Wick Antje, Felsberg Jörg, Steinbach Joachim P, Herrlinger Ulrich, Platten Michael, Blaschke Britta, Meyermann Richard, Reifenberger Guido, Weller Michael, Wick Wolfgang
Department of Neurooncology, University of Heidelberg, Heidelberg, Germany.
J Clin Oncol. 2007 Aug 1;25(22):3357-61. doi: 10.1200/JCO.2007.10.7722.
Evaluation of toxicity and efficacy of an alternating weekly regimen of temozolomide administered 1 week on and 1 week off in patients with recurrent glioma.
Ninety adult patients with recurrent gliomas accrued in one center received chemotherapy with temozolomide at 150 mg/m(2)/d (days 1 through 7 and 15 through 21 every 4 weeks) with individual dose adjustments according to hematologic toxicity.
A total of 906 treatment weeks were delivered. Grade 4 hematotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0) was observed in 24 treatment weeks (2.6%). CTCAE grade 4 lymphopenia eventually developed in 11 patients (12%). There were neither cumulative lymphopenias nor opportunistic infections. The progression-free survival (PFS) rate at 6 months for glioblastoma patients was 43.8%. The median PFS in these patients was 24 weeks (95% CI, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (log-rank P = .37).
These data imply that the alternating weekly schedule is feasible, safe, and effective and clearly warrants investigation in randomized studies. Compared with more protracted low-dose temozolomide schedules, the 1-week-on/1-week-off schedule may be less toxic. We provide preliminary evidence that this dose-dense schedule is also active in patients with tumors lacking MGMT gene promoter methylation.
评估替莫唑胺每周交替给药方案（给药1周，停药1周）用于复发性胶质瘤患者的毒性和疗效。
在一个中心招募的90例成年复发性胶质瘤患者接受替莫唑胺化疗，剂量为150mg/m²/d（每4周的第1至7天和第15至21天），并根据血液学毒性进行个体化剂量调整。
共进行了906个治疗周。根据不良事件通用术语标准（CTCAE；第3.0版），在24个治疗周（2.6%）观察到4级血液毒性。最终有11例患者（12%）出现CTCAE 4级淋巴细胞减少。既没有累积性淋巴细胞减少，也没有机会性感染。胶质母细胞瘤患者6个月时的无进展生存率（PFS）为43.8%。这些患者的中位PFS为24周（95%CI，17至26周），从进展诊断开始的中位生存时间为38周（95%CI，30至46周），从进展开始的1年生存率为23%。肿瘤组织中的O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子甲基化与更长的PFS无关（对数秩检验P = 0.37）。
这些数据表明每周交替给药方案可行、安全且有效，显然值得在随机研究中进行调查。与更长期的低剂量替莫唑胺方案相比，1周给药/1周停药方案的毒性可能较小。我们提供了初步证据，表明这种剂量密集方案对缺乏MGMT基因启动子甲基化的肿瘤患者也有活性。
