Superiority of extended neoadjuvant chemotherapy with gemcitabine in pancreatic cancer: A comparative analysis in a clinically adapted orthotopic xenotransplantation model in SCID beige mice

Abstract

Background: Intensive efforts are being made to develop new approaches for adjuvant or neoadjuvant treatment in pancreas carcinoma. Recently, we established an animal model simulating an adjuvant therapeutic treatment setting. In order to additionally mimic a neoadjuvant treatment regime, we further developed the preclinical testing system. Methods: Subtotal pancreatectomy was performed in mice after orthotopic inoculation of human pancreatic cancer cells (PancTu1). Four different settings were investigated: control without chemotherapy, adjuvant, neoadjuvant and extended neoadjuvant treatment protocols employing gemcitabine. All animals were autopsied 28 days after tumor resection. Results: 28 of 32 animals survived the treatment setting. The largest pancreatic tumor masses were seen in animals without any chemotherapy, and the different chemotherapy protocols resulted in a stepwise reduction of the tumor mass. The mean weight of locally recurrent tumors was 553.1 ± 133.2 mg (control) and 44 ± 21.8 mg (adjuvant treatment group). Animals in the neoadjuvant treatment group developed larger tumor masses (215 ± 191.3 mg) but fewer organ metastases. An extended neoadjuvant treatment setting proved to be most effective, resulting in the smallest tumor masses (25.6 ± 8.8 mg) and the fewest organ metastases. Conclusion: Murine orthotopic tumor resection is an excellent simulation of the clinical situation and therefore provides a relevant option for preclinical comparative testing of new therapeutic strategies. To our knowledge, this is the first model described, in which all different therapeutic regimes for pancreatic carcinoma were systematically compared with each other in a standardized manner. The extended neoadjuvant regime proved to be superior. ©2007 Landes Bioscience.