title: Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival.
abstract: BACKGROUND
  The unfavourable side-effects of late-stage pancreatic cancer treatments call for non-toxic and effective therapeutic approaches. We compared the overall survival (OS) of patients receiving an extract of Viscum album [L.] (VaL) or no antineoplastic therapy.
  
  
  METHODS
  This is a prospective, parallel, open label, monocentre, group-sequential, randomised phase III study. Patients with locally advanced or metastatic cancer of the pancreas were stratified according to a binary prognosis index, composed of tumour stage, age and performance status; and were evenly randomised to subcutaneous injections of VaL extracts or no antineoplastic therapy (control). VaL was applied in a dose-escalating manner from 0.01 mg up to 10mg three times per week. Patients in both groups received best supportive care. The primary end-point was 12-month OS, assessed in a group-sequential analysis.
  
  
  RESULTS
  We present the first interim analysis, including data from 220 patients. Baseline characteristics were well balanced between the study arms. Median OS was 4.8 for VaL and 2.7 months for control patients (prognosis-adjusted hazard ratio, HR=0.49; p<0.0001). Within the 'good' prognosis subgroup, median OS was 6.6 versus 3.2 months (HR=0.43; p<0.0001), within the 'poor' prognosis subgroup, it was 3.4 versus 2.0 months respectively (HR=0.55; p=0.0031). No VaL-related adverse events were observed.
  
  
  CONCLUSIONS
  VaL therapy showed a significant and clinically relevant prolongation of OS. The study findings suggest VaL to be a non-toxic and effective second-line therapy that offers a prolongation of OS as well as less disease-related symptoms for patients with locally advanced or metastatic pancreatic cancer.
authors.affiliation: Clinical Research Dr. Tröger, Freiburg, Germany. Electronic address: troeger@crdt.de.
authors.forename: W
authors.initials: W
authors.lastname: Tröger
authors.forename: D
authors.initials: D
authors.lastname: Galun
authors.forename: M
authors.initials: M
authors.lastname: Reif
authors.forename: A
authors.initials: A
authors.lastname: Schumann
authors.forename: N
authors.initials: N
authors.lastname: Stanković
authors.forename: M
authors.initials: M
authors.lastname: Milićević
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001416:Back Pain / Q000139:chemically induced; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome; D028182:Viscum album / Q000737:chemistry*
chemical_list: D010936:Plant Extracts
keywords: Mistletoe; Pancreatic neoplasm; Randomised controlled trial; Survival analysis