Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer1 <FN ID="FN1"><NO>1</NO>All procedures were followed in accordance with the ethical standards of the Committee on Human Experimentation of the University of Erlangen and the Helsinki Declaration of 1975, as revised in 1983.</FN>

<F><UNL TYPE="BAR" STYLE="S">Purpose:</UNL></F> Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT). We used a time-dependent schedule to determine the maximal-tolerated dose and dose-limiting toxicities (DLTs; Grade 4 hematologic or Grade 3 other toxicity).<F><UNL TYPE="BAR" STYLE="S">Methods and Materials:</UNL></F> Patients with pancreatic cancer (n = 33), periampullary carcinoma (n = 1), or bile duct cancer (n = 2) were treated with 3-day conformal RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost. Concurrent cisplatin (20 mg/m2/d on Days 1–5 and 29–33) and gemcitabine (initially 600 mg/m2, weekly on Fridays 68 h before RT) were administered. Because of DLT, the doses were reduced to 500 mg/m2 weekly and then 500, 400, or 300 mg/m2 on Days 2, 5, 26, 33.<F><UNL TYPE="BAR" STYLE="S">Results:</UNL></F> DLT occurred at all dose levels of gemcitabine >300 mg/m2. Fourteen patients were treated at the recommended Phase II dose of gemcitabine (300 mg/m2) without DLT. The response to chemoradiation allowed 10 of 30 initially unresectable patients with primary pancreatic carcinoma to undergo radical surgery, including a complete response in 2 cases.<F><UNL TYPE="BAR" STYLE="S">Conclusions:</UNL></F> At the recommended Phase II dose, chemoradiation with gemcitabine and cisplatin can be administered safely in pancreatic carcinoma. However, at higher dose levels, toxicity is severe and frequent. Patients with a chance for conversion to resection could benefit from this schedule. [Copyright &y& Elsevier]