A phase I/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines

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Abstract
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/m2 on days 1, 4, 8 and 11) and capecitabine (1500–2500 mg/m2 on days 1–14) in 3-week intervals for up to eight cycles. Results: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m2 and capecitabine 2500 mg/m2. 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.