A phase 2 trial of gemcitabine, 5-fluorouracil, and radiation therapy in locally advanced nonmetastatic pancreatic adenocarcinoma

BACKGROUND: The purpose of this study was to assess the efficacy and safety of 5-fluorouracil (5FU) and gemcitabine administered concurrently with radiation in patients with locally advanced, nonmetastatic pancreatic cancer. METHODS: Eligible patients had histologically confirmed pancreatic adenocarcinoma deemed locally unresectable without evidence of metastatic disease. In addition, all patients underwent laparoscopy or laparotomy before study entry to rule out peritoneal carcinomatosis. Patients received radiation therapy (50.4 Gy) with concurrent infusional 5FU (200 mg/m² 5 days/week) and weekly gemcitabine (200 mg/m²). After a 3-week break, patients received weekly gemcitabine at 1000 mg/m² for 3 of 4 weeks, for 4 cycles. The primary endpoint of the trial was the proportion of patients surviving 9 months from study entry. Secondary endpoints included objective tumor response, CA19-9 response, overall survival (OS) time to progression (TTP), and toxicity. RESULTS: Between November 2001 and October 2004, 81 patients were enrolled, 78 of whom were eligible for analysis. With a median follow-up of 55.2 months, the median OS was 12.2 months (95% confidence interval [CI], 10.9-14.9) and the median TTP was 10 months (95% CI, 6.4-12.0). An objective tumor response was seen in 19 patients (25%), and among 56 patients with an elevated CA19-9 at baseline, 29 (52%) had a sustained CA19-9 response. Overall, 41% of patients had grade 3 or greater treatment-related gastrointestinal adverse events. CONCLUSIONS: The combination of 5FU, gemcitabine, and radiation is well tolerated. Survival is comparable with the best results of other recent studies of 5FU and radiation or gemcitabine and radiation.