Bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines: Final results of a phase I/II study

Abstract

1072 Background: Capecitabine has shown substantial activity in taxane and/or anthracycline pretreated breast cancer patients. Bortezomib, a 26S proteasome inhibitor, has been shown to increase sensitivity to chemotherapy. This phase I/II trial was initiated to evaluate the combination of capecitabine and bortezomib in heavily pretreated patients with metastatic breast cancer. Methods: Patients with metastatic breast cancer and prior taxane and/or anthracycline therapy were treated with bortezomib (1.0–1.3 mg/m2; days 1, 4, 8 & 11) and capecitabine (1,500–2,500 mg/m2, days 1–14) in 3-weeks intervals for up to 8 cycles. Primary endpoints were to determine the optimal doses for the combination (phase I) and the tumor response rate (RR) (phase II). Secondary endpoints included safety, time to progression (TTP), duration of response (DR), and overall survival (OS). Results: A total of 35 patients were enrolled and 29 patients were assessable for response. The majority of patients had received 2 or 3 lines of chemotherapy (69% and 14%, respectively) prior to the study. The maximum tolerated doses (MTD) were bortezomib 1.3 mg/m2 and capecitabine 2500 mg/m2. Dose limiting toxicities were Grade 3 stomatitis in 1 out of 6 patients at 1.0/2,000 and Grade 3 diarrhea in 1 out of 6 patients at 1.3/2,500. Myelosuppression was low. Non-hematological toxicities were generally mild to moderate with no G4 toxicity being observed. Most common side effects were thrombocytopenia (Grade 3/4 27% of patients), diarrhea (18%), hand-foot syndrome (12%), peripheral neuropathy (12%), leucopenia (9%) and asthenia (9%). The overall RR was 17.2% and an additional 31% of patients had stable disease (31%; 4 unconfirmed). In the 21 patients treated at the MTD, RR was 17.6% and 47% of patients had SD. Median TTP and OS were 3.5 months (95% CI 1.9–4.4) and 7.5 months (95% CI 5.6–14.6), respectively. Median DR was 4.4 months. Conclusions: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated breast cancer. [Table: see text]