Fixed Dose Rate Gemcitabine Infusion May Be Best for Pancreatic Cancer

Laurie Barclay, MD

September 17, 2003

Sept. 17, 2003 -- Fixed dose rate (FDR) infusion of gemcitabine improved survival of patients with pancreatic cancer compared with the standard dose-intense protocol, according to the results of a randomized phase II trial published in the Sept. 15 issue of the Journal of Clinical Oncology.

"The purpose of this trial was to assess the efficacy of two dose-intense schedules of gemcitabine using a standard infusion time and an infusion rate based on pharmacokinetic principles (FDR), to select a dose and infusion rate for further development in combination with potentially synergistic drugs," write Margaret Tempero, MD, from the University of California, San Francisco, Comprehensive Cancer Center, and colleagues.

In this prospective study, 92 patients with locally advanced and metastatic pancreatic adenocarcinoma were randomized to the standard treatment group (2,200 mg/m 2 gemcitabine over 30 minutes) or the FDR group (1,500 mg/m 2 gemcitabine over 150 minutes) on days 1, 8, and 15 of every four-week cycle. At study entry, 91% of the patients had metastatic disease.

Although the primary end point of time to treatment failure was similar in both treatment groups, median survival for all patients was 5.0 months in the standard group and 8.0 months in the FDR group ( P = .013). For patients with metastases, median survival was 4.9 months in the standard group and 7.3 months in the FDR group ( P = .094).

Patients in the FDR group also fared better in terms of one-year survival (28.8% vs. 9%; P = .014) and two-year survival (18.3% vs. 2.2%; P = .007). Pharmacokinetic analyses showed a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR group ( P = .046). Time to progression and objective response were similar in both groups.

Hematologic toxicity was more common in the FDR infusion group, but the number of dose modifications and the number of dose omissions were comparable in both groups.

"This study does not definitively favor one regimen over the other," the authors write. "However, both the pharmacologic and clinical data support the continued evaluation of the FDR infusion strategy for gemcitabine, either alone or in combination with other agents."

Eli Lilly, the maker of gemcitabine, supported this study. The authors report no potential conflicts of interest.

J Clin Oncol. 2003;21(18):3402-3408

Reviewed by Gary D. Vogin, MD

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