Molecular Mistletoe Therapy: Friend or Foe in Established Anti-Tumor Protocols? A Multicenter, Controlled, Retrospective Pharmaco-Epidemiological Study in Pancreas Cancer

Abstract

Mistletoe is often used as complementary therapy in oncology. The anti-tumor effects of mistletoe (Iscador) are well documented in-vitro in respect to inhibition of cell proliferation, induction of apoptosis, segmental activation of immune competent cells and trapping of chemotherapeutic drugs within cancer cells by modulating the inhibitory potential of P-glycoprotein (P-gp)-mediated transport of cell toxifying substances (cytotoxic drugs). However, the clinical activity of mistletoe treatment remains still controversial. Implementation of mistletoe therapy as supportive care into anti-cancer programs should be based on the best evidence and must continually be evaluated to ensure safety, efficacy, collection of new data, and cost-effectiveness. Useful domains that can be evaluated include symptom control, adherence to conventional treatment protocols, quality of life, individual outcome and potential advantages of a whole-system health approach. Here we report the results of a multicenter, controlled, retrospective and observational pharmaco-epidemiological study in patients suffering from a pancreatic carcinoma. After surgery the patients were treated by adjuvant chemotherapy with gemcitabine supported by Iscador, or with gemcitabine alone, or any other best of care, but not including Iscador. Using a novel methodological pharmaco-epidemiological design and statistical approach it could be shown that Iscador offers benefits--symptom control, overall survival--as supportive care within gemcitabine protocols of patients with surgically resected pancreatic carcinoma.

Sustained Partial Remission of Metastatic Pancreatic Cancer Following Systemic Chemotherapy with Gemcitabine and Oxaliplatin plus Adjunctive Treatment with Mistletoe Extract

“…Finally, the adjunctive treatment with mistletoe extracts might have contributed to the favorable outcome of this patient. In line with this, previous smaller-scale studies have suggested a potential benefit of such treatment in patients with various tumorentities,includingbreastcancerandgallbladdercancer [5,6].Thepotentialmechanismsbywhichmistletoeextracts may exert their antiproliferative activity have not yet been exploredindetail [7][8][9],butrecentstudieshavesuggestedan activationofdendriticcells,whichmayfacilitateantitumoral immune responses [10]. Whether mistletoe extracts exert …”

Intratumoral Mistletoe (Viscum album L) Therapy in Patients With Unresectable Pancreas Carcinoma

“…86 Recent studies have indicated a possible influence of mistletoe on survival in patients with colorectal or pancreatic carcinomas. 87,88 Matthes et al 87 demonstrated a lower adjusted hazard ratio of dying in patients with pancreatic carcinoma with subcutaneous mistletoe therapy combined with gemcitabine versus the control group who received gemcitabine alone. 80 A randomized controlled trial yielded prolonged survival from 2.7 to 4.8 months in patients with advanced pancreatic cancer not eligible for antineoplastic therapies who were treated with subcutaneous mistletoe in comparison to best supportive care.…”

NCCAM/NCI phase 1 study of mistletoe extract and Gemcitabine in patients with advanced solid tumors

“…Notably, in a large retrospective study of mistletoe therapy in nonmetastatic breast cancer patients, fewer adverse events and longer survival were observed in the mistletoe therapy group compared to conventional therapy alone [32]. In a comparable retrospective study design in pancreatic cancer patients, similar clinical outcomes were observed with fewer adverse events and improved survival in patients treated with mistletoe [33]. Despite compelling preclinical data and these isolated reports of clinical benefit of mistletoe preparations, recent reviews of clinical trials still note methodological weaknesses of current published studies on mistletoe [34] as well as conflicting results on tumor response and survival prolongation on treatment using various mistletoe preparations [35][36][37][38].…”