epothilone-a and Biliary-Tract-Neoplasms

Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver.. Eligible patients had previously-untreated, histologically-proven unresectable hepatobiliary cancer. Ixabepilone, 40 mg/m(2), was administered intravenously over 3 h every 21 days.. Between January 2002 and April 2005, 54 patients (19 hepatocelluar carcinoma, 13 cholangiocarcinomas, 22 gallbladder carcinomas) were enrolled; 47 patients were evaluable for efficacy. The objective response rate was 8.5%; 51% had stable disease. Median overall survival was 7.0 months (95% CI, 5.0 to 10.8 months) and median progression-free survival was 2.6 months (95% CI, 1.4 to 4.1 months). Grade 3/4 toxicities included neutropenia (39%), fatigue (9%), allergic/hypersensitivity reaction (4%) and sensory neuropathy (4%).. Single agent ixabepilone has limited activity in advanced hepatobiliary cancers.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biliary Tract Neoplasms; Epothilones; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Treatment Outcome; Universities; Young Adult