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KMID : 1001920150580050426
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Journal of Korean Neurosurgical Society
2015 Volume.58 No. 5 p.426 ~ p.431
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Continuous Low-Dose Temozolomide Chemotherapy and Microvessel Density in Recurrent Glioblastoma
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Woo Jong-Yun
Yang Seung-Ho
Lee Youn-Soo
Lee Su-Youn
Kim Jea-Na
Hong Yong-Kil
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Abstract
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Objective: 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.
Methods: Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at 50 mg/m2/day until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64).
Results: 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/mm2 (mean±standard deviation), and this was lower than that of the initial tumor (61.4±32.7/mm2) (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.
Conclusion: 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.
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KEYWORD
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Glioblastoma, Temozolomide, Metronomic chemotherapy, Microvessel density.
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