Randomized P hase I I C omparison o f D ose-Intense Gemcitabine: T hirty-Minute I nfusion a nd F ixed D ose R ate Infusion i n P atients W ith P ancreatic A denocarcinoma

Purpose: To conduct a randomized phase II trial of doseintense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m 2 /min) in patients with pancreatic adenocarcinoma. Patients and Methods: In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m 2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. Results: Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P .013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P .094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P .014) and 2.2% (standard arm) versus 18.3% (FDR; P .007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P .046). Conclusion: Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine. J Clin Oncol 21:3402-3408. © 2003 by American Society of Clinical Oncology.