Gemcitabine improves safety for adjuvant pancreatic cancer therapy

Medical Tribune July 2009 P8
David Brill

Gemcitabine is a safer option than 5-fluorouracil/folinic acid (5-FU/FA) for the adjuvant treatment of pancreatic cancer, results of a phase III trial suggest.

Investigators from the European Study Group for Pancreatic Cancer (ESPAC) found that there was no difference in survival between the two therapies, but fewer side effects with gemcitabine.

The study included 1,088 patients who were randomized to one of the two therapies following resection of pancreatic ductal adenocarcinoma. It is the largest adjuvant trial ever carried out in this patient population and the first to directly compare gemcitabine against 5-FU/FA in the adjuvant setting, the researchers say.

“This study is important because it shows no difference between these treatments in prolonging survival,” said lead author Professor John Neoptolemos, head of surgery and oncology at the University of Liverpool, UK.

“On the basis of the safety profile, however, this trial shows that gemcitabine is likely to be the preferred adjuvant therapy. We are now also looking at combining the two treatments to see if we get a better response, because the drugs have different mechanisms of action,” he said.

After a median of 34 months follow up, overall survival times were 23.6 months for patients receiving gemcitabine and 23 months for those receiving 5-FU/FA.

Ten percent of 5-FU/FA patients experienced treatment-related hospitalization, compared to 3.5 percent of gemcitabine patients. Other adverse events which were more common in the 5-FU/FA group included stomatitis (10 percent versus 0 percent; P<0.001) and diarrhea (13 percent versus 2 percent; P<0.001). Some gemcitabine patients, conversely, experienced a drop in platelet count which was not seen in the 5-FU/FA group (1.5 percent versus 0 percent; P=0.0034).

Gemcitabine is typically used in the US for the adjuvant treatment of pancreatic cancer, whereas 5-FU/FA is the standard in some parts of Europe. It was previously unclear which treatment offered a better prognosis.

The trial, known as ESPAC-3, included patients from 16 countries, who were randomized between 11 July 2000 and 12 Jan 2007. Ages ranged from 31 to 85, with a median of 63.

The results will also help to reinforce the design of the upcoming ESPAC-4 trial, added Neoptolemos. The study is set to compare gemcitabine alone against gemcitabine plus capecitabine – a prodrug which is converted to 5-FU in tumors.