |
Yesg |
1iiC |
[31,34] |
Randomized trial |
Colorectal, metastatic |
107; 38; 41 |
Improved quality of life |
Yes |
1iiA |
[4] |
Randomized trial |
Head and neck,
squamous
cell,
stages
I–IV
|
495; 235h; 242h |
None |
Yesh |
1iiA |
[6] |
Phase I/II trial |
Pancreas, stages III–IV |
16; 16; None |
Stabilized quality of
life |
No |
3iiiC |
No. = number.
|
aSee text and the NCI Dictionary 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 saline solution as a placebo.
|
gAll patients in this trial were treated with palliative chemotherapy (vindesine, epirubicin, and cyclophosphamide); chemotherapy and Eurixor were administered concurrently.
|
hThis 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
|
[19] |
Randomized trial |
Breast, stages I–III |
692; 192; 274 |
Improved survival |
Yes |
1iiA |
[17] |
Randomized trial |
Colorectal, metastatic
|
60; 20; 20 |
Improved mean survival |
Yes |
1iiA |
[18] |
Nonrandomized controlled trialf |
Colorectal, recurrent or metastatic |
40; 19; 20 |
Improved mean survival |
Yesg |
2A |
No. = number.
|
aSee text and the NCI Dictionary 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 planned as a randomized trial; however, the randomization scheme failed.
|
gThe patients received either chemotherapy only (n = 20) or chemotherapy plus Helixor (n = 20).
|
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
|
[32] |
Randomized trial |
PS76A2 (Lektinol) |
Breast |
272; Unknownf; unknowng |
Improved quality of lifeh |
Yes |
NoneI |
[45] |
Randomized trial |
Isorel |
Colorectal |
64; 50; 14 |
Improved survival and tolerance to either adjuvant or palliative treatment |
Yes |
1iiA |
[46] |
Nonrandomized controlled trial |
Abnoba-viscum Quercus |
Metastatic colorectal |
25; 25; none |
None |
Yes |
2Diii |
[39] |
Nonrandomized controlled trial |
Viscum fraxini-2 |
Hepatocellular carcinoma |
23; 23; none |
None |
No |
2Dii |
No. = number.
|
aSee text and the NCI Dictionary 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.
|
fPatients were randomly assigned to treatment with one of three doses (high, medium, or low) of an extract standardized on the basis of mistletoe lectin concentration.
|
gControl patients were treated with an unidentified placebo.
|
hQuality of life was assessed using the GLQ-8 global quality-of-life scales (eight self-assessment scales) and the Spitzer uniscale.
|
IResults have been reported in abstract form only; level of evidence scoring is not possible due to limited information.
|
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