Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy

Inclusion criteria

• Recursive Partitioning Analysis (RPA), Class I ~ Class II
• Karnofsky Performance Status of ≥70
• The primary tumor must be pathologically confirmed. For newly diagnosed brain metastases, the number of metastases is not limited, but the brain metastases could not have been within 5 mm of hippocampus. Additionally, there must be no hard or soft meningeal metastases.
• No history of whole-brain radiation therapy; patients who are eligible for surgical resection of brain metastases prior to radiation therapy are allowed.
• Bone marrow function: White blood cell count ≥ 4 × 10⁹/L, hemoglobin ≥ 90 g/L, and platelet count ≥ 100 × 10⁹/L.
• Adequate hepatic function: Total bilirubin ≤ 1.5 × ULN (Upper Limit of Normal); ALT (alanine aminotransferase), AST (aspartate aminotransferase) ≤ 2.5 × ULN; ALP (alkaline phosphatase) ≤ 2.5 × ULN and total bilirubin ≤ ULN.
• Adequate renal function: creatinine clearance rate ≥ 30 ml/min.
• Patients or their legal guardians voluntarily participate and sign the informed consent form.

Exclusion criteria

• Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt.
• Planned cytotoxic chemotherapy during the WBRT.
• Pregnant or lactating women (Women of childbearing age must undergo a pregnancy test; effective contraception must be enforced during the treatment period).
• Previous cranial radiation therapy (Except for patients with head and neck cancer where the disease site is outside the cranial radiation field).
• Severe or active symptomatic cardiopulmonary diseases; clinically significant psychiatric disorders; Personality or psychiatric disease; Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease;
• Intolerant to or allergic to Memantine or pioglitazone.
• Difficulty swallowing, chronic diarrhea, or bowel obstruction.
• NYHA class III or IV heart failure or symptomatic peripheral edema (grade 2 or higher); those treated with insulin or oral hypoglycemic agents for steroid-induced hyperglycemia, or those currently using other NMDA antagonists.