Phase I-II trial of twice-weekly gemcitabine and concomitant irradiation in patients undergoing pancreaticoduodenectomy with extended lymphadenectomy for locally advanced pancreatic cancer

Define the maximum tolerated dose (MTD), tolerability, and efficacy of gemcitabine given concomitantly with radiotherapy in patients with locally advanced pancreatic cancer. Patients were required to have locally advanced T1–T3 resectable pancreatic cancer. Gemcitabine, given twice weekly before irradiation as a 30-min infusion, was tested at 3 dose levels: 20, 50, and 100 mg/m 2. The radiation dose was 50.4 Gy (ICRU) in 28 fractions. The targeted irradiation volume included the tumor, edema, and a 1-cm margin. Twenty-eight of 34 patients was eligible for analysis of the treatment. The median age was 67 years (range 38–82). Six patients had T1, 9 had T2, and 19 had T3 diseases (AJCC). Dose-limiting toxicities were Grade 4, fatigue and nausea; Grade 3, thrombocytopenia, diarrhea, and infection. The MTD established was at the 50-mg/m 2 gemcitabine dose. A total of 21 of 28 patients underwent surgery: 18 had pancreaticoduodenectomy, 2 had total pancreatectomy, and 1 for palliative surgery. At the time of analysis, 13 of 28 (46%) were disease-free. The estimated median survival was 25 months and overall survival rate at 2 years (Kaplan-Meier) was 55%. Gemcitabine 50 mg/m 2 given twice weekly with concomitant irradiation induces acceptable and manageable toxicity and might prolong survival.