Cisplatin and Alternating Temozolomide in Recurrent High-Grade Gliomas: Efficacy and the Role of Tumor-Infiltrating Lymphocytes in a Phase II Clinical Trial

顺铂和替莫唑胺交替治疗复发性高级别胶质瘤:II期临床试验中的疗效及肿瘤浸润淋巴细胞的作用

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Abstract

BACKGROUND: To evaluate the efficacy and safety of cisplatin combined with alternating temozolomide (TMZ) for recurrent high-grade glioma, as current treatments lack standardized protocols and predictive markers. METHODS: This study evaluated cisplatin (20 mg/m(2) IV, days 1-3) and TMZ (125 mg/m(2) orally, days 1-7 and 15-21) in 35 patients, using the RANO criteria with 6-month progression-free survival (PFS-6) as the primary endpoint. The Kaplan-Meier analysis was applied for survival, and tumor molecular profiles were retrospectively assessed. RESULTS: A median follow-up time was 61.2 months. The PFS-6 rate was 45.2%, and the median time to progression was 5.07 months. Four patients showed partial response, 16 had stable disease, and 11 had disease progression, with predominantly grade I to II toxicities. Low CD8+ tumor-infiltrating lymphocytes (TILs) correlated with improved disease control (P = .031). Data from the CGGA showed that low CD8+ TILs were associated with better survival, while high CD8+ TILs indicated increased immune response and higher immune checkpoint expression, including programmed death 1 (PD-1). CONCLUSIONS: The cisplatin plus alternating TMZ regimen is feasible and safe for recurrent high-grade gliomas, with low CD8+ TILs potentially predicting favorable responses.

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