Newer approaches to gemcitabine-based therapy of pancreatic cancer: Fixed-dose-rate infusion and novel agents

Purpose: To review the use of gemcitabine-based therapy in pancreatic cancer, including fixed-dose-rate (FDR) infusion and novel combinations. Results: On the basis of pharmacokinetic data, studies have been performed using an FDR of gemcitabine of 10 mg-m(2)/min in an effort to maintain a critical plasma concentration of gemcitabine, and thus increase tumor cytotoxicity and therapeutic efficacy. The dose-limiting toxicities in Phase I studies were mucositis and myelosuppression. A multicenter Phase II study compared two schedules of gemcitabine in patients with pancreatic cancer, a single dose of 2200 mg/m(2) infused for 30 min, and a constant infusion of 1500 mg/m(2) given at 10 mg/m(2)/min. A somewhat improved response rate and survival for the FDR arm compared with the 30-min-infusion arm was observed. In addition, a wide variety of new compounds targeting specific molecules involved in cell control, cell growth, and apoptosis have been used in combination with gemcitabine and are reviewed. Conclusion: Further development of FDR gemcitabine in combination with other chemotherapeutic agents is ongoing. Because none of the new compounds investigated has as yet shown improvement compared with single-agent gemcitabine in prospectively randomized trials, gemcitabine remains the standard of care in pancreatic cancer. (C) 2003 Elsevier Inc.