Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy

Abstract

Background: Advanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients.

Materials and methods: This study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared.

Results: The median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05).

Conclusion: GEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment.

Trial registration number: NCT02635971.

Date of registration: 21/12/2015.

Keywords: GEMOX; Intravenous chemotherapy; Pancreatic arterial infusion; Pancreatic head and neck tumors; Unresectable pancreatic cancer.

Fig. 1

Patient inclusion chart and treatment plan

Fig. 2

Representative images of DSA and CT in PAI-treated patients with different tumor-sites. (A) Anatomical diagram of blood supply of pancreatic tumors. (B-C) Pancreatic head and neck tumors, chemotherapy drugs were infused through the gastroduodenal artery or superior mesenteric artery; (D-E) Pancreatic body and tail tumors, chemotherapy drugs were infused through the splenic artery or superior mesenteric artery. Yellow arrows indicate tumor lesions

Fig. 3

Summary of the primary and secondary endpoints. Kaplan-Meier analysis of (A) Overall survival, (B) Progression-free survival, (C) 1-year survival, and (D) 6-month survival in the ITT population. Objective response rate (E) and disease control rate (F) in PAI and IVC group, respectively

Fig. 4

Kaplan-Meier survival curves of tumor-site subgroups. (A) Overall survival and (B) Progression-free survival comparison between tumor-site subgroups of pancreatic head and neck tumor lesions and pancreatic body and tail lesions in the whole cohort. Overall survival of pancreatic head and neck tumors and body and tail tumors in PAI group (C) and IVC group (D)

Fig. 5

Changes of blood indexes before and after treatment. (A) Serum tumor markers and blood biochemistry; (B) Blood routine and biochemistry. Ca19-9 carbohydrate antigen199, Ca242 carbohydrate antigen242, TBIL total bilirubin, ALP alkaline phosphatase, ALT amino alanine transferase, AST aspartate amino transferase, LDH lactate dehydrogenase, CRE creatinine, TP total protein, WBC white blood cell, GRAN neutrophils, RBC red blood cell, HGB hemoglobin, PLT platelet