Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study.
Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study.
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DOI：
10.1093/noajnl/vdab041
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Campian JL
中科院分区：
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作者：
Damato AR;Luo J;Katumba RGN;Talcott GR;Rubin JB;Herzog ED;Campian JL
时间疗法是一种创新的方法，通过根据患者的日常节律定时提供抗癌治疗来提高生存率。替莫唑胺（TMZ）是用于胶质母细胞瘤（GBM）的标准护理化疗剂。TMZ给药的时间是否影响GBM患者的结局以前尚未研究。我们试图评估维持TMZ时辰疗法对GBM患者生存的影响。这项回顾性研究回顾了2010年1月1日至2018年12月31日在华盛顿大学医学院接受手术、放化疗并在早晨或晚上服用TMZ的新诊断GBM患者。采用Kaplan-Meier法和考克斯回归模型进行总生存期（OS）分析。倾向评分法解释了潜在的观察性研究偏倚。在违反比例风险假设的情况下，采用限制平均生存时间（RMST）方法。我们分析了166例符合条件的GBM患者，中位随访时间为5.07年。与晚间相比，早晨服用TMZ的患者表现出更长的OS（中位OS，95%置信区间[CI] = 1.43，1.12-1.92 vs 1.13，0.84-1.58年），第1年RMST差异显著（-0.09，95% CI：-0.16至-0.018）。在MGMT甲基化患者中，AM患者的中位OS延长6个月，第1年（−0.13，95%CI = −0.24至−0.019）至2.5年（−0.43，95%CI = −0.84至−0.028）的RMST差异显著。在调整混杂因素后，RMST差异回归支持所有患者在第1、2和5年的早晨TMZ的优势（均P <0.05）。我们的研究提供了TMZ时间疗法对GBM患者生存有益的初步证据。这种影响在MGMT甲基化患者中更为明显。
Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan–Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12–1.92 vs 1.13, 0.84–1.58 years) with a significant year 1 RMST difference (−0.09, 95% CI: −0.16 to −0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (−0.13, 95% CI = −0.24 to −0.019) to 2.5 (−0.43, 95% CI = −0.84 to −0.028). Superiority of morning TMZ at years 1, 2, and 5 (all P < .05) among all patients was supported by RMST difference regression after adjusting for confounders. Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients.