title: A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers.
abstract: BACKGROUND
  Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest that proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers.
  
  
  METHODS
  Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0 to 2 previous therapies received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. The primary end point was objective response rate. A Simon 2-stage design was used (null response rate of < 5% and response rate of ≥ 20% of interest).
  
  
  RESULTS
  Twenty patients enrolled (bile duct/gallbladder cancer [14/6] and previous treatments 0/1/2 [10/6/3]). The trial was discontinued early because of lack of confirmed partial responses. No unanticipated adverse events were noted. There was 1 unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% confidence interval [CI], 0.7-77.6 months). Median survival was 9 months (95% CI, 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%, respectively. There was no difference in survival based on primary disease site.
  
  
  CONCLUSIONS
  Single-agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA. Electronic address: crystal.denlinger@fccc.edu.
authors: Crystal S
authors: CS
authors: Denlinger
authors: Division of Hematology and Oncology, University Hospitals Case Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
authors: Neal J
authors: NJ
authors: Meropol
authors: Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA.
authors: Tianyu
authors: T
authors: Li
authors: Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.
authors: Nancy L
authors: NL
authors: Lewis
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors: Paul F
authors: PF
authors: Engstrom
authors: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors: Louis M
authors: LM
authors: Weiner
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors: Jonathan D
authors: JD
authors: Cheng
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors: R Katherine
authors: RK
authors: Alpaugh
authors: Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA.
authors: Harry
authors: H
authors: Cooper
authors: Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD.
authors: John J
authors: JJ
authors: Wright
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors: Steven J
authors: SJ
authors: Cohen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib
keywords: Biliary tract cancers; Bortezomib; Cholangiocarcinoma; Proteosome inhibition