Low-dose temozolomide combined with valproic acid in the treatment of an elderly patient with MGMT-methylated glioblastoma and multiple comorbidities: a case report.

BACKGROUND: The prognosis for very elderly patients with glioblastoma (GBM) is extremely poor. For patients with a high tumor burden, multiple severe comorbidities, and poor physical condition, standard surgery and chemoradiotherapy are often poorly tolerated, and there is an urgent need for effective, low-toxicity palliative treatment options. CASE PRESENTATION: The patient is an 85-year-old man who presented with progressive speech difficulty. Imaging revealed a large left frontal lobe GBM measuring 6.4 cm × 6.0 cm with intratumoral hemorrhage. Molecular testing showed positive O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, wild-type IDH1/2, and negative BRAF V600E. The patient had multiple severe comorbidities, including epilepsy, congestive heart failure, type 2 diabetes mellitus, cerebral infarction, and severe malnutrition. The baseline Eastern Cooperative Oncology Group (ECOG) score was 4, and the Karnofsky Performance Status (KPS) score was 30; after systematic treatment, follow-up showed an ECOG score of 3 and a KPS score of 50. Treatment and outcome: Starting from 25 December 2024, palliative treatment was initiated with metronomic low-dose temozolomide (50 mg/day, continuous oral administration without dose reduction or interruption) combined with sodium valproate (0.4 g/dose, three times daily, administered via nasogastric tube). Concurrently, standard symptomatic and supportive treatments were given, including osmotic dehydration with mannitol and low-dose dexamethasone (corticosteroids). Because of the patient's critical condition and inability to be transported or undergo MRI, imaging efficacy evaluation was performed solely using head CT scans, and the MRI-RANO response criteria could not be applied. The regimen was well tolerated, with no myelosuppression or abnormal liver function. At the 3-month follow-up, serial head CT scans indicated stable disease without progression; ECOG and KPS scores showed significant improvement compared to baseline. CONCLUSION: Low-dose metronomic temozolomide combined with sodium valproate is a safe and feasible palliative treatment strategy for very elderly GBM patients with MGMT promoter methylation, poor physical condition, and an inability to tolerate standard therapy. This study is a single-case report, and the conclusions have limitations, requiring validation through large-sample clinical studies.