FCCC LOGO Faculty Publications
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
Clin Colorectal Cancer. 2014 Jun;13(2) :81-6
PMID: 24512954    PMCID: PMC4189831    URL: https://www.ncbi.nlm.nih.gov/pubmed/24512954
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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.
Denlinger, Crystal S Meropol, Neal J Li, Tianyu Lewis, Nancy L Engstrom, Paul F Weiner, Louis M Cheng, Jonathan D Alpaugh, R Katherine Cooper, Harry Wright, John J Cohen, Steven J eng P30 CA006927/CA/NCI NIH HHS/ Clinical Trial, Phase II Research Support, N.I.H., Extramural Clin Colorectal Cancer. 2014 Jun;13(2):81-6. doi: 10.1016/j.clcc.2013.12.005. Epub 2014 Jan 4.