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Denlinger CS, Meropol NJ, Li T, Lewis NL, Engstrom PF, Weiner LM, Cheng JD, Alpaugh RK, Cooper H, Wright JJ, Cohen SJ
A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients With Advanced Biliary Tract Cancers
Clinical Colorectal Cancer (2014) 13:81-86.
Therapeutic options in advanced biliary tract cancers are limited. We evaluated bortezomib in 20 patients with advanced biliary tract cancers in a single-arm phase H study. Although no objective responses were seen, 9 patients achieved stable disease with encouraging median time to progression and survival rates, suggesting that evaluation of bortezomib in combination with other therapies is warranted in this disease. 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.(C) 2014 Elsevier Inc. All rights reserved.
Publication Date: 2014-06-01.
PMCID: Pmc4189831
Last updated on Wednesday, July 08, 2020