Background
Methods
Design
Search strategy
Selection
Validity assessment and data abstraction
Results
Result of literature search
Characteristics of included clinical studies
Author, Year | Quality Criteria Fulfilled in StudiesI | Participants | ARII | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A) | B) | C) | D) | E) | F) | G) | H) | I) | J) | K) | |||
Tröger 2009 [47] | + | - | - | (+) | + | + | + | + | (+) | (+) | + | 95 | 6% |
Büssing 2008 [48] | +III | -III | -III | -III | (-)III | -III | (-)III | (-)III | (-)III | (-)III | -III | 65 | No data |
Grossarth 2008a [49] | + | + | - | (-) | + | (-) | + | (+) | + | + | - | 76 | 21% |
Grossarth 2008b [49] | + | + | - | (-) | + | + | + | (+) | + | + | - | 52 | 0% |
Grossarth 2007a [50] | + | + | - | (-) | + | (-) | + | (+) | + | + | - | 50 | 16% |
Grossarth 2007b [50] | + | + | - | (-) | + | (-) | + | (+) | + | + | - | 48 | 17% |
Grossarth 2007c [51] | + | + | - | (-) | + | + | + | (+) | + | + | - | 38 | 0% |
+ | + | - | (-) | + | (-) | + | (+) | + | + | - | 118 | 36% | |
Semiglasov 2006 [54] | + | - | (+) | (+) | + | + | + | + | + | + | + | 352 | 4% |
Auerbach 2005 [55] | + | - | (+) | (+) | + | - | + | (+) | + | (+) | + | 23 | 30% |
Piao 2004 [56] | + | + | - | (-) | + | + | + | (+) | + | + | + | 233 | 4% |
Semiglasov 2004 [57] | + | - | (+) | (+) | + | + | + | + | + | + | + | 272 | 4% |
Borrelli 2001 [58] | + | - | (+) | (+) | + | + | (+) | + | (-) | (+) | - | 30 | 0% |
Grossarth 2001a [59] | + | + | - | (-) | + | + | + | (-) | + | + | - | 34 | 0% |
Grossarth 2001b [59] | + | + | - | (-) | + | (-) | + | (-) | + | + | - | 98 | 20% |
Kim 1999 [60] | + | - | - | - | (-) | - | (+) | (+) | (-) | (-) | - | 30IV | 13% |
Heiny 1991 [61] | + | - | (-) | (-) | + | (+) | + | (+) | + | + | - | 46 | 13% |
Gutsch 1988 [62] | + | - | - | (-) | + | (-) | + | + | (+) | + | - | 692 | 20% |
Lange 1985 [63] | + | + | - | (-) | + | (-) | + | (+) | + | + | - | 68 | 35% |
Author, Year | Quality Criteria Fulfilled in StudiesI | Participants | ARII | Design/control for confounding | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A) | B) | C) | D) | E) | F) | G) | H) | I) | J) | K) | ||||
Grossarth 2008c [49] | (+) | + | - | (-) | + | + | + | (+) | + | + | - | 200 | 5% | Prospective pair-matching |
Grossarth 2008d [49] | (+) | + | - | (-) | + | (-) | + | (+) | + | + | - | 282 | 27% | Prospective pair-matching |
Loewe-Mesch 2008 [64] | - | - | - | (-) | + | (-) | + | + | (+) | + | - | 82 | 20% | Self-selected treatment allocation, no adjustment |
Grossarth 2007d [50] | (+) | + | - | (-) | + | (-) | + | (+) | + | + | - | 198 | 24% | Prospective pair-matching |
Grossarth 2007e [50] | (+) | + | - | (-) | + | + | + | (+) | + | + | - | 132 | 6% | Prospective pair-matching |
Grossarth 2007f [51] | (+) | + | - | (-) | + | + | + | (+) | + | + | - | 212 | 4% | Prospective pair-matching |
Grossarth 2007g [51] | (+) | + | - | (-) | + | + | + | (+) | + | + | - | 140 | 6% | Prospective pair-matching |
(+) | + | - | (-) | + | (-) | + | (+) | + | + | - | 210 | 20% | Prospective pair-matching | |
Büssing 2005 [65] | (-) | - | - | (-) | + | + | (+) | (+) | (+) | + | + | 105 | 7% | Comparison of two different hospitals. Pair-matching for analysis |
Grossarth 2001c [59] | (+) | + | - | (-) | + | + | + | - | + | + | - | 792 | 4% | Prospective pair-matching |
Salzer 1987 [66] | (+) | - | - | (-) | + | - | + | - | - | (+) | - | 155 | not shown | Alternating treatment allocation |
Fellmer 1966 [67] | - | - | - | (-) | + | - | + | + | - | - | - | 924 | 15% | Treatment allocation by neutral attending physician |
Majewski 1963 [68] | (+) | - | - | (-) | + | - | + | - | - | - | - |
III
| not shown (15%)IV | Alternating treatment allocation |
Retrolective pharmaco-epidemiological cohort studies | ||||||||||||||
Beuth 2008 [69] | - | (+) | - | - | (-) | - | (+) | (-) | (+) | (+) | + | 681 |
V
| Multivariate adjustment only for one main outcome ("complaints") |
Bock 2004 [70] | - | (+) | - | - | (-) | - | (+) | + | (+) | (+) | + | 1442 |
V
| Multivariate adjustment |
- | (+) | - | - | (-) | - | (+) | + | (+) | (+) | + | 689 |
V
| Propensity score adjustment |
Site | Stage | Intervention (evaluable patients) | Survival Outcomes | Author, year, reference | ||||
---|---|---|---|---|---|---|---|---|
Years (median) | Hazard ratio | 5-year survival and others | P-value | 95% CI | ||||
Randomized controlled trials
| ||||||||
Breast | T1a-3, N0, M0 | Iscador (38) | 14.8 | 0.65 | 0.2 | 0.34–1.25 | ||
None (38) | 13.8 | |||||||
IIIA–IIIB | Iscador (17) | 6.3 | 0.46 | 0.13 | 0.16–1.31 | |||
None (17) | 2.3 | |||||||
T1-3, N0-3, M0, local recurrence | Surgery, radiationI, Helixor (192) | Not applicableII | 69.1% 5-year survival | 0.048 | Gutsch 1988 [62] | |||
Surgery, radiationI, CMF (177) | 67.7% 5-year survival | 0.025 | ||||||
Surgery, radiationI (274) | 59.7% 5-year survival | |||||||
Breast, others | All stages | Iscador (39) | 3.5 (mean) | 0.04 | Grossarth 2001b [59] | |||
None (39) | 2.5 (mean) | |||||||
Cervix | IVA-B | Iscador (19) | 1.83 | 0.46 | 0.12 | 0.18–1.21 | Grossarth 2007c [51] | |
None (19) | 1.92 | |||||||
Uterus | IA-C | Iscador (30) | 6.29 | 0.36 | 0.014 | 0.16–0.82 | Grossarth 2008a [49] | |
None (30) | 5.17 | |||||||
IVA-B | Iscador (26) | 1.5 | 1 | 0.99 | 0.46–2.16 | Grossarth 2008b [49] | ||
None (26) | 2.0 | |||||||
Ovary | IA–IC | Iscador (21) | 6.75 | 0.40 | 0.058 | 0.15–1.03 | Grossarth 2007a [50] | |
None (21) | 5.58 | |||||||
IV | Iscador (20) | 2.75 | 0.33 | 0.033 | 0.12–0.92 | Grossarth 2007b [50] | ||
None (20) | 1.58 | |||||||
Non-randomized controlled studies
| ||||||||
Breast | T1-3, N0, M0 | Iscador (84)III | 11.75 | 0.42 | 0.0002 | 0.27–0.68 | ||
None (84) | 10.13 | |||||||
Local recurrence, N0, M0 | Iscador (29)IV | 5.17 | 0.0025 | |||||
None (29) | 4.33 | |||||||
T1-4, N>1, M0 | Iscador (38)IV | 4.04 | 0.0516 | Ø same study | ||||
None (38) | 3.17 | |||||||
TX, NX, M1 | Iscador (53)IV | 3.08 | 0.0056 | Ø same study | ||||
None (53) | 2.17 | |||||||
I–III | Iscador, (76) | 29% alive 1985, after 11–14 years | not shown | Salzer 1987 [66] | ||||
Radiation, hormone (79) | 24% alive 1985, after 11–14 years | |||||||
Cervix | IB-IVA | Iscador (102)III | 7.17 | 0.41 | <0.0001 | 0.27–0.63 | Grossarth 2007f [51] | |
None (102) | 5.92 | |||||||
IV | Iscador (66)III | 2.33 | 0.54 | 0.015 | 0.32–0.89 | Grossarth 2007g [51] | ||
None (66) | 1.83 | |||||||
I–III | Radiation, Iscador (81) | 83% 5-year survival | 0.05 | Fellmer 1966 [67] | ||||
Radiation (709) | 69% 5-year survival | |||||||
Uterus | IIIA–IVB | Iscador (95)III | 2.75 | 0.61 | 0.023 | 0.39–0.93 | Grossarth 2008c [49] | |
None (95) | 1.67 | |||||||
IA-C | Iscador (103)III | 8.75 | 0.41 | <0.0001 | 0.26–0.63 | Grossarth 2008d [49] | ||
None (103) | 6.67 | |||||||
Ovary | IA–IC | Iscador (75)III | 6.83 | 0.47 | 0.0002 | 0.31–0.69 | Grossarth 2007d [50] | |
None (75) | 5.83 | |||||||
IV | Iscador (62)III | 1.79 | 0.62 | 0.077 | 0.37–1.05 | Grossarth 2007e [50] | ||
None (62) | 1.17 | |||||||
Genital | All stages | SurgeryI, radiationI, Iscador (155) | Disease-specific survival partly improved | not shown | Majewski 1963 [68] | |||
SurgeryI, radiationI,(not shown) | ||||||||
Retrolective pharmaco-epidemiological cohort studies
| ||||||||
Breast | I–III | Conventional therapy, Iscador (710) | 0.46 | 0.038 | 0.22–0.96 | Bock 2004 [70] | ||
Conventional therapy (732) | ||||||||
I–IV | Conventional therapy, Eurixor (219) | No difference observedV | ||||||
Conventional therapy (470) |
Site | Stage | Intervention (evaluable patients) | Outcome | P-value | 95% CI | Author, year, reference |
---|---|---|---|---|---|---|
R
EMISSION
| ||||||
Randomized controlled trials
| ||||||
Breast, ovary, lung | T1–4, N0–3, M0–1 | ChemotherapyI, Helixor A (115) | Remission rate: no difference | Piao 2004 [56] | ||
ChemotherapyI, Lentinan (109) | ||||||
Ovary, others | Inoperable | Radiation, cisplatin, holoxan, Helixor (23) | 10% complete remission 48% partial remission 5% progress | Lange 1985 [63] | ||
Radiation, cisplatin, holoxan (21) | 17% complete remission 48% partial remission 4% progress | |||||
Pleural effusionII | Advanced | Helixor (11) | 82% complete remission 9% partial remission | <0.05 III | Kim 1999 [60] | |
Doxycycline, meperidine, lidocaine (15) | 40% complete remission 27% partial remission | |||||
D
ISEASE-FREE INTERVAL, TIME TO EVENT, RECURRENCE
(H
AZARD RATIO
)
| ||||||
Randomized controlled trials
| ||||||
Breast | T1a-3, N0, M0 | Iscador (38) | Time to local recurrences: 0.44 lymphatic metastases: 0.27 distant metastases: 0.50 all events (incl.death) 0.65 | 0.18 0.0048 0.061 0.012 | 0.14–1.44 0.11–0.67 0.24–1.03 0.47–0.91 | |
None (38) | ||||||
Non-randomized controlled trials
| ||||||
Breast | T1–3, N0, M0 | Iscador (84) | Time to local recurrences: 0.42 lymphatic metastases: 0.22 distant metastases: 0.36 all event (incl.death) 0.66 | 0.21–0.83 0.10–0.47 0.21–0.62 0.55–0.79 | ||
None (84) | ||||||
Cervix | IB-IVA | Iscador (102) | Time to local recurrences: 1.42 lymphatic metastases: None distant metast.:1 in Iscador group all event (incl.death) 0.32 | 0.61 n.a. n.a. <0.0001 | 0.37–5.39 n.a. n.a. 0.22–0.48 | Grossarth 2007f [51] |
None (102) | ||||||
Retrolective pharmaco-epidemiological cohort study
| ||||||
Breast | I–III | Conventional therapy, Helixor (167) | Recurrence, metastases, reoperation: no difference | Beuth 2008 [69] | ||
Conventional therapy (514) | ||||||
I–III | Conventional therapy, Iscador (710) | Recurrence: 0.98 Dist. metast. 0.65 | 0.947 0.172 | 0.60–1.62 0.35–1.21 | Bock 2004 [70] | |
Conventional therapy (732) | ||||||
I–IV | Conventional therapy, Eurixor (219) | Time to relapse: 0.28 | 0.012 | 0.10–0.76 | ||
Conventional therapy (470) |
Site | Stage | Intervention (evaluable patients) | Reduction of side effects of chemotherapy, radiation or surgery | QoL (*during chemotherapy, radiation) | Author, year, reference | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Outcome | P-value | Measurement scale and outcome | P-value | 95% CI | ||||||||
Randomized controlled trials
| ||||||||||||
Breast | T1–3, N0–2, M0 | CAF, Iscador or Helixor (59) | Neutropenia | 15% | 0.195 | EORTC QLQ-C30* (Pain*, diarrhoea*, role*, insomnia*, nausea/vomiting*) | 0.0438 to 0.0003 | Tröger 2009 [47] | ||||
CAF (30) | 27% | |||||||||||
No data | (F)EC, Iscador M (32) | EC-associated inhibition of granulocyte function: no difference. Reduction of EC-related side effects (nausea, constipation, pain, stomatitis). Lymphocytes, retching, emesis: no difference | >0.27 | EORTC QLQ-C30*, BR 23*, Rhodes Index*: no difference | No data | No data | Büssing 2008 [48] | |||||
(F)EC (33) | "significant" | |||||||||||
T1a-3, N0, M0 | Iscador (38) | Self-regulation questionnaire, Hazard-ratio | 0.35 | 0.05–0.60 | ||||||||
None (38) | ||||||||||||
T1–3, N0-N+, M0 | CMF, Lektinol 15 ng ML (169) | Haematological parameters, hospitalization, paracetamol, metoclopramid: no difference. Leucopenia ↓ (trend) | FACT-G* ↑ 4.4 | GLQ-8* sum ↓ 28.9 | Spitzer uniscale* ↓ 12.2 | KPS* No difference | <0.0001 | Semiglasov 2006 [54] | ||||
CMF, placebo (168) | FACT-G* ↓ 5.11 | GLQ-8* sum ↑ 94.8 | Spitzer uniscale* ↑ 10.8 | |||||||||
T1–2, N0–1, M0 | CMF, radiation, Helixor A (11) | CMF-induced NK-cell decrease ↓ SCE-increase ↓ other immune markers: no difference | 0.005 n.s. | EORTC QLQ-C30* | No difference, data not shown | not shown | Auerbach 2005 [55] | |||||
CMF, radiation, placebo (9) | ||||||||||||
T1–3, N0-N+, M0 | CMF, Lektinol 5 ng ML (66) | Haematological parameters, hospitalization, paracetamol, metoclopramid: no difference. immune markerers: CD4, CD4/CD8, NK-cell-activity: significant ↑ | GLQ-8* sum No difference | Spitzer uniscale* No data | QLQ C-30* No difference | <0.05 | Semiglasov 2004 [57] | |||||
CMF, Lektinol 15 ng ML (65) | GLQ-8* sum Superior 60,8mm | Spitzer uniscale* Superior 16,4 mm | ||||||||||
CMF, Lektinol 35 ng ML (64) | GLQ-8* sum No difference | Spitzer uniscale* No data | ||||||||||
CMF, placebo (66) | ||||||||||||
IIIA–IIIB | Iscador (17) | Self-regulation questionnaire (score 1–6) | 2.92 → 3.7 | 0.13 | Grossarth 2001a [59] | |||||||
None (17) | 2.87 → 2.99 | |||||||||||
IV | Iscador spezial (20) | Spitzer score questionnaire | ~5 → 7.2 | <0.05 | Borrelli 2001 [58] | |||||||
Placebo (10) | ~5.2 → 4.8 | |||||||||||
Advanced | VEC, Eurixor (21) | Leukopenia ↓ Platelets: no difference | ≤ 0.001 | QoL index* (superior) | Anxienty scale* (superior) | ≤ 0.01 | Heiny 1991 [61] | |||||
VEC, placebo (19) | ||||||||||||
Breast, others | All stages | Iscador (39) | Self-regulation questionnaire (score 1–6) | 3.41 → 3.87 | 0.02 | Grossarth 2001b [59] | ||||||
None (39) | 3.85 → 3.62 | |||||||||||
Breast, ovary, lung | T1–4, N0–3, M0–1 | ChemotherapyI, Helixor A (115) | Chemotherapy-related adverse events 28 | not shown | FLIC-score* ↑ 9 | TCM-score* ↑ -1 | KPS* increase in % of patients 50% | FLIC 0.014 TCM 0.0007 KPS 0.002 | Piao 2004 [56] | |||
ChemotherapyI, Lentinan (109) | Chemotherapy-related adverse events 77 | FLIC-score* ↑ 4,7 | TCM-score* 0 | KPS* increase in % of patients 32% | ||||||||
Ovary | IA–IC | Iscador (21) | Self-regulation questionnaire, (score 1–6) median difference | 0.58 | 0.0002 | 0.30–0.90 | Grossarth 2007a [50] | |||||
None (21) | ||||||||||||
Ovary, others | Inoperable | Radiation, cisplatin, holoxan, Helixor (23) | Nausea ↓, vomiting ↓, depression of leucopoiesis ↓ | 0.005, 0.08, 0.003 | KPS* | 67% → 76% (p = 0.0008II) | not shown | Lange 1985 [63] | ||||
Radiation, cisplatin, holoxan (21) | 70% → 74% (p = 0.12II) | |||||||||||
Cervix | IVA-B | Iscador (19) | Self-regulation questionnaire, (score 1–6) median difference | 0.7 | 0.014 | 0.15–1.05 | Grossarth 2007c [51] | |||||
None (19) | ||||||||||||
Uterus | IA-C | Iscador (30) | Self-regulation questionnaire, (score 1–6) median difference | 0.4 | 0.0012 | 0.15–0.70 | Grossarth 2008a [49] | |||||
None (30) | ||||||||||||
Non-randomized controlled studies
| ||||||||||||
Breast | T1–3, N0, M0 | Iscador (84) | Self-regulation questionnaire Hazard-ratio | 0.20 | 0.031 | 0.00–0.35 | ||||||
None (84) | ||||||||||||
I–II | Surgery, CMF/EC, Iscador (33) | CMF/EC-induced lymphocyte decrease ↑, platelet decrease ↓ | n.s, 0.01 | EORTC QLQ-C30*, BR 23* | Reduced increase of nausea/vomiting, general side effects of CMF/EC | 0.02 0.02 | Loewe-Mesch [64] | |||||
Surgery, CMF/EC (33) | ||||||||||||
Breast (suspected) | Surgery, Iscador M spezial (47) | Prevention of surgery-associated inhibition of granulocyte function (PMA- and E.coli-stimulated oxidative burst) | <0.0001,<0.001 | Büssing 2005 [65] | ||||||||
Surgery (51) | ||||||||||||
Ovary | IA–IC | Iscador (75) | Self-regulation questionnaire, (score 1–6) median difference | 0.30 | <0.026 | 0.10–0.60 | Grossarth 2007d [50] | |||||
None (75) | ||||||||||||
Cervix | IB-IVA | Iscador (102) | Self-regulation questionnaire, (score 1–6) median difference | 0.25 | <0.0005 | 0.15–0.35 | Grossarth 2007f [51] | |||||
None (102) | ||||||||||||
Uterus | IA-C | Iscador (103) | Self-regulation questionnaire, (score 1–6) median difference | 0.65 | <0.0005 | 0.4–0.95 | Grossarth 2008d [49] | |||||
None (103) | ||||||||||||
Retrolective pharmaco-epidemiological cohort study
| ||||||||||||
Breast | I–III | Conventional therapy, Helixor (167) | Odds ratio for occurrence of disease- or treatment associated symptoms: 0.508 | 0.319–0.811 | Beuth 2008 [69] | |||||||
Conventional therapy (514) | ||||||||||||
I–III | Conventional therapy, Iscador (710) | Adverse drug reactions ↓, Odds ratio: 0.47 | 95% CI 0.32–0.67 | Odds ratio for being symptom-free 3.56 (vomiting, headache, exhaustion, depression, concentration, sleep, dizziness, irritability) ↑ | 2.03–6.27 | Bock 2004 [70] | ||||||
Conventional therapy (732) | ||||||||||||
I–IV | Conventional therapy, Eurixor (219) | Symptom mean score improved (nausea, appetite, stomach pain, tiredness, depression, concentration, irritability, sleep) | <0.0001 | |||||||||
Conventional therapy (470) |
Author, Year | TreatmentI | SiteII | OutcomeIII | NIV | Quality Criteria FulfilledVI | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Preparation | Injection site | Dosage | Escalating dosage | Duration | CR | PR | NC | PD | QoL | L | M | N | O | P | Q | |||
Breast, Ovary, CIN
| ||||||||||||||||||
Helixor (& gemcitabine) | sc | Up to 250 mg, daily | Yes | 9 w | Breast, others | 0% | 10% | 47% | 43% | 27 | (+) | + | + | -V | (+) | (+) | ||
Schink 2006 [45] | Helixor (& surgery) | sc | 3/week, varying individually | Yes | Up to 2 years | Breast, colon | - | - | - | - | ↗IIIa | 40 | + | + | (+) | (+)V | (+) | - |
Schöffski 2004 [32] | Aviscumine | iv | 10 – 6400 ng/kg, 2/w | Yes | 3–24 w, median 6 w | Ovary, breast, others | 0% | 0% | 30% | 70% | 37 | + | (+) | + | + | + | + | |
Mahfouz 1999 [74] | Viscum fraxini | sc or it | 1 × 45 mg/w | No | 16–136 w | Breast | 8% | 54% | 35% | 4% | ↗ | 26 | (+) | (+) | + | (+) | + | + |
Mahfouz 1998 [75] | Abnobaviscum Fr | sc | 1 × 45 mg/w | No | 17 w | Breast | 0% | 44% | 33% | 22% | ↗ | 9 | - | (-) | (+) | - | - | (+) |
Finelli 1998 [76] | Lektinol | sc | 2,5 μl/kg, 2/w | No | Up to 12 w | Breast, others | - | - | - | - | ↗ | 884 | + | + | + | - | + | + |
Portalupi 1995 [77] | Iscador M | sc | 2 × 1 ng MLI/kg bw × w | No | 16 w | CIN I–III | 41% | 27% | 27% | 5% | 22 | + | + | + | + | + | (+) | |
Malignant effusion
| ||||||||||||||||||
Bar-Sela 2006 [46] | Iscador M | ip | 10 mg | No | repeatedly | Ascites (ovary, others) | Increase of interval between two successive paracenteses from 7 to 12 days, p = 0.001IIIb | ↗IIIc | 23 | (+) | (+) | + | (+) | + | + | |||
Werner 1999 [78] | Abnobaviscum Fr | ipl | 1 × 75 mg/w | No | 3–8 w | Pleural effusion (breast, others) | 88% | ↗ | 32 | + | + | + | - | (+) | (+) | |||
Stumpf 1994 [79] | Helixor A, M or P | ipl | 100–1000 mg | Yes | repeatedly | Pleural effusion (breast, others) | 61% | 11% | 22% | 18 | + | + | + | (+) | + | + | ||
Friedrichson 1995 [80] | Helixor A, M | ip | 100–1000 mg, 2/w | Yes | repeatedly | Ascites (ovary, others) | 70% | ↗ | 12 | (+) | (-) | + | - | (-) | + |
Controlled studies
Single-arm studies
Quality assessment
Characteristics of the preclinical studies
Tumour cell | VAE | Result | Reference | |
---|---|---|---|---|
Breast cancer
| ||||
MFM-223 | Iscador Qu, M, A Iscador P ML I | IC50 | 0.05–0.12 mg/ml 1.89 mg/ml 38 ng/ml | [22] |
Iscador M, Qu, Abnobaviscum Fr | Inhibition of proliferation | 0.1–1 mg/ml 0.01–1 mg/ml | [81] | |
KPL-1 | Iscador Qu, M, A Iscador P ML I | IC50 | 0.1–0.3 mg/ml 1.94 mg/ml 141 ng/ml | [22] |
Iscador M, Qu, Abnobaviscum Fr | Inhibition of proliferation | 1 mg/ml 0,1–1 mg/ml | [81] | |
Iscucin® A, M, P, C, Po, T, Qu, S | Cytotoxicity | 0.1 mg/ml | [82] | |
Iscador M ML I | No stimulation of cell proliferation | 0.05–5 ng ML/ml 0.01–5 ng/ml | [83] | |
MCF-7 | Iscador Qu, M, A Iscador P ML I | IC50 | 0.09–0.12 mg/ml 1.61 mg/ml 410 ng/ml | [22] |
Lektinol | IC50 | >10 ng ML I/ml | [84] | |
Iscador Qu, M, P (max. 1 or 1.5 mg/ml) | Inhibition of S-phase progression Induction of apoptosis | |||
Iscador M Iscador P ML I Iscador Qu | IC50 No influence | 185 μg/ml no activity 0.003 μg/ml 0.0015–15 μg/ml | ||
Viscotoxin isoforms (A1, A2, A3, B, 1-PS) Viscotoxin isoform U-PS | GI50 LC50 | 0.02–0.8 μg/ml 0.6 to >1 μg/ml no activity | [90] | |
ML I A chain | Inhibition of proliferation | 0.5 μg/ml | [91] | |
ML I, ML II, ML III | Inhibition of proliferation | 1–10 ng/ml | [91] | |
TNF & ML I (100 ng/ml) | Potentiation of TNF-cytotoxicity | [92] | ||
Lektinol | IC50 | 0.003 μg/ml | [93] | |
Helixor P ML I | IC50 | > 150 μg/ml 0.086 μg/ml | [94] | |
Iscucin M, P, C, Po, T, Qu, S Iscucin A, Pi | Cytotoxicity | 0.1 mg/ml no activity | [82] | |
MCF-7/ADR | Lektinol | IC50 (SRB assay) | 0.3 E-4 μg/ml | [93] |
MAXF 401NL | Helixor P ML I | IC50 | 0.66 μg/ml 0.003 μg/ml | [94] |
Iscador M Iscador P ML I Iscador Qu | IC50 >70% growth inhibition | < 3 μg/ml no activity 0.353 E-4 μg/ml 10 μg/ml | ||
MAXF 401 | Lektinol | IC50 | < 0.1 E-4 μg/ml | [93] |
MAXF 1162 | Lektinol | IC50 | < 0.1 E-4 μg/ml | [93] |
MAXF 449 | Lektinol | IC50 | 0.2 E-4 μg/ml | [93] |
MAXF MX1 | Lektinol | IC50 | < 0.1 E-4 μg/ml | [93] |
MDA-MB-231 | Lektinol | IC50 | 0.7 E-4 μg/ml | [93] |
Helixor P ML I | IC50 | 135 μg/ml 0.041 μg/ml | [94] | |
MDA-MB-468 | Helixor P ML 1 | IC50 | 47 μg/ml 0.006 μg/ml | [94] |
MDA-MB-486-HER2 | Iscador M | Inhibition of epidermal growth factor-induced proliferation | 0.5 μg/ml | [95] |
Colo-824 | Iscador M ML I | No stimulation of cell proliferation | 0.05–5 ng ML/ml 0.01–5 ng/ml | [83] |
HCC-1937 | Iscador Qu, M, A Iscador P ML I | IC50 | 0.1 to 0.3 mg/ml 2.14 mg/ml 320 ng/ml | [22] |
Iscucin A, M, P, C, Po, T, Qu, S | Cytotoxicity | 0.1 mg/ml | [82] | |
BT474 | Helixor M, A | Cytotoxicity (WST-1) | Maximum (80 and 100%) with 25 mg/ml | [96] |
Primary breast cancer | Iscador M, Qu Abnobaviscum Fr | Mitochondrial activity (MTT) | 50–80% with 0.1–0.001 mg/ml | [81] |
Abnobaviscum M | Inhibition of proliferation | 0.5–50 μg/ml | [97] | |
ML I | Inhibition of proliferation | 1–50 ng/ml | ||
T47D | ML I, II, III | IC50 | > 0.1 – 1 ng/ml | [99] |
ML I A-chain | Inhibition of proliferation | 10 ng/ml | [91] | |
BT549 | ML I A-chain | Inhibition of proliferation | 500 ng/ml | [91] |
HBL100 | ML I A-chain | Inhibition of proliferation | 100 ng/ml | [91] |
Breast cancer cells | ML II, ML III, viscotoxins | Cytotoxicity | [100] | |
Ovarian cancer
| ||||
OVXF 1619L | Helixor P ML I | IC50 | 119 μg/ml 0.100 E-3 μg/ml | [94] |
OVXF 899L | Helixor P ML I | IC50 | >150 μg/ml 0.229 μg/ml | [94] |
SKOV-3 (HER-2 expression) | Recombinant ML I | IC50 Induction of apoptosis | 0.033 ng/ml | [101] |
OVCAR3 | Iscador Qu, M (max. 1 or 1.5 mg/ml) | Inhibition of S-phase progression, Induction of apoptosis | No clear effect | [87] |
OVXF 899 | Lektinol | IC50 | 0.3 E-3 μg/ml | [93] |
OVXF 1353 | Lektinol | IC50 | 0.01 μg/ml | [93] |
OVXF 1023 | Lektinol | IC50 | < 0.1 E-4 μg/ml | [93] |
SKOV3 | Lektinol | IC50 | < 0.1 E-4 μg/ml | [93] |
Primary ovarian cancer | Abnobaviscum M | Inhibition of proliferation | 5 μg/ml | [97] |
Uterine cancer
| ||||
UXF 1138L | Iscador M Iscador P ML I Iscador Qu | IC50 Growth inhibition >30% | 6.8 μg/ml No activity 0.16 E-4 μg/ml 15 μg/ml | |
UCL SK-UT-1B | Helixor P ML I | IC50 | > 150 μg/ml 0.038 μg/ml | [94] |
SK-UT-1B | Lektinol | IC50 | 0.6–5.5 ng ML I/ml | [84] |
ML I | Inhibition of proliferation | 0.5–500 ng/ml | ||
Iscador M ML I | No stimulation of cell proliferation | 0.05–5 ng ML/ml 0.01–5 ng/ml | [83] | |
SK-UT-1 | ML I | Inhibition of proliferation | 0.5–500 ng/ml | |
MES-SA | ML I | Inhibition of proliferation | 0.5–500 ng/ml | |
Primary uterus cancer | Abnobaviscum M | Inhibition of proliferation | 5–50 μg/ml | [97] |
Vulvar cancer
| ||||
SK-MLS-1 | Lektinol | IC50 | 2 to >5 ng ML I/ml | [84] |
ML I | Inhibition of proliferation: | 0.5–500 ng/ml | ||
Iscador M ML I | No stimulation of cell proliferation | 0.05–5 ng ML/ml 0.01–5 ng/ml | [83] | |
Cervical cancer
| ||||
HeLa | TNF & ML I (100 ng/ml) | Potentiation of TNF-cytotoxicity | [92] | |
ML I | Inhibition of protein synthesis | 100 μg/ml | ||
Protein fractions | Complete inhibition of DNA-, RNA-synthesis Proliferation | 1 μg/ml no effect | [104] | |
Viscotoxins | IC50 | 0.2–1.7 μg/ml | [105] | |
Helixor M | Growth inhibition | ≥ 0.01 mg/ml | [106] | |
Isorel® | Cytotoxicity | 30 μg/μl | [107] | |
Isorel A, M, P, ML I | Cytotoxicity | > 1 μl/ml > 1 μg/ml | [108] | |
Iscador M Helixor M VAE M | LC50 | 16 μg/ml 35,4 μg/ml 3,9 μg/ml | ||
Iscador M, Qu Abnobaviscum Fr | Growth inhibition | 0.1–1 mg/ml 0.01 mg/ml | [81] |
Animal studies
Tumour, site | Animal | VAE, application and dosage | Tumour growth T/C | Survival ILS | Other outcomes | Reference |
---|---|---|---|---|---|---|
Human breast
|
Mice
| |||||
MAXF 449, sc | Nude mice | Local Abnobaviscum Qu 8 or 4 or 2 mg/kg, it, qd * 3 | 6 to 20% | [116] | ||
Systemic Abnobaviscum Qu 8 mg/kg, it, qd * 3 | 78% | |||||
MAXF 449, sc | Nude mice | Abnobaviscum M 8 mg/kg, sc, qd * 3 * 2 w | 68% | [116] | ||
BT474, sc | Mice (BALB/c) | Helixor M or A 5 mg, it, qd * 3 * 2 w | 29 to 52% | [96] | ||
Murine breast
| ||||||
Carcinoma, sc, iv | Mice (CBA/HZgr) | Isorel M, 3 mg, sc, qod * 21 | No difference | Lung-metastases: VAE vs. control: 13.4 vs. 37.5 | [117] | |
Carcinoma, sc | Mice (CBA/HZgr) | Isorel M, 1400 mg/kg, 2 w | 20% | [118] | ||
Carcinoma, sc | Mice (CBA/HZgr) | Isorel M, 140 mg/kg | Recurrence after resection, VAE vs. control: 47% vs. 78% | [118] | ||
Carcinoma, iv | Mice (CBA/HZgr) | Isorel M, 140 mg/kg, ip | 52 lung-metastases | [118] | ||
Endoxan, 50 mg/kg | 23 lung-metastases | |||||
Isorel M, 140 mg/kg & Endoxan 50 mg/kg | 10 lung-metastases | |||||
Control | 76 lung-metastases | |||||
C3H adenocarcinoma, 16/C | Mice (B6C3F1) | Iscador M, 50 or 100 mg/kg, ip, qd, day 1–14 | 28% | 15 to 20% | [119] | |
RC adenocarcinoma, sc | Mice (DBA) | VAE I, sc | 20 to 40% | [111] | ||
ECa, ip | Mice (NMRI) | VAE (supracritical CO2 extraction), 2 mL/kg, ip, qd, starting day -7, day 0, or day 7 | 65 to 100%II | [120] | ||
ECa, ip | Mice (BALB/c) | Iscador, 15 μg, ip, day -1 | 108% | [121] | ||
Sodium caseinate & Iscador, 15 μg, ip, day -1 | no death | |||||
Sodium caseinate, day -1 | 0% | |||||
ECa, ip | Mice (BALB/c) | Iscador, 15 μg, ip, day 6 | 82% | [121] | ||
Sodium caseinate, day 6 | 7% | |||||
ECa, ip | Mice (BALB/c) | Iscador-activated macrophages, ip, day 6 | 49% | [121] | ||
Non-activated macrophages, ip, day 6 | 4% | |||||
ECa, ip | Mice (BALB/c) | Iscador activated macrophages, ip, day 6, 10, 14 | 98% | [121] | ||
Non-activated macrophages, ip, day 6, 10, 14 | 9% | |||||
ECa, sc | Mice (BALB/c) | Iscador, 15 μg, it, day 7 | Severe necrosis, infiltration of lymphocytes and macrophages | [122] | ||
ECa, sc | Mice (Swiss) | Iscador M, 1.66 mg, im, qod * 5 or 10 | 3 to 10% | [123] | ||
ECa, ip | Mice (Swiss) | Iscador M, 1.66 mg, ip, qod * 10 | 76% | [123] | ||
ECa, ip | Mice (Swiss) | Iscador M, 25 or 50 mg/kg, ip, qd * 14 | 69 to 97% | No tumour-free mice | [119] | |
ECa, ip | Mice (Swiss) | Iscador M, sc, cumulative dose 4, 5, 150, or 200 mg | -4 to 0% | [124] | ||
ECa, sc | Mice | VAE, it, 0.1–0.2 ccm, qod * 6–10 | Complete remission & no recurrence: 27% | |||
Murine breast
|
Rats
| |||||
Walker carcinosarcoma 256; sc | Rats (Sprague Dawley) | Iscador M, sc, cumulative dose 11, 16, 500, or 750 mg or combination of Iscador M, sc, cumulative dose 11 or 500 mg & Cetraria praeparata, cumulative dose 3 or 164 mg | 93 to 115% | -16 to 8% | [124] | |
Dunning DMBA-5A; sc | Rats | Iscador M, 2.5–15 mg, ip, qd | No difference | Less tumour viability | [127] | |
Walker carcinosarkoma 256 | Rats | Iscador M, 0.005–0.5 mg, im, qd | No difference | Metastases: no difference | [128] | |
Autochthonous
| ||||||
Methylnitrosurea-induced | Rats (Sprague Dawley) | Iscador M c. Arg., sc, 0,2 ml/day, 50 mg/week * 6 weeks | 75% | -16% | [124] |
Tumour, site | Animal | VAE | Tumour growth T/C (%) | Survival | Other outcomes | Reference |
---|---|---|---|---|---|---|
Human breast tumour
| ||||||
Breast | Mice | rML 0,3 ng/kg – 3 μg/kg, ip, qd * 5 * 2–4 w | No effect | [129] | ||
Murine breast tumour in mice
| ||||||
C3L5, adenocarcinoma; sc | Mice (C3H7HeJ) | ML I, 1 ng/kg, sc, q3d, day 7–19 | 160 | 27.6 lung-metastases | [130] | |
IL-2, twice 6 × 104 IU/mouse, ip q8h 2 * qd * 5 | 43 | 2.3 lung-metastases | ||||
Combination of ML 1 & IL-2 | 37 | 2.3 lung-metastases | ||||
Control | 7.5 lung-metastases | |||||
ECa, ip | Mice (ICR) | ML I, 80 ng, ip, day 1 | 70% died after 50 days | [131] | ||
A-chain of ML I, 100 μg, ip, day 1 | 80% died after 57 days | |||||
B-chain of ML I, 10 μg, ip, day 1 | 80% died after 58 days | |||||
Control | 100% died after 20 days | |||||
ECa, sc | Mice (BALB/c) | VAE 5 kDa peptides, 2 μg, it, day 7 | Severe necrosis, infiltration of lymphocytes and macrophages | [122] | ||
ECa, ip | Mice (CD-1) | Vester' Proteins, ip, 0.1 or 1 or 10 μ/kg, qd * 10 | ILS: 0, 33, and -33%I | [132] | ||
ECa | Mice | Polysaccharide („Viscumsäure“), ip, qd * 6 | Slight effect | [133] | ||
Adenocarcinoma EO 771 | Mice | Polysaccharide („Viscumsäure“), ip, qd * 6 | Moderate effect | [133] | ||
Murine breast tumour in rats
| ||||||
Walker Carcinosarcoma | Rats | Polysaccharide („Viscumsäure“), ip, qd * 6 | Moderate effect | [133] | ||
Other gynaecological tumour
| ||||||
Ovary, SoTü 3, ip | Mice (SCID) | rML 30 ng/kg, ip, qd * 5 * 12 | 35% mice alive at day 84 | 40% tumour-free mice at day 84 | [134] | |
rML 150 ng/kg, ip, qd * 5 * 12 | 10% mice alive at day 84 | 10% tumour-free mice at day 84 | ||||
rML 500 ng/kg, ip, qd * 5 * 12 | 75% mice alive at day 84 | 65% tumour-free mice at day 84 | ||||
Control | 15 mice alive at day 84 | 10% tumour-free mice at day 84 | ||||
Uterusepithelioma T-8 Guérin | Rats | Polysaccharide ("Viscumsäure"), ip, qd * 6 | Moderate effect | [133] |