A pilot study of levetiracetam as a sensitizer of temozolomide for newly diagnosed glioblastoma: A prospective, open-label, phase II study (KBTS-1601 study).

Abstract

Background: We evaluated the survival benefit of levetiracetam as a chemosensitizer of temozolomide for patients with newly diagnosed glioblastoma. Methods: This was an open-label, multicenter, phase II study (NCT02815410). Eligible patients were aged 18 years or older and had newly diagnosed glioblastoma with an ECOG performance status of 0-2. All patients received radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles). The first dose of levetiracetam was given just after the surgery at 250mg orally twice a day and increased up to 500mg twice a day prior to radiation. This prospective study was designed to test whether levetiracetam in conjunction with temozolomide improved survival. The historical control group was based on data from a study by Gwak et al. for Korean patients with newly diagnosed glioblastoma with a median overall survival(OS) of 17.5 months and a median progression-free survival (PFS) of 10.1 months. Results: Forty-six patients were enrolled between August 2016 and January 2019. The median follow-up duration was 24.9 months (range, 7.9-35.5). All patients completed standard radiation therapy with temozolomide, and 39 (84.8%) patients completed six cycles of adjuvant temozolomide. Median overall survival (OS) was 30.0 months, and median PFS was 15.0 months. OS at 6, 12, and 24 months was 100%, 91.3%, and 60.7%, respectively. PFS at 6, 12, and 24 months was 93.2%, 65.3%, and 22.6%, respectively. Conclusions: Addition of levetiracetam during concurrent and adjuvant temozolomide along with radiotherapy in patients with newly diagnosed glioblastoma may result in improved outcomes compared to historical data and merits further study.