Localized (Z)- <i>n</i> -butylidenephthalide biodegradable wafer as surgical adjuvant in recurrent glioblastoma for extending survival and re-sensitizing chemotherapy: A compassionate use study.

Abstract

e14089 Background: Surgical resection of recurrent glioblastoma is often limited by anatomical constraints and neurological deficit risks, particularly in multi-focal disease involving bilateral hemispheres, or spinal/deep structures. Surgery adjuncts, such as (Z)- n -butylidenephthalide ((Z)-BP) wafer, act as localized therapies designed to potentiate complete resection and re-sensitize residual tumors. We report outcomes of (Z)-BP wafer in heavily pretreated recurrent glioblastoma patients with disease ineligible for trials. Methods: This compassionate use program was approved by the Research Ethics Committee and the regulatory agency. Seven recurrent glioblastoma patients (bilateral [n=2], cervical spinal [n=1], thalamic [n=1], and supratentorial lesions [n=3] with exhausted standard treatments. Results: Safety profile aligned with prior Phase I results, supporting tolerability of up to six wafers (total 450 mg (Z)-BP). No seizures, brain edema, or wound issues were observed in this program. Treatment-emergent adverse events included surgery-related anemia (57.1%) and lymphocyte reduction (42.9%), and alanine aminotransferase increased (42.9%). Grade 3 events comprised decreased CD4 and total lymphocytes (28.6% each), attributable to surgery. Efficacy analysis demonstrated median overall survival of 14.5 (range 3.7-49.9) months. Response assessment revealed two partial response and five stable disease cases (100% control rate). Patients also maintained their performance status (Karnofsky and Modified Ashworth scores). Notably, resected tumor tissue analysis from one patient revealed a shift in O 6 -methylguanine-DNA methyltransferase promoter status from unmethylated to intermediate methylation. Conclusions: This study provides evidences that (Z)-BP wafer improves survival in heavily pretreated patients. The median survival of 14.5 months exceeding historical controls by 6-9 months, combined with favorable tolerability, epigenetic methylation changes, and preserved performance, supports further investigation. A randomized Phase IIb/III trial has been initiated to validate these findings with overall survival.