title: Continuous Low-Dose Temozolomide Chemotherapy and Microvessel Density in Recurrent Glioblastoma.
abstract: 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/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).
  
  
  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/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jong-Yun
authors.initials: JY
authors.lastname: Woo
authors.affiliation: Department of Neurosurgery, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Hospital Pathology, Bucheon St.Mary's Hospital, The Catholic University of Korea, Bucheon, Korea.
authors.forename: Jeana
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yong Kil
authors.initials: YK
authors.lastname: Hong
keywords: Glioblastoma; Metronomic chemotherapy; Microvessel density; Temozolomide