CCNU与替莫唑胺联合用于新诊断的启动子甲基化野生型胶质母细胞瘤的首次多中心真实世界经验。

First multicentric real-life experience with the combination of CCNU and temozolomide in newly diagnosed promoter methylated wildtype glioblastoma.

作者信息

Lazaridis Lazaros, Bumes Elisabeth, Cäcilia Spille Dorothee, Schulz Tim, Heider Sina, Agkatsev Sarina, Schmidt Teresa, Blau Tobias, Oster Christoph, Feldheim Jonas, Stummer Walter, Kessler Almuth Friederike, Seidel Clemens, Grauer Oliver, Hau Peter, Sure Ulrich, Keyvani Kathy, Herrlinger Ulrich, Kleinschnitz Christoph, Stuschke Martin, Herrmann Ken, Deuschl Cornelius, Breuer Stella, Hattingen Elke, Scheffler Björn, Kebir Sied, Glas Martin

机构信息

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.

出版信息

Neurooncol Adv. 2022 Aug 24;4(1):vdac137. doi: 10.1093/noajnl/vdac137. eCollection 2022 Jan-Dec.

DOI:10.1093/noajnl/vdac137

PMID:36284931

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9583686/

Abstract

BACKGROUND

The randomized phase 3 CeTeG/NOA-09 trial assessed whether CCNU plus temozolomide was superior to temozolomide alone in newly diagnosed promoter methylated glioblastoma patients. Survival was significantly improved from 31.4 months (temozolomide) to 48.1 months (CCNU plus temozolomide). In view of this encouraging data, we assessed safety and efficacy of this regimen under real-life conditions.

METHODS

We retrospectively collected clinical and radiographic data from adult newly diagnosed promoter methylated wildtype glioblastoma patients from five neuro-oncology centers in Germany. For inclusion in our analysis, treatment with CCNU and temozolomide had to be performed for at least six weeks (one course).

RESULTS

Seventy patients were included. Median progression-free survival was 14.4 months and median overall survival 33.8 months. Patients with TTFields treatment for at least 8 weeks and CCNU plus temozolomide ( = 22, 31%) had a prolonged progression-free survival compared to those with TTFields treatment for less than eight weeks ( = 48, 69%) (21.5 versus 11.2 months; = .0105). In a multivariable Cox regression analysis, TTFields treatment for eight weeks or longer together with CCNU plus temozolomide and a Karnofsky performance score ≥ 90% were independent prognostic factors for progression-free and overall survival. Pseudoprogression occurred in = 16 (33%) of investigated = 49 (70%) patients. In = 31 (44%) patients high-grade hematotoxicity was observed.

CONCLUSIONS

The results from this multicentric trial indicate that-under real-life conditions-toxicity and survival estimates are comparable to the CeTeG/NOA-09 trial. TTFields therapy for at least eight weeks in combination with this regimen was independently associated with prolonged survival.

摘要

背景

随机3期CeTeG/NOA-09试验评估了洛莫司汀联合替莫唑胺在新诊断的启动子甲基化胶质母细胞瘤患者中是否优于单纯使用替莫唑胺。生存期从31.4个月（替莫唑胺组）显著延长至48.1个月（洛莫司汀联合替莫唑胺组）。鉴于这些令人鼓舞的数据，我们评估了该方案在实际临床条件下的安全性和疗效。

方法

我们回顾性收集了来自德国五个神经肿瘤中心的成年新诊断的启动子甲基化野生型胶质母细胞瘤患者的临床和影像学数据。纳入我们分析的患者，洛莫司汀和替莫唑胺治疗必须至少持续六周（一个疗程）。

结果

共纳入70例患者。中位无进展生存期为14.4个月，中位总生存期为33.8个月。接受替莫唑胺治疗至少8周并联合洛莫司汀和替莫唑胺的患者（n = 22，31%）与接受替莫唑胺治疗少于8周的患者（n = 48，69%）相比，无进展生存期延长（21.5个月对11.2个月；P = 0.0105）。在多变量Cox回归分析中，替莫唑胺治疗8周或更长时间联合洛莫司汀和替莫唑胺以及卡诺夫斯基表现评分≥90%是无进展生存期和总生存期的独立预后因素。49例（70%）接受研究的患者中有16例（33%）出现假性进展。31例（44%）患者观察到重度血液毒性。