Phase II trial of gemcitabine plus capecitabine in patients with advanced biliary tract cancer

Abstract

4173 Background: Biliary tract cancer is a rare but aggressive cancer with median survival rarely exceeding 6 months. At present, there is no standard chemotherapy regimen for this disease. Recent trials suggest that new agents such as gemcitabine or capecitabine have activity in this disease. We conducted a phase II trial to evaluate the efficacy and toxicity of the gemcitabine plus capecitabine in patients with advanced biliary cancer. Methods: Patients with unresectable cholangiocarcinoma or gallbladder (GB) cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS ≤ 2 and measurable disease were enrolled. Treatment consisted of gemcitabine 1,000 mg/m2 IV day 1, 8, 15 with capecitabine 830 mg/m2 PO BID day 1 to 21, on a 4 week cycle. Results: Between Dec 2002 and Sep 2004, 34 pts were enrolled. Median age was 52 (32–64) with 20 males. Twenty (59%) had cholangiocarcinoma, 11 (32%) had GB cancer and 3 (9%) had ampulla of Vater cancer. Thirty pts were evaluable for response and toxicity. A total of 88 cycles were administered (median, 2; range, 1–9). One patient achieved CR and 3 pts achieved PR giving an overall response rate of 11.8% in intention-to-treat population (95% CI, 1.0–22.6%). And 10 pts (29.4%) had stable disease. Response rate for cholangiocarcinoma is 15.0% and GB cancer is 9.1%. The median time to progression of all patients was 2.6 months (mo) (95% CI, 1.3–3.9). The median overall survival was 7.8 mo (95% CI, 6.5–9.0). Grade 3/4 neutropenia and thrombocytopenia were noted in 40.0% and 16.7% of the pts, respectively. Grade 2/3 non-hematologic toxicities were asthenia (36.7% of pts), diarrhea (10.0%), stomatitis (10.0%) and hand-foot syndrome (3.3%). There was no treatment-related death. Gemcitabine on days 8 and 15 was skipped/reduced in 8%/13%, and 23%/30% of the patients, respectively. Therefore, the dose intensity of gemcitabine fell to 88.6% and 66.6% of the planned dose on days 8 and 15, respectively.Conclusions: The combination of gemcitabine and capecitabine in this four week cycle does not seem to have advantages in activity over other regimens in advanced biliary cancer. New dose schedule which can maintain the dose intensity of gemcitabine may improve the activity of this combination. No significant financial relationships to disclose.