Table II.
Methodological characteristics of studies (n=37), considering animal species, tumor cell origin, quality criteria (blindness, randomization, sample size) and incidence of toxic effects.
| Author/year | Animal species | Tumor type | Blinded study | Control | Random allocation | Number of animals/group | Toxicity | (Refs.) |
|---|---|---|---|---|---|---|---|---|
| Han et al, 2015 | Mice | Melanoma | NR | Negative: 0.85% saline Positive: VAE + PKA | Yes | Toxicity test: 5; Antitumor effect: 9 | Toxicity test: No deaths or clinical morbidity, no significant effect on body weight. No significant change in food intake. | (53) |
| Delebinski et al, 2015 | Mice | Mesenchymal (Leukemia) | NR | Negative: CD; Positive: ARA-C | NR | 10 | Very good tolerability; no evidence of toxicity measured by body weight and autopsy with liver, spleen histology; some spleen atrophy in group ARA-C. | (25) |
| Facina et al, 2014 | Mice | Melanoma | NR | Negative: Distilled water | NR | 6 | NR | (44) |
| Stan et al, 2013 | Mice | Epithelial | NR | Negative: Vehicle Tumor control (EAC) Positive control: DOXO | NR | 8 | NR | (58) |
| Strüh et al, 2013 | Mice | Melanoma | NR | Negative: CD vehicle | NR | 8–9 (additional 4 animals/group for histology) | Higher dose: STT caused skin necrosis, apathy and weight loss, with 3 dropouts. All treatments caused local skin inflammation and inflammatory peritumoral infiltrates. Lower dose: No toxic effects; reduced inflammatory infiltrates. | (26) |
| Podlech et al, 2012 | Mice | Mesenchymal (Glioma and astrocytoma) | NR | No treatment; vehicle | NR | 6 | NR | (52) |
| Li et al, 2011 | Mice | Epithelial | NR | Negative control: PBS | NR | 10 | NR | (69) |
| Thies et al, 2008 | Mice | Melanoma | NR | Negative control: PBS | NR | 20 | Vitality score, behavior, physiological response and water and food intake assessed: No animals exhibited changes; no treatment. related lesions were found on biopsy. | (33) |
| Seifert et al, 2008 | Mice | Mesenchymal (Leukemia) | NR | Negative control: PBS Positive control: CPA | NR | 8 (treated groups) 10 (control groups) | Tolerability was very good; no changes in body weight or assessed hematological parameters. VA-P was more toxic than VA-A in vitro, especially at the higher concentrations (50 mg/kg). | (59) |
| Cebovic et al, 2008 | Mice | Epithelial | NR | Placebo; tumor control | NR | 6 | NR | (27) |
| Beuth et al, 2006 | Mice | Epithelial | NR | Negative control: PBS | NR | 8 | All animals free from side effects (behavior, appearance). | (68) |
| Duong Van Huyen et al, 2006 | Mice | Melanoma | NR | Untreated; vehicle | NR | 6 | NR | (67) |
| Pryme et al, 2004 | Mice | Mesenchymal (lymphoma) | NR | Standard diet | NR | 5 | NR | (70) |
| Yoon et al, 2003 | Mice | Epithelial and mesenchymal | NR | Negative control: PBS | NR | 5 | NR | (66) |
| Braun et al, 2002 | Mice | Mesenchymal (Lymphoma and sarcoma) | NR | PBS | NR | 10 | NR | (49) |
| Elsässer-Beile et al, 2001 | Rats | Epithelial | NR | Tumor control | NR | Control: 56 Treated: a) 14; b) 23; c) 22; d) 19; + 15 in group b) for cytokine mRNA assessment | NMU-induced carcinoma was accompanied by high mortality associated with the tumor or procedure (15/71 in the control group and 40/123 in the treated groups). All treated animals exhibited weight loss over the 6 weeks of treatment. | (22) |
| Braun et al, 2001 | Mice | Mesenchymal (Lymphoma and sarcoma) | NR | PBS | NR | 8 | NR | (48) |
| Schaffrath et al, 2001 | Mice | Mesenchymal (Lymphoma and sarcoma) | NR | PBS | NR | 10 | No toxic effects (agility, food intake, body weight). | (23) |
| Burger et al, 2001 | Mice | Epithelial and melanoma | NR | Negative control: PBS; positive control: DOXO, 5-FU | NR | 5–7 | VA less toxic than DOXO (body weight; mortality); not different from 5-FU. | (45) |
| Timoshenko et al, 2001 | Mice | Epithelial | NR | Healthy mice; tumor control | NR | 10 (2 rounds), 8 (1 round) | Nephrotoxicity. | (47) |
| Park et al, 2001 | Mice | Melanoma | NR | PBS; no treatment | NR | NR | NR | (46) |
| Zarcovic et al, 2001 | Mice | Epithelial | NR | Saline | NR | 7 | NR | (65) |
| Mengs et al, 2000 | Mice | Epithelial | NR | Cehicle | Yes | 13 | NR | (54) |
| Schumacher et al, 2000 | Mice | Epithelial | NR | PBS + Tween-80 | NR | 20 | NR | (24) |
| Kunze et al, 2000 | Rats | Epithelial | NR | No treatment | Yes | 60/70 in tumor-bearing groups; 20 in untreated and non-tumor bearing groups | NR | (40) |
| Antony et al, 1999 | Mice | Melanoma | NR | No treatment | NR | 14 | NR | (64) |
| Lenartz et al, 1998 | Rats | Mesenchymal (glioma) | NR | PBS | NR | 5 | NR | (50) |
| Yoon et al, 1998 | Mice | Epithelial, melanoma, mesenchymal | NR | PBS | NR | 5 | NR | (51) |
| Weber et al, 1998 | Mice | Melanoma | NR | PBS + povidone | Yes | 5 | No toxic effects (mortality; clinical signs; food intake; body weight; no significant findings on necropsy). | (55) |
| Zarcovic et al, 1998 | Mice | Melanoma | NR | Culture medium | NR | 5 | NR | (21) |
| Kunze et al, 1998 | Rats | Epithelial | NR | No treatment | NR | 75 | NR | (41) |
| Zarkovic et al, 1997 | Mice | Melanoma | NR | Saline | NR | 14 (total number, allocation NR) | NR | (63) |
| Jurin et al, 1997 | Mice | Mesenchymal | NR | Healthy mice; saline | NR | 8–12 | NR | (62) |
| Antony et al, 1997 | Mice | Melanoma | NR | No treatment | NR | 8 | NR | (61) |
| Kunze et al, 1997 | Rats | Epithelial | NR | No treatment | NR | Controls: 57; Treated: 61 | 43/100 controls and 59/120 treated mice died by causes associated with the tumor-induction procedure. | (42) |
| Kuttan et al, 1997 | Mice | Mesenchymal, melanoma | NR | No treatment | NR | 15 (carcinogenesis) 8–10 metastasis | NR | (60) |
| Kuttan et al, 1996 | Mice | Mesenchymal | NR | Saline | Yes | 15 | No toxic effects (body weight, food intake); all animals survived and were healthy at the end of the experiment. | (56) |
NR, not reported; VAE, Viscum album extract; PKA, polysaccharide K; CD, cyclodextrins; ARA-C, cytarabine; EAC, Ehrlich ascites carcinoma; DOXO, doxorubicin; STT, solubilized triterpenes; CPA, cyclophosphamide; VA-P, mistletoe grown on pine; VA-A, mistletoe grown on fir; NMU; N-methyl-N-nitrosourea 5-FU, 5-fluorouracil.