Sher David J, Henson John W, Avutu Bindu, Hochberg Fred H, Batchelor Tracy T, Martuza Robert L, Barker Fred G, Loeffler Jay S, Chakravarti Arnab
Harvard Radiation Oncology Program, Boston, MA, USA.
J Neurooncol. 2008 May;88(1):43-50. doi: 10.1007/s11060-008-9530-8. Epub 2008 Jan 30.
Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM.
We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS).
Forty-three patients (group 1, n = 21; group 2, n = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients (P < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P = 0.08) despite modest patient numbers.
Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting.
替莫唑胺(TMZ)与放疗(RT)同时使用并在其后作为辅助单一疗法,已使多形性胶质母细胞瘤(GBM)患者的生存率得到提高。然而,其主要作用机制是通过增强放射反应、独立的细胞毒性,还是两者兼有,尚不清楚。我们试图确定在新诊断的GBM患者中,同步和辅助使用替莫唑胺与单独辅助使用替莫唑胺相比,同步使用替莫唑胺的相对贡献。
我们确定了2002年至2004年间在麻省总医院被诊断为GBM并接受手术、累及野放疗和化疗的患者。符合条件的患者要么单独接受辅助替莫唑胺治疗(第1组),要么在放疗时同步使用替莫唑胺,随后接受辅助替莫唑胺治疗(第2组)。这项回顾性分析的主要终点是总生存期(OS)。
本研究纳入了43例患者(第1组,n = 21;第2组,n = 22)。存活患者的中位随访时间为33.7个月。这两组患者的基线特征无显著差异。单因素分析显示,接受同步和辅助替莫唑胺治疗的患者2年总生存率为51%,中位生存期为25.5个月,而第1组患者的2年总生存率为36%,中位生存期为15.6个月(P < 0.05)。多因素分析显示,尽管患者数量较少,但支持同步使用替莫唑胺的风险比(HR)有趋于显著的趋势(HR = 0.51,P = 0.08)。
与单独辅助使用替莫唑胺相比,同步和辅助使用替莫唑胺可提高生存率,突出了替莫唑胺在临床环境中对放射效应的增强作用。