在阿尔伯塔省,改用替莫唑胺仿制药导致胶质瘤患者3级和4级骨髓毒性显著增加

IF 2.4 Q2 CLINICAL NEUROLOGY
Egiroh Omene, Omar Abdel-Rahman, Eugene Batuyong, Samir Patel, Roland Coppens, Jacob Easaw, Kelvin Young
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Multivariate logistic regression analysis was performed to determine association between grade 3 or 4 toxicity to generic vs. brand-name TMZ exposure, ECOG score and age. Kaplan-Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand-name and generic TMZ cohorts, as well as the cytopenic vs non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand-name TMZ after Alberta preemptively stopped generic TMZ. Results Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n=156) as compared to 3% and 5% of patients (n=100) treated with brand-name TMZ treated patients; p= 0.003 and 0.001. 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引用次数: 0

摘要

替莫唑胺(TMZ)是一种口服全身化疗药物,主要用于治疗高度胶质瘤。由于全身化疗费用的上升,许多司法管辖区已经用通用配方取代了品牌。本研究的目的是确定在加拿大阿尔伯塔省,品牌TMZ与通用TMZ治疗的患者在3级或4级骨髓毒性发生率和中位总生存期方面是否存在差异。根据初步数据显示的毒性超标,该省暂停了通用TMZ的使用。方法这项多中心回顾性研究纳入了阿尔伯塔省接受TMZ治疗的新诊断的高度胶质瘤患者的数据。进行多变量logistic回归分析,以确定3级或4级毒性对通用和品牌TMZ暴露,ECOG评分和年龄之间的关系。Kaplan-Meier生存估计和log-rank检验用于确定品牌和通用TMZ队列之间以及细胞减少与非细胞减少患者之间的总生存差异。此外,在Alberta预先停用仿制TMZ后,对所有接受品牌TMZ治疗的新生胶质瘤患者进行了3级或4级骨髓毒性筛选分析。结果3级或4级中性粒细胞减少症和血小板减少症分别在仿制TMZ治疗的患者中占15%和19% (n=156),而在名牌TMZ治疗的患者中占3%和5% (n=100);P = 0.003和0.001。通用TMZ治疗的GBM患者的中位总生存期(13.7个月)比品牌TMZ治疗的中位总生存期(15.8个月,p = 0.178.)也有增加的趋势,但符合统计学意义。基于这些结果,该省停止使用通用TMZ并恢复使用默克TMZ。自该省停用仿制药以来,对所有新发胶质瘤患者(n= 89)的初步审查显示,3级和4级中性粒细胞减少分别为3.4%和10.1%。结论:阿尔伯塔省在高级别胶质瘤患者中,毒性谱的统计学显著差异促使其将仿制TMZ替换为品牌TMZ,等待更详细的分析。我们的研究提供了证据,支持对非专利化疗的长期安全性进行前瞻性研究的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Switch to generic formulation of temozolomide results in statistically significant increase in grade 3 and 4 bone marrow toxicity in glioma patients in the province of Alberta
Abstract Background Temozolomide (TMZ) is an oral, systemic chemotherapy used chiefly for treating high grade glioma. Due to the rising costs of systemic chemotherapy, many jurisdictions have replaced brand-name with generic formulations. The aim of this study was to determine whether or not there was difference in the incidence of grade 3 or 4 bone marrow toxicity and median overall survival in patients treated with brand-name vs generic TMZ in the province of Alberta, Canada. The province suspended use of generic TMZ based on preliminary data pointing to excess toxicity. Methods This multicenter, retrospective study included data from patients with newly diagnosed high grade glioma that received treatment with TMZ in Alberta. Multivariate logistic regression analysis was performed to determine association between grade 3 or 4 toxicity to generic vs. brand-name TMZ exposure, ECOG score and age. Kaplan-Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand-name and generic TMZ cohorts, as well as the cytopenic vs non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand-name TMZ after Alberta preemptively stopped generic TMZ. Results Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n=156) as compared to 3% and 5% of patients (n=100) treated with brand-name TMZ treated patients; p= 0.003 and 0.001. A trend towards increased median overall survival in GBM patients treated with generic TMZ (13.7 months) versus brand-name (15.8 months, p = 0.178.) was also observed though meeting statistical significance. Based on these results, the province stopped the use of generic TMZ and reverted to the Merck TMZ. An initial review of all new glioma patients (n= 89) treated with Merck TMZ since the province stopped generic drug demonstrated 3.4% and 10.1% grade 3 or 4 neutropenia, and respectively. Conclusions The statistically significant difference in toxicity profile has prompted the province of Alberta to replace generic TMZ for brand-name TMZ in high grade glioma patients pending more detailed analysis. Our study provides evidence supporting the importance of conducting prospective studies on long-term safety for generic chemotherapies.
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来源期刊
Neuro-oncology practice
Neuro-oncology practice CLINICAL NEUROLOGY-
CiteScore
5.30
自引率
11.10%
发文量
92
期刊介绍: Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving
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