A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers.

Purpose: Exatecan is a hexacyclic topoisomerase-1 inhibitor that has broad in vitro and in vivo activity. A multicenter phase II study to determine the antitumor activity of exatecan was conducted in patients with advanced cholangiocarcinoma and gallbladder carcinoma.

Methods: Patients with 0 to 1 prior chemotherapy regimens, adequate major organ function, and metastatic disease were eligible. Exatecan was administered at a dose of 0.5 mg/m2 IV over 30 minutes daily on days 1 through 5 every 21 days. The primary end point was overall response rate: complete response and partial response (PR). A Simon optimal 2-stage design was employed. Response was assessed every 6 weeks.

Results: Forty-two patients were enrolled. Two of 41 evaluated patients (4.9%) had a PR, 4 patients (9.8%) had a minor response, and 12 had stable disease. Twenty patients (51.2%) had progressive disease. The major toxicity was grade 3/4 neutropenia. The median overall survival was 7 months. The 6-month survival rate was 56.1% and the 12-month survival rate was 31.7%.

Conclusion: Exatecan has minimal activity in advanced biliary tree cancers. Toxicity was predictable and manageable.