Gemcitabine-based combination treatment of pancreatic cancer

Since the introduction of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), pancreatic cancer may no longer be regarded as a completely chemotherapy-resistant tumor. Good treatment tolerability and a low incidence of side effects are clear advantages of single-agent gemcitabine and enable its integration into combination regimens. Currently, the most widely used regimens involve combination partners such as 5-fluorouracil (5-FU), cisplatin, and docetaxel. Combinations of gemcitabine with cisplatin or 5-FU appear comparably active and tolerable. Comparative analysis of multiple phase II studies performed with gemcitabine/cisplatin showed response rates in the range of 11.4% to 58% and median survival times of 7.4 to 10 months, whereas various gemcitabine/5-FU-based regimens achieved response rates of 3.7% to 25% and median survival times of 4.4 to 10.3 months. In view of the great variety of schedules and inconclusive treatment results, an optimal regimen for the combination of 5-FU and gemcitabine still needs to be defined. Although the combination of gemcitabine with docetaxel has demonstrated activity, data showing a clear survival benefit are not yet available. It is also premature to evaluate the activity of combinations with irinotecan or oxaliplatin. Four-drug regimens indicate a possible improvement in treatment outcome. However, their application may be limited to selected patients with good performance status.