Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

OBJECTIVES: Primary * Determine the maximum tolerated dose of pemetrexed disodium when given in combination with upper abdominal radiotherapy after induction therapy comprising gemcitabine hydrochloride and pemetrexed disodium followed by consolidation therapy with gemcitabine hydrochloride in patients with locally advanced pancreatic cancer. * Determine the quantitative toxicity of this regimen in these patients. Secondary * Determine the quantitative and qualitative dose-limiting toxicities of pemetrexed disodium in combination with upper abdominal radiation therapy. * Evaluate patterns of failure, response, and survival of these patients at 1 year OUTLINE: This is an open-label, nonrandomized, dose-escalation study of pemetrexed disodium. * Induction therapy: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for 3 courses. Approximately 2 weeks later, patients without disease progression proceed to chemoradiotherapy. * Chemoradiotherapy: Patients receive pemetrexed disodium IV over 10 minutes on days 1, 15, and 29 and undergo radiotherapy once daily 5 days a week for 5 ½ weeks. Approximately 2-3 weeks later, patients without disease progression proceed to consolidation therapy. Cohorts of 3-9 patients receive escalating doses of pemetrexed disodium during chemoradiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≤ 20% or ≤ 2 of 9 patients experience dose-limiting toxicity. * Consolidation therapy: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.