Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial.
BACKGROUND
Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma.


METHODS
We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks.


RESULTS
A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P=0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients.


CONCLUSIONS
Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable.
Bengala
C
C
Division of Medical Oncology, University Hospital, University of Modena and Reggio Emilia, 41100 Modena, Italy. carmelo.bengala@unimore.it
Bertolini
F
F
Malavasi
N
N
Boni
C
C
Aitini
E
E
Dealis
C
C
Zironi
S
S
Depenni
R
R
Fontana
A
A
Del Giovane
C
C
Luppi
G
G
Conte
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib