Woo Jong-Yun, Yang Seung Ho, Lee Youn Soo, Lee Su Youn, Kim Jeana, Hong Yong Kil
Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Department of Neurosurgery, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
J Korean Neurosurg Soc. 2015 Nov;58(5):426-31. doi: 10.3340/jkns.2015.58.5.426. Epub 2015 Nov 30.
The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor.
Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m(2)/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64).
The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was 22.7±24.1/mm(2) (mean±standard deviation), and this was lower than that of the initial tumor (61.4±32.7/mm(2)) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments.
The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.
本研究旨在评估持续低剂量替莫唑胺（TMZ）化疗对复发性及TMZ难治性多形性胶质母细胞瘤（GBM）的临床疗效，并研究其疗效与肿瘤内微血管密度之间的关系。
30例接受过Stupp方案治疗后复发的GBM患者于2007年至2013年期间每日接受50mg/m²的TMZ治疗，直至肿瘤进展。持续低剂量TMZ给药的中位持续时间为8周（范围2 - 64周）。
持续低剂量TMZ治疗的中位无进展生存期（PFS）为2个月（范围0.5 - 16个月）。6个月时，PFS为20%。从该治疗开始至死亡的中位总生存期（OS）为6个月（95%CI：5.1 - 6.9）。17例患者再次手术获取的复发肿瘤组织的微血管密度为22.7±24.1/mm²（均值±标准差），低于初始肿瘤（61.4±32.7/mm²）（p值 = 0.001）。这表明标准TMZ放化疗可降低GBM内的微血管密度，且复发发生在代谢负担低的肿瘤细胞中。在血管生成不良环境中的复发性GBM细胞中，无法预期持续低剂量TMZ的疗效。
持续低剂量TMZ化疗的疗效有限。本研究表明需要为复发性及TMZ难治性GBM制定进一步的治疗策略。
