A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery. Methods: This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m2 body surface area heated to 42 °C for 1 hour. Results: Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk. Conclusion: Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified. Registration Number: NCT02863471 (http://www.clinicaltrials.gov).