A Study of Gemzar, Taxotere, and Xeloda for Adjuvant Pancreatic Cancer

The adjuvant treatment of resected pancreatic cancer is currently in flux. Many in the United States continue to use 5FU-based chemotherapy with radiation to the pancreatic bed. Some in the States, and most investigators in Europe, use a 5FU based chemotherapy-alone approach, based on the ESPAC-1 data. Many investigators believe that since gemcitabine is a more active drug in the metastatic setting, it should be moved "up front" in the adjuvant treatment of pancreatic cancer patients. At Columbia, we offer gemcitabine-based treatments with discussions with patients regarding risks, benefits, and limitations in current knowledge. We have usually offered radiation to those with positive margins, and chemotherapy alone to those without. Based on the early studies using gemcitabine, we believe that this will ultimately prove to be a more effective adjuvant drug than 5FU. Some patients have asked for GTX in the adjuvant setting as well, prompting the creation of this trial. Because of concerns about increased toxicity of this regimen, determination of patient safety will be the primary objective of this study, through careful monitoring of adverse events. This trial will be a chemotherapy-only study, offered to those with clean margins of resection. Taxotere administered "weekly" has activity in a variety of tumor types including breast, lung, ovarian and prostate cancer. Patients with advanced breast cancer, including some who had previously been treated with paclitaxel or anthracyclines, have responded to the weekly administration of Taxotere. The recommended dose of weekly Taxotere is 30-40 mg/m2/week for 6 out of 8 weeks. The same dose intensity can be achieved on a 3 out of 4 week basis. However, this protocol will give drugs 2 out of every 3 weeks, thus dose intensity is less. Weekly administration of Taxotere is well tolerated and produces substantially less myelosuppression than is observed with standard Taxotere administration every 3 weeks. Acute toxicities are uncommon, as is peripheral neuropathy. Prolonged treatment with weekly Taxotere, may result in chronic toxicities (including, asthenia (fatigue), anemia, edema, excessive lacrimation (epiphora), and onycholysis). Chronic toxicities are most prominent when Taxotere is administered on a continuous weekly basis, i.e., without a break, and are delayed in onset by providing breaks in treatment (for example, treating 6 out of 8 weeks or 3 out of 4 weeks); these chronic toxicities occur at a lower cumulative dose when a continuous weekly schedule of Taxotere is utilized. Premedication with dexamethasone is recommended for all patients receiving weekly Taxotere therapy to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. A variety of dexamethasone schedules have been used in studies with weekly Taxotere. Dexamethasone 4 to 8 mg x 3 doses taken orally the night before, the morning of, and the evening after Taxotere administration appears to be an effective schedule. We have found that a single low dose of 10 mg IV before the Taxotere usually prevents anaphylaxis and the pedal edema associated with this drug.