The CHARM Trial (CHemotherapy for Ablation and Resolution of Mucinous Pancreatic Cysts): The Initial Pilot Study for the Prospective, Randomized, Double-Blind, Single-Center Clinical Trial

Abstract

Introduction: Mucinous pancreatic cystic lesions carry significant potential for progression into pancreatic cancer. Currently radiographic surveillance or surgical resection is generally recommended for these cysts, both of which have significant limitations. Recently, EUS-guided cyst ablation has emerged as promising alternative treatment approach. Previous studies have shown that EUS-guided ethanol lavage of pancreatic cysts is safe and results in complete cyst resolution in roughly one-third of patients without recurrence at a follow-up of 26 months. Subsequent studies demonstrated marked increases in rates of ablation (62-78%) with infusion of paclitaxel following ethanol lavage, which raises the question of whether alcohol is necessary for effective ablation. Importantly, ethanol extravasation is felt to cause the 2 most common complications in previous trials, abdominal pain (12-16%) and pancreatitis (3-5%), and is felt to be the highest risk element of the technique. This study hypothesizes that the removal of alcohol lavage prior to chemotherapy infusion will not impair ablation rates and will decrease complication rates. A secondary aim of this study is to assess whether a custom chemoablation cocktail tailored to pancreatic neoplasia (paclitaxel+gemcitabine) will improve ablation rates overall. Methods: Patients with mucinous or indeterminate type pancreatic cysts of 1-5 cm without signs of malignancy were randomized to undergo either EUS-guided lavage with 80% alcohol or normal saline, followed by infusion of 3 mg/mL paclitaxel + 19 mg/mL gemcitabine (both arms). Patients were evaluated postop, at 72 hours, and by CT scan at 3, 6, and 12 months to assess response and complication rates. Results: The initial 13 patients of this trial (expected to have an N of 78 when complete) were randomized for this pilot study with 11 patients then able to be treated. The overall reduction in cyst surface area was 70% at 3 months and 83% at 6 months. At 3 months, size reduction was 62.5% in the alcohol infusion arm and 74% in the alcohol-free arm. Complications were mild pancreatitis (1/5) in the alcohol arm. Conclusion: The treatment of mucinous pancreatic cysts with either alcohol or saline lavage followed by gemcitabine-paclitaxel infusion is feasible and safe in this limited pilot study. Initial results indicate that alcohol-free ablation does not impair ablation efficacy. Disclosure - Dr. Moyer is a consultant for Boston Scientific Corp. This is unrelated to the current research.