A phase II study evaluating systemic sagopilone (ZK-EPO) treatment in patients with recurrent malignant gliomas

Abstract

2083 Background: Sagopilone (ZK-EPO) is a fully synthetic epothilone that exhibits activity in MDR tumors, and has demonstrated antitumor activity in orthotopic human glioma models in vivo. This 2-arm, phase II study aims to evaluate the safety and efficacy of sagopilone in patients (pts) with pretreated, recurrent malignant glioma who have received 2 or ≥3 prior lines of therapy, respectively. Methods: Sagopilone (16 mg/m2) was administered iv for 3 h every 21 d. The primary end point was 6-month progression- free survival (PFS-6), and secondary end points were safety, toxicity, and response rate. MRI evaluations (McDonald criteria) were performed every 2 cycles and toxicity was evaluated using CTCAE 3.0. Clinical and electrophysiological tests were undertaken before the 1st and at the 3rd and 6th cycle. Data are presented from a protocoled independent analysis of ≥3-line arm. Results: A total of 15 pts with recurrent malignant gliomas (glioblastoma multiforme [n=11] or anaplastic astrocytoma [n=4]) who had received prior surgery, radiotherapy, and ≥3 lines of chemotherapy (temozolomide/BCNU) were recruited. A median of 4 (1–6) cycles was administered and 3 pts are still receiving treatment. No objective responses were observed but stable disease of >6 wks was reported in 9 pts. Median TTP was 13 wks (1.3 to 38 wks) and 5/15 pts (target 3 pts) reached PFS-6, excluding a lower rate of 12%, although in the absence of a control arm this may be a self- selecting group and requires confirmation. The most frequent AE was neuropathy, which improved after treatment cessation. Grade 3/4 peripheral neuropathy occurred in 4 pts, with 1 requiring morphine treatment for neuropathy affecting their activities. Neuropathy presented as a mixture of paresthesia and dysesthesia, typically in a stocking distribution. Electromyography assessments showed axonal sensorimotor polyneuropathy with slight reductions of sensory action potential consistent with a primarily sensory defect. Only 1 pt had grade 4 toxicity (prolonged neutropenia) during the 1st cycle. Conclusions: Sagopilone demonstrated an acceptable safety profile and clinically relevant activity in pts with pretreated, recurrent malignant gliomas. The study continues in the 2nd-line arm and mature data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering