Chemotherapy of pancreatic adenocarcinoma: initial report on two transplantable models in the Syrian hamster

Abstract

Experimental evaluation of chemotherapy of pancreatic cancer has been limited by the lack of suitable animal models, which have only recently become available. The present study is the first report on the chemosensitivity of two transplantable animal models of pancreatic adenocarcinoma. The single-agent antitumor activity of 5-fluorouracil, cyclophosphamide, mitomycin C (MMC), methotrexate, actinomycin D, vincristine, and two dose levels of Adriamycin (ADR) were tested against established palpable tumors of well-differentiated pancreatic ductal adenocarcinoma (WD PaCa), a solid tumor model of the Syrian hamster. None of the agents or dosages of ADR were effective against palpable WD PaCa tumors. ADR, MMC, streptozotocin, and the combination of 5-fluorouracil, ADR, and MMC were similarly ineffective when administered 1 week after WD PaCA implantation, while tumors were still nonpalpable. The behavior of poorly differentiated pancreatic ductal adenocarcinoma (PD PaCa), an ascitic model of the Syrian hamster, was studied for comparison. In vivo, with survival as the end point, PD PaCa is markedly sensitive to ADR, perhaps weakly sensitive to MMC, and resistant to streptozotocin. In vitro clonogenic assays from cultured PD PaCa and WD PaCa confirmed the pattern of response seen in vivo. The data suggest that these recently developed pancreatic cancer models can be profitably used and compared, both in vivo and in vitro, as examples of relatively chemotherapy resistant (WD PaCa) and more sensitive (PD PaCa) tumor models.