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Clin Colorectal Cancer. 2014 Jun;13(2):81-6. doi: 10.1016/j.clcc.2013.12.005. Epub 2014 Jan 4.

A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers.

Author information

1
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA. Electronic address: crystal.denlinger@fccc.edu.
2
Division of Hematology and Oncology, University Hospitals Case Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
3
Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA.
4
Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA.
5
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
6
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
7
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA.
8
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD.

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.

PATIENTS AND 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.

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00085410.

KEYWORDS:

Biliary tract cancers; Bortezomib; Cholangiocarcinoma; Proteosome inhibition

PMID:
24512954
PMCID:
PMC4189831
DOI:
10.1016/j.clcc.2013.12.005
[Indexed for MEDLINE]
Free PMC Article
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