Gemcitabine and S-1 for Locally Advanced Unresectable or Metastatic Pancreatic Cancer

Inclusion criteria

• Adenocarcinoma of the pancreas that is already or will be histologically or cytologically proven.
• Patients must have either locally advanced (unresectable) or metastatic disease.
• Radiographically measurable disease is not required.
• No prior therapy for advanced pancreatic cancer. Treatment given in the adjuvant setting (radiation and/or chemotherapy, given either concurrently or systemically) does not count as prior therapy as long as progressive disease occurs > 6 months following completion of treatment.
• Greater than or equal to 18 years of age.
• ECOG performance status of 0 or 1 (See Appendix D).
• Laboratory criteria:
• ANC > 1500/µL
• Platelet count > 100,000/µL
• Hemoglobin > 9 g/dL (may be transfused or receive epoetin alfa to maintain or exceed this level)
• INR < 1.5 (except those subjects who are receiving full-dose warfarin
• Total bilirubin < 2.0 mg/dL
• AST or ALT < 5 times upper limit of normal for subjects with documented liver metastases; < 2.5 times the upper limit of normal for subjects without evidence of liver metastases
• Serum creatinine < 2.0 mg/dL
• Serum CA19-9 > 2X upper limits of normal.
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
• Women or men of reproductive potential must agree to use an effective contraceptive method during treatment and for 6 months afterwards.

Exclusion criteria

• Inability to comply with study and/or follow-up procedures
• Disease determined to be not amenable to biopsy upon review of radiographs by the oncologist and/or interventional radiologist.
• Clearly resectable disease in a patient who is an appropriate operative candidate.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
• Prior systemic therapy for advanced pancreatic cancer
• Pregnant (positive pregnancy test) or lactating
• Use of anti-neoplastic or anti-tumor agents not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study.
• Use of concurrent investigational agents is not permitted.

S-1 Specific Exclusion Criteria

• Is receiving a concomitant treatment with drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:
• Sorivudine, brivudine, uracil, dipyridamole, cimetidine, and folinic acid (may enhance S-1 activity).
• Allopurinol (may diminish S-1 activity).
• Phenytoin (S-1 may enhance phenytoin activity).
• Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).
• Pilocarpine (may inhibit cytochrome P-450 enzyme 2A6 activity).