A Phase II Study of Sagopilone (ZK 219477; ZK-EPO) in Patients With Breast Cancer and Brain Metastases

Abstract

BackgroundPatients with progressive metastatic breast cancer to the central nervous system (CNS) have limited treatment options. Patients and MethodsWe 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/m2 or 22 mg/m2 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. ResultsFifteen 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. ConclusionsSagopilone 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.