Skardelly Marco, Dangel Elena, Gohde Julia, Noell Susan, Behling Felix, Lepski Guilherme, Borchers Christian, Koch Marilin, Schittenhelm Jens, Bisdas Sotirios, Naumann Aline, Paulsen Frank, Zips Daniel, von Hehn Ulrike, Ritz Rainer, Tatagiba Marcos Soares, Tabatabai Ghazaleh
Department of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
Department of Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
Oncologist. 2017 May;22(5):570-575. doi: 10.1634/theoncologist.2016-0347. Epub 2017 Mar 30.
The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS).
In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded.
Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, = .46).
Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.
在新诊断的胶质母细胞瘤（GBM）中，替莫唑胺（TMZ）维持治疗延长超过六个周期的影响仍是一个讨论话题。我们研究了延长TMZ维持治疗对无进展生存期（PFS）和总生存期（OS）的影响。
在这项回顾性单中心队列研究中，我们纳入了接受放疗并联合及辅助TMZ治疗的GBM患者。为进行分析，纳入了完成六个TMZ维持周期的患者（B组）、TMZ治疗超过六个周期的患者（C组）或在前六个周期内停止TMZ维持治疗的患者（A组）。排除在前六个TMZ维持周期内病情进展的患者。
107例患者的临床数据纳入Kaplan-Meier分析，102例纳入Cox回归分析。A组的中位PFS时间为8.1个月（95%置信区间[CI]6.1 - 12.4），B组为13.7个月（95%CI 10.6 - 17.5），C组为20.9个月（95%CI 15.2 - 43.5）。在首次病情进展时，B组TMZ/洛莫司汀再激发的缓解率为47%，C组为13%。A组的中位OS时间为12.7个月（95%CI 10.3 - 16.8），B组为25.2个月（95%CI 17.7 - 55.5），C组为28.6个月（95%CI 24.4 - 无上限）。然而，对C组与B组患者进行多因素Cox回归分析，校正其他风险因素的不平衡后，OS的相对风险（RR）无差异（RR 0.77，P = 0.46）。
我们的数据不支持将TMZ维持治疗普遍延长超过六个周期。2017年；22：570 - 575 对实践的启示：放疗联合及辅助替莫唑胺（TMZ）维持治疗仍是新诊断的65岁以下胶质母细胞瘤患者的标准治疗方案。然而，在临床实践中，许多中心将TMZ维持治疗延长超过六个周期。这种延长的影响存在争议，且尚未在前瞻性随机临床试验中得到解决。我们通过多因素分析比较了超过六个周期的TMZ与恰好六个周期的TMZ对总生存期（OS）和无进展生存期（PFS）的影响，发现对PFS有益，但对OS无益。因此，我们的数据不建议将TMZ维持治疗延长超过六个周期，这在神经肿瘤学实践中应予以考虑。
