Efficacy of First- & Second-Line Treatment in an In Vivo Model of Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas

Abstract

Introduction: Poorly differentiated neuroendocrine carcinoma of the pancreas (PD-NEC) is a rare but deadly pancreatic tumor type with limited systemic treatment options. The absence of a preclinical animal model of PD-NEC has made translational research for this rare tumor type difficult. The aim of this study was to develop a novel patient-derived xenograft (PDX) of PD-NEC and assess the efficacy of currently proposed first- and second-line therapeutics in this fatal subtype of pancreatic cancer. Methods: With appropriate consent and approval, patient tissue was obtained from surgical resection and implanted into the flanks of NOD/SCID mice. Mouse tumors were verified as PD-NEC by a Mayo Clinic pathologist. Mice were randomized into 4 groups and treated for 3 weeks: 1) vehicle, 2) cisplatin + irinotecan, 3) capecitabine + temozolomide, and 4) everolimus. Treatment efficacy was measured by change in tumor volume as compared to vehicle. Toxicity was assessed by change in mouse weight during treatment. Results: Figure 1 demonstrates tumor volume fold change over time for each treatment arm. Capecitabine + temozolomide arm demonstrated a 47% decrease in tumor volume fold change versus vehicle (p=0.0001) while cisplatin + irinotecan arrested tumor growth with an average fold change of 1.02 versus vehicle (p=0.019). Figure 2 demonstrates the change in mouse weight throughout the course of the treatment study. Conclusions: PD-NEC is a rare but lethal pancreas cancer. To our knowledge, this is the first report of treatment efficacy of both first-line and second-line combinatorial therapeutics in a validated animal model of PD-NEC.