Division of Clinical Neurooncology, Department of Neurology and Center of Integrated Oncology (CIO), University Hospital Bonn, Venusberg-Campus 1, 53105, Bonn, Germany.
Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany.
J Neurooncol. 2023 Jan;161(1):147-153. doi: 10.1007/s11060-022-04203-4. Epub 2023 Jan 7.
In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population.
Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy.
HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE.
Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures.
NCT01149109.
在随机 III 期临床试验 CeTeG/NOA-09 中，替莫唑胺（TMZ）/洛莫司汀（CCNU）联合治疗在新诊断的 MGMT 甲基化胶质母细胞瘤中优于 TMZ，尽管报告的血液毒性更高。在这里，我们分析了试验人群中的高级别血液毒性及其预后相关性。
根据不良事件通用术语标准，版本 4.0 对血液毒性不良事件≥3 级（HAE）进行描述性和比较分析。在里程碑分析中评估 HAE 与生存的相关性。进行逻辑回归分析以预测化疗同期的 HAE。
CCNU/TMZ 和 TMZ 治疗组分别有 36.4%和 28.6%的患者发生 HAE。首次 HAE 的中位发病时间发生在化疗同期（即首次 CCNU/TMZ 疗程或每日 TMZ 治疗），接受进一步疗程的 HAE 患者中有 42.9%出现重复 HAE。治疗组之间的 HAE 持续时间中位数相似（CCNU/TMZ 为 11.5 天；TMZ 为 13 天）。由于 HAE，CCNU/TMZ 组的化疗更常被中断（19.7%比 6.3%，p=0.036）。HAE 的发生与生存差异无关（p=0.76）。回归分析证实年龄较大（OR 1.08）和女性（OR 2.47）是 HAE 的预测因素，但不是治疗臂。
年龄较大和女性与 HAE 的发生率较高相关。尽管 HAE 的发生与较短的生存无关，但对高危患者进行可靠预测可能有助于优化治疗管理和支持措施的分配。
NCT01149109。
