Feasibility of first-line lomustine-temozolomide (CCNU/TMZ) in elderly patients with MGMT-methylated glioblastoma: A multicenter retrospective cohort study

Abstract Background The CeTeG/NOA-09 trial showed improved survival with lomustine (CCNU) plus temozolomide (TMZ) over TMZ alone in O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated glioblastoma patients aged 18-70 years. Data on feasibility, tolerability, and outcomes in patients over 70 receiving this regimen are lacking and were evaluated in this study. Methods We conducted a retrospective multicenter cohort study including patients aged >70 years with newly diagnosed, histologically confirmed, MGMT promoter-methylated glioblastoma treated with first-line radiotherapy and CCNU/TMZ. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events v5.0. Results Eighteen patients (median age of 72 years, range 71-78) were included. Most patients had a good clinical status (median Karnofsky Performance Status of 90%, interquartile range [IQR] 80-90). Patients received a median of 5.5 (IQR 3.5-6) TMZ and 5 (IQR 3-6) CCNU cycles. Hematotoxicity occurred in 50% of patients, with grade ≥3 hematotoxicity in 33%. Hepatotoxicity was observed in two cases (11%), both grade 3. Toxicity-related treatment discontinuation occurred in 11%, with no treatment-related deaths. Median follow-up was 15.8 months (range: 4-82.5), median PFS was 11.5 months (95% CI, 8.9-21.1), and median OS was 19.1 months (95% CI, 13.3-46.4). Conclusions In this highly selected multicenter cohort of patients with MGMT promoter-methylated glioblastoma, first-line CCNU/TMZ combined with radiotherapy was feasible and tolerable. Survival outcomes were encouraging but descriptive, warranting prospective studies that include geriatric assessment before broader implementation in elderly patients.