Journal Article

Levetiracetam as a sensitizer of concurrent chemoradiotherapy in newly diagnosed glioblastoma: An open‐label phase 2 study

Hwang, Kihwan, Chang, Jong Hee, Choi, Byung Se, Hong, Yong‐Kil, Kim, Jeong Hoon, Jung, Tae‐Young, Kang, Shin‐Hyuk, Kim, Tae Min, Kim, Junhyung, Kim, Se‐Hyuk, Kim, Yu Jung, Kang, Seok‐Gu, Kim, Chae‐Yong

2022

Overview

Background An open‐label single‐arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma. Methods Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Levetiracetam was given at 1,000–2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6‐month progression‐free survival (6mo‐PFS) and 24‐month overall survival (24mo‐OS), respectively. Outcomes of the study group were compared to those of an external control group. Results Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo‐PFS, 84.9% vs. 72.3%, p = 0.038; 24mo‐OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score‐matched analysis (6mo‐PFS, 88.0% vs. 76.9%, p = 0.071; 24mo‐OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam. Conclusions The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted. Patients aged less than 65 years exhibited better outcomes with levetiracetam. Patients with unmethylated MGMT promoter possibly have greater benefits from levetiracetam.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adult / Aged / anti‐epileptic drug / Biopsy / Brain cancer / Brain Neoplasms - diagnosis / Brain Neoplasms - genetics / Brain Neoplasms - mortality / Brain Neoplasms - therapy / Cancer therapies / Chemoradiotherapy / Chemoradiotherapy - methods / Chemotherapy / Clinical Cancer Research / concurrent chemoradiotherapy / Convulsions & seizures / Dehydrogenases / DNA Modification Methylases - genetics / DNA Repair Enzymes - genetics / Drug dosages / drug repurposing / Etiracetam / Female / Glioblastoma / Glioblastoma - diagnosis / Glioblastoma - genetics / Glioblastoma - mortality / Glioblastoma - therapy / Humans / Kaplan-Meier Estimate / levetiracetam / Levetiracetam - therapeutic use / Male / Medical prognosis / Middle Aged / Oncology / Patients / Population studies / Prescription drugs / Progression-Free Survival / Propensity Score / Radiation therapy / Republic of Korea / Survival / Tumor Suppressor Proteins - genetics