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).

Current status and future perspectives of clinical research in pancreatic cancer: Establishment of evidence by science

“…At present, the safety and efficacy of intraperitoneal chemotherapy with gemcitabine in resected PDA patients is under investigation. 91 Moreover, the pharmacokinetics of preoperatively administered intraperitoneal 5-FU in patients with resectable PDA was further studied. 92 With the development of innovative technology, 64 Cu-intraperitoneal radioimmunotherapy (ipRIT) with 64 Cu-labeled antiepidermal growth factor receptor antibody cetuximab as an adjuvant treatment after PDA surgery was investigated in a preclinical mouse model and showed effective results.…”

“…Meanwhile, Yamada et al 90 launched another phase I/II study and further confirmed the efficacy of intraperitoneal paclitaxel treatment. At present, the safety and efficacy of intraperitoneal chemotherapy with gemcitabine in resected PDA patients is under investigation 91 . Moreover, the pharmacokinetics of preoperatively administered intraperitoneal 5‐FU in patients with resectable PDA was further studied 92 .…”

ASO Author Reflections: First Do No Harm—Revisiting Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Trials to Reduce the Risk of Peritoneal Metastasis

“…In this regard, this present trial might even be regarded as an example for future treatment attempts. 6 FUNDING Open Access funding enabled and organized by Projekt DEAL. DISCLOSURE M.W.L.…”

“…Accordingly, this trial attests to the safety of HIPEC application after PDAC resection, which is reassuring. 6 …”

“…In this regard, this present trial might even be regarded as an example for future treatment attempts. 6 …”