BACKGROUND: Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles. RESULTS: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months. CONCLUSION: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.
BACKGROUND: Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles. RESULTS: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months. CONCLUSION: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.
Authors: Marci D Jones; Julie C Liu; Thomas K Barthel; Sadiq Hussain; Erik Lovria; Dengfeng Cheng; Jesse A Schoonmaker; Sudhanshu Mulay; David C Ayers; Mary L Bouxsein; Gary S Stein; Siddhartha Mukherjee; Jane B Lian Journal: Clin Cancer Res Date: 2010-09-15 Impact factor: 12.531
Authors: William J Irvin; Robert Z Orlowski; Wing-Keung Chiu; Lisa A Carey; Frances A Collichio; Philip S Bernard; Inge J Stijleman; Charles Perou; Anastasia Ivanova; E Claire Dees Journal: Clin Breast Cancer Date: 2010-12-01 Impact factor: 3.225
Authors: Bhaskar C Das; Pritam Thapa; Radha Karki; Caroline Schinke; Sasmita Das; Suman Kambhampati; Sushanta K Banerjee; Peter Van Veldhuizen; Amit Verma; Louis M Weiss; Todd Evans Journal: Future Med Chem Date: 2013-04 Impact factor: 3.808
Authors: Ansgar Brüning; Petra Burger; Marianne Vogel; Martina Rahmeh; Klaus Friese; Miriam Lenhard; Alexander Burges Journal: Invest New Drugs Date: 2008-11-28 Impact factor: 3.850