Abstracts
2002 Digestive Disease Week

# 108216 Abstract ID: 108216 Combination Chemotherapy Improves Survival in Pancreatic Cancer.
Peter Buchler, Oscar J Hines, Manuela Buchler, Guido Eibl, Moritz N Wente, Helmut Friess, William H Isacoff, Howard A Reber, Heidelberg, Germany; Los Angeles, CA

Background: Pancreatic cancer (PaCa) is resistant to current chemoradiation protocols. As many as 70% of PaCa adenocarcinoma express the HER2/neu oncogene. We have previously demonstrated that treatment with HerceptinTM (Herc) slowed progression of tumors in a human PaCa/nude mouse chimera model. Aim: The aim of this study was to analyze the therapeutic efficiency of combination therapy including Herc, gemcitabine (gem), and taxotere (tax) as a new therapeutic approach to pancreatic cancer. Methods: In vitro expression of HER2/neu was characterized in the PaCa cell lines AsPc-1 (A1), Capan-1 (C1), HPAF-II (HP2), MIA PaCa-2 (MP2) and PANC-1 (P1). Tumor cell growth was analyzed with MTT assays using various doses and combinations of Herc, gem and tax. Tumor growth in vivo was studied using an orthotopic murine model for pancreatic cancer with MP2 and HP2 xenograft tumors (each n=10). Treatment (Herc, gem, gem+tax, gem+Herc+tax) was initiated after 7 weeks of extensive tumor growth and continued until sacrifice or death. Results: All pancreatic cancer cell lines expressed HER2/neu with the highest levels found in MP2 cells and lowest in HP2 cells. In vitro treatment of PaCa cells with Herc alone inhibited growth mainly of cell lines with high levels of HER2/neu. Treatment with gem or with gem+tax or gem+tax+Herc enhanced the cytostatic efficiency in comparison to monotherapy of each substance (p<0.05). In vivo a dramatic increase in survival time was seen in MP2 and HP2 xenograft tumors treated with various combinations of gem, tax and Herc. The rate of metastases was significantly lower in animals treated with gem+tax+Herc in comparison with control or Herc treated animals (p<0.05). However, survival was not enhanced when Herc was added to gem+tax (table). Conclusion: Although Herceptin monotherapy appears to be of benefit over no therapy, the addition of Herceptin to gemcitabine and taxotere does not appear to offer any advantage. Survival of animals treated with gemcitabine and taxotere combination therapy was better than monotherapy alone.