A phase II study of sagopilone (ZK 219477; ZK-EPO) in patients with breast cancer and brain metastases.

UNLABELLED: Treatments for women with recurrent brain metastases from breast cancer are limited. In this phase II study,we administered sagopilone to patients with breast cancer and brain metastases. We observed modest activity with a central nervous system objective response rate of 13.3%; however, median PFS was disappointing. Further studies should focus on other agents to treat this challenging clinical problem.
BACKGROUND: Patients with progressive metastatic breast cancer to the central nervous system (CNS) have limited treatment options. PATIENTS AND METHODS: We conducted a phase II study of sagopilone, an epothilone B analogue that crosses the blood-brain barrier, in patients with breast cancer brain metastases. Women were treated with 16 mg/m(2) or 22 mg/m(2) intravenously every 21 days. The primary endpoint was CNS objective response rate (ORR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Using modified, high-resolution magnetic resonance angiography (MRA), we also evaluated changes in vessel tortuosity with treatment.
RESULTS: Fifteen women were enrolled; all had progressive CNS disease despite whole-brain radiotherapy. Two patients achieved a partial response (ORR, 13.3%) and remained in the study for 6 cycles. Responses were not associated with normalization of tumor-associated vessels on correlative imaging studies. Median PFS and OS were 1.4 months and 5.3 months, respectively. The most common grade 3 toxicities were lymphopenia and fatigue. Enrollment was stopped prematurely because of limited observed activity and slow accrual.
CONCLUSIONS: Sagopilone was associated with modest CNS activity in patients with breast cancer; however median PFS was disappointing. Further studies should examine other potentially active agents and/or combinations for this challenging clinical problem.