A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

Abstract

Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40\u2009Gy in 15 fractions vs. 60\u2009Gy in 30 fractions, 34\u2009Gy in 10 fractions vs. 60\u2009Gy in 30 fractions, and 40\u2009Gy in 15 fractions vs. 25\u2009Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40\u2009Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25\u2009Gy in 5 fractions with concomitant (150\u2009mg/m2/day, 5\u2009days) and adjuvant temozolomide over 40\u2009Gy in 15 fractions with concomitant (75\u2009mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4\u2009years and follow-up will last 2\u2009years. Patients 71\u2009years of age or older, or 71–75\u2009years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. Discussion If the primary endpoint is met, short-course radiotherapy comprising 25\u2009Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. Trial registration Registry number: jRCTs031200099. Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.