SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma.

Gallbladder and cholangiocarcinomas represent a heterogeneous group of malignant diseases that commonly present at an advanced stage and have limited therapeutic options. Based on the role of the Ras-Raf-Mek-Erk pathway and the VEGF axis in biliary carcinomas, we conducted a phase II study of sorafenib in patients with advanced biliary cancers. Eligible patients had no prior therapy for metastatic or unresectable disease. Sorafenib was administered at 400 mg po twice daily continuously. The study was terminated after the first stage of accrual due to failure to meet the primary objective. A confirmed response rate of 0% (0%-11%) was observed. Thirty-nine percent of patients demonstrated stable disease (including 2 with unconfirmed PR). PFS was 3 months (95% CI: 2-4 months) and OS 9 months (95% CI: 4-12 months). The most common grade 3 and 4 toxicities included hand-foot skin reaction (13%), bilirubin elevation (13%), venous thromboembolism (10%), AST/ALT elevation (10%) and elevated alkaline phosphatase (10%). While treatment with sorafenib did not result in objective responses, patients with biliary cancers receiving this drug had some therapeutic benefit. Additional studies with sorafenib in combination with chemotherapy or other targeted agents may be warranted.