The epothilone B analogue ixabepilone in patients with advanced hepatobiliary cancers: a trial of the University of Chicago Phase II Consortium.
OBJECTIVE
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.


METHODS
Eligible patients had previously-untreated, histologically-proven unresectable hepatobiliary cancer. Ixabepilone, 40 mg/m(2), was administered intravenously over 3 h every 21 days.


RESULTS
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%).


CONCLUSIONS
Single agent ixabepilone has limited activity in advanced hepatobiliary cancers.
Nimeiri
Halla S
HS
Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 North St. Clair Street, suite 850, Chicago, IL 60611, USA. h-nimeiri@northwestern.edu
Singh
Deepti A
DA
Kasza
Kristen
K
Taber
David A
DA
Ansari
Rafat H
RH
Vokes
Everett E
EE
Kindler
Hedy L
HL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D034261:Epothilones / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome; D014495:Universities; D055815:Young Adult
D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone; C093788:epothilone B