Randomized phase II comparison of dose-intense gemcitabine: Thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma

被引:379
|
作者
Tempero, M
Plunkett, W
van Haperen, VR
Hainsworth, J
Hochster, H
Lenzi, R
Abbruzzese, J
机构
[1] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA
[2] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
[3] Sarah Cannon Canc Ctr, Nashville, TN USA
[4] NYU, Med Ctr, New York, NY 10016 USA
关键词
D O I
10.1200/JCO.2003.09.140
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose : To conduct a randomized phase II trial of dose-intense 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. (C) 2003 by American Society of Clinical Oncology.
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页码:3402 / 3408
页数:7
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