Viscum Album Extract May Increase Overall Survival in Adults with Locally Advanced or Metastatic Pancreatic Cancer Not Eligible for Antineoplastic Therapy

VISCUM ALBUM EXTRACT MAY INCREASE OVERALL SURVIVAL IN ADULTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC CANCER NOT ELIGIBLE FOR ANTINEOPLASTIC THERAPY Level 2 (mid-level) evidence Reference: Eur J Cancer 2013;49 (18):3788 At least 60% of medications used to treat cancer were originally derived from plants. Viscum album (European mistletoe) is widely used in Europe for the treatment of cancer, either alone or in combination with conventional antineoplastic agents. While its mechanism of action is unknown, parenterally administered extracts contain a variety of substances with cytotoxic, apoptotic, and immunostimulatory properties. Nevertheless, in a systematic review of 18 clinical trials (N 4 6800), researchers could find no convincing evidence for the benefits of V. album in cancer treatment. In the present study, Serbian researchers randomized 220 adults with locally advanced or metastatic pancreatic cancer to V. album extract (0.01 mg starting dose increased to 10 mg) self-administered subcutaneously three times weekly vs. no treatment. All patients were no longer eligible for antineoplastic therapy and received best supportive care at the same oncology center. No patient had brain metastases or life expectancy less than four weeks. Researchers had originally planned to recruit 428 patients but the trial was terminated early after a pre-specified interim analysis found increased overall survival with V. album. Comparing V. album to no treatment, median overall survival at the end of one year was 4.8 months vs. 2.7 months [hazard ratio 1⁄4 0.49 (95% CI 1⁄4 0.36–0.65)]. Findings remained consistent in subgroup analyses by age (r65 vs. 465), gender, disease stage (III vs. IV), and prognosis (good vs. poor). Adverse events were less common in the treatment group [14.5% vs. 48.2% (P o .05)]. In this open-label trial, parenteral V. album was associated with a significant increase in overall survival in patients with end-stage pancreatic cancer who were no longer candidates for conventional antineoplastic therapy. To put the average effect size into perspective, median survival time for 754 untreated patients was 3.9 months (range 1⁄4 3.1–7.0) in an analysis of 43 chemotherapeutic trials for advanced or metastatic pancreatic cancer. Although the open-label protocol increases the risk of performance bias, the influence of a placebo effect on survival in cancer is likely to be small. The fact that all patients received care at the same location minimizes the chance that patients received different levels of support, another potential source of bias.