Schmidt Teresa, Agkatsev Sarina, Feldheim Jonas, Oster Christoph, Blau Tobias, Sure Ulrich, Keyvani Kathy, Kleinschnitz Christoph, Stuschke Martin, Herrmann Ken, Deuschl Cornelius, Scheffler Björn, Kebir Sied, Glas Martin, Lazaridis Lazaros
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Division of Clinical Neurooncology, University Medicine Essen, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site University Medicine Essen, Essen, Germany.
DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner Site, University Medicine Essen, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK); German Cancer Research Center (DKFZ), Heidelberg, Germany.
Neurooncol Adv. 2023 Jul 20;5(1):vdad090. doi: 10.1093/noajnl/vdad090. eCollection 2023 Jan-Dec.
Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.
We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control.
A total of = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, = .0003) were significantly prolonged compared to the control cohort ( = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events ( = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event ( = 11/15, 73%).
This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.
胶质母细胞瘤复发时的标准治疗方案仍未明确界定。少数研究表明，曲磷酰胺联合依托泊苷的方案在儿童胶质母细胞瘤患者中可能可行。在这项回顾性分析中，我们确定了曲磷酰胺联合依托泊苷治疗成年胶质母细胞瘤患者疾病复发时的耐受性和可行性。
我们收集了接受曲磷酰胺和依托泊苷联合治疗超过四周（一个疗程）的成年进展性胶质母细胞瘤患者的临床病理数据。一组由研究者酌情进行经验性治疗的患者作为对照，这些患者在肿瘤实体和典型预后因素方面保持平衡。
共有22例进展性胶质母细胞瘤患者符合本分析条件。与对照组（17例）相比，无进展生存期（3.1个月对2.3个月，HR：1.961，95%CI：0.9724 - 3.9560，P = 0.0274）和总生存期（9.0个月对5.7个月，HR：4.687，95%CI：2.034 - 10.800，P = 0.0003）显著延长。在多变量Cox回归分析中，曲磷酰胺联合依托泊苷治疗成为无进展生存期和总生存期的显著预后标志物。我们在22例患者中的16例（73%）观察到高级别不良事件，血液毒性是主要的不良事件（16例中的15例，94%）。淋巴细胞减少是迄今为止最常观察到的血液毒性不良事件（15例中的11例，73%）。
本研究首次表明曲磷酰胺联合依托泊苷在成年胶质母细胞瘤患者中是安全的。观察到的生存结果可能提示潜在的有益效果。我们的数据为在前瞻性试验中对更大队列进行随访提供了合理依据。
