PURPOSE:To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS:Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11 every 4 weeks. RESULTS:No unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2 months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18 months compared with historical norms (25.0% at 18 and 24 months; 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI 6.7-31.4), with improved OS rates at ≥12 months (87.5% at 12, 50.0% at 24, 34.1% at 36-60 months) compared with the historical norms. The median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months (95% CI upper bound not reached) in the methylated and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients. CONCLUSIONS:The addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

译文

目的:评估硼替佐米联合标准放射治疗(RT)和替莫唑胺(TMZ)联合佐剂硼替佐米和TMZ≤24个周期的前期治疗在新诊断为多形胶质母细胞瘤(GBM)的患者的安全性和有效性。
方法与材料:纳入24例新诊断为GBM的患者。患者在手术后3至6周开始接受标准的外部束区域RT并发TMZ,随后进行辅助TMZ和硼替佐米≤24个周期或直至肿瘤进展。在放疗期间,在第1、4、8、11、29、32、36和39天服用硼替佐米的剂量为1.3 mg / m2。在放疗之后,在1、4、8和8天服用硼替佐米的剂量为1.3mg / m2。每4周11个。
结果:添加硼替佐米未发生意外不良事件。功效分析显示中位无进展生存期(PFS)为6.2个月(95%置信区间[CI] 3.7-8.8),与历史标准相比(18和24个月为25.0%),≥18个月的PFS率很有希望; 30个月时为16.7%)。就总生存期(OS)而言,中位OS​​为19.1个月(95%CI 6.7-31.4),≥12个月时OS率有所改善(12.时为87.5%,24时为50.0%,36-60个月时为34.1% )与历史规范进行比较。 10名MGMT甲基化患者的中位PFS为24.7个月(95%CI 8.5-41.0),而13名未甲基化患者的中位PFS为5.1个月(95%CI 3.9-6.2)。甲基化患者的估计中位OS为61个月(未达到95%CI上限),未甲基化患者的估计中位OS为16.4个月(95%CI 11.8-21.0)。
结论:在新诊断的GBM患者中,将硼替佐米加到目前的标准放化疗中是可以忍受的。 PFS和OS率似乎很有希望,对MGMT甲基化患者有更多益处。有必要对更多的患者进行进一步的临床研究。

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