Pharmacokinetics of natural mistletoe lectins after subcutaneous injection

Huber, Roman; Eisenbraun, Jürgen; Miletzki, Barbara; Adler, Michael; Scheer, Rainer; Klein, Reinhild; Gleiter, Christoph H.

doi:10.1007/s00228-010-0830-5

Cited by 26 publications

(25 citation statements)

References 14 publications

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“…administration have shown that molecules applied i.v. were eliminated up to three times faster than when applied s.c [45–47]. This finding might also help to explain the much higher frequency of pyrexia observed in s.c. patients compared to i.v.…”

Section: Discussionmentioning

confidence: 82%

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study

Steele

Axtner

Happe

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this “off-label” application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs) to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6%) reported 32 ADRs of mild (59.4%) or moderate severity (40.6%). No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%), versus prior to chemotherapy (1.6%). ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

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Section: Discussionmentioning

confidence: 82%

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study

Steele

Axtner

Happe

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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“…Unfortunately, there is literature lacking showing the pharmacokinetics of mistletoe extracts in mice or humans, but Huber et al . showed for subcutaneous injections in humans, that serum mistletoe lectin levels are highly variable after injection [61]. Furthermore, Frantz et al .…”

Section: Discussionmentioning

confidence: 99%

Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma

Twardziok

Kleinsimon

Rolff³

et al. 2016

PLoS ONE

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Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with viscum, TT and viscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while viscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that viscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.

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“…Interestingly, except the lower frequency of diarrhea, no specific improvement during mistletoe treatment occurred (Table 2). Possible mechanisms how mistletoe treatment could improve the global health status include immunological effects and elevating body temperature [27], because immunological disturbances and an altered circadian rhythm are factors that may contribute to reduced QoL in cancer patients [28]. …”

Section: Discussionmentioning

confidence: 99%

Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study

Kim

Yook

Eisenbraun

et al. 2012

BMC Complement Altern Med

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BackgroundMistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM® Quercus, aVQ) in patients with gastric cancer.Patients and Methods32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16+/CD56+ and CD 19+ lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later.ResultsGlobal health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16+/CD56+ and CD 19+ lymphocytes and liver function tests measured by ANOVA.ConclusionAdditional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075.

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Pharmacokinetics of natural mistletoe lectins after subcutaneous injection

Abstract: International audienc

Cited by 26 publications

References 14 publications

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study

Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma

Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study

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