Clinical response benefit in patients with advanced pancreatic cancer - Role of gemcitabine

The prognosis for patients with pancreatic cancer remains extremely poor. A minority are surgically resectable, but the remainder suffer problems from locally invasive disease and also metastatic spread. Median survival in these patients approximates 4 months, with limited systemic options. Many chemotherapy drugs have been evaluated in pancreatic cancer End the results have been disappointing. Of the newer agents, gemcitabine shows the greatest promise in this tumour type. Gemcitabine is a novel pyrimidine antagonist with activity in a number of tumour types. Gemcitabine has been evaluated in 3 phase II studies revealing anti-tumour activity, albeit to a modest degree of around 10%. Many objective tumour reductions have been seen, and more importantly improved symptom control is reported by many investigators. In view of these findings a randomized phase III study was performed in the United States comparing gemcitabine with weekly 5-fluorouracil chemotherapy. Patients receiving gemcitabine achieved a higher response rate, improved symptom control and prolonged survival. These results were statistically significant. Despite the statistically significant improvement in objective response rate and survival in these patients, the outcome of systemic treatment in these patients remains extremely poor. These studies raise the question about the appropriate end-points for systemic chemotherapy trials in pancreatic cancer. Despite low objective response rates and survival improvement of approximately 6 weeks, these patients did achieve symptom control and improvements in quality of life (clinical benefit response). Gemcitabine is the first agent to be evaluated in this way and has been shown to be a benefit for approximately a quarter of the patients treated. Single agent gemcitabine could represent the standard on which to develop and evaluate new approaches. We need to improve on these results and one way forward is to look to gemcitabine containing combination chemotherapy regimens. The relative lack of toxicity associated with this drug lends itself to this approach.