Advances in the Genetic Screening, Work-up, and Treatment of Pancreatic Cancer.

Familiarity with the updated results in genetic screening and work-up presented here is essential to early diagnosis and possible cure. In the metastatic setting, we most frequently begin with the GTX regimen, consisting of Gemcitabine, Taxotere, and Xeloda. The regimen is based on our laboratory data demonstrating a synergistic increase in cell killing of pancreatic cancer cell lines. The combination takes advantage of the selective cell cycle effects of each of the three drugs. In our initial experience, we have seen a response rate of 40% at metastatic sites and 31% at the primary site after nine cycles of GTX. We are now conducting a formal phase II protocol to confirm these results. The median survival of this group of patients (at least 10.4 months) is as long as, or longer than other currently used regimens. In those patients who do not tolerate GTX or progress despite the regimen, we have found that a regimen of the same three drugs, administered on a different schedule, can produce responses. In the neoadjuvant (unresectable) setting, we treat with GTX initially and then follow with radiation; gemcitabine is used as a radiosensitizer during this treatment. An aggressive surgical approach with a team of surgeons were able to resect for cure 12 of the 16 patients who were initially unresectable; one year survival of these 12 was 100%; 2 year survival was 50%. Future work in this disease should focus on targeted agents such as bevacizumab.