Knox JJ et al. (2005) Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 23: 2332

Biliary cancer has a poor prognosis. Surgical resection is a potential cure; however, only 25% of patients are resectable at presentation and relapse rates are high. The median survival time for unresectable biliary cancer is <1 year. There is currently no standard chemotherapy that can clearly prolong survival, but newer chemotherapies such as gemcitabine, newer fluorouracil regimens, capecitabine and platinum analogs seem to be active. Combinations of newer drugs may be more active still.

In this single-institute trial in 45 patients with locally advanced or metastatic biliary cancer, patients received a three-week cycle of oral capecitabine 650 mg/m2 twice-daily for 14 days with 30-minute intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of the cycle. 23 patients had cholangiocarcinoma and 22 had gallbladder cancer.

The overall response rate was 31% and disease stabilization was 42%, giving an overall disease-control rate of 73%. Median progression-free survival for disease-controlled patients was 10 months, and median overall survival was 14 months. Overall response rates for cholangiocarcinoma and gallbladder cancer were similar, but there was a shorter median survival in patients with gallbladder cancer, which probably reflects its more aggressive biology. The combination was generally tolerated well: no patients discontinued because of toxicity and there were no treatment-related deaths.

The authors conclude that the amount of antitumor activity seen and the tolerable toxicity profile may yield benefits for this population. A large, multicenter, randomized trial to determine whether this combination is superior to a single agent is warranted, and has the potential to change global practice.