title: A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer.
abstract: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients.
  
  
  
  Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration.
  
  
  
  Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration.
  
  
  
  Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h.
  
  
  
  ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010.
authors.affiliation: Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Bang-Bin
authors.initials: BB
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Lu
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Ching-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Wei-Wu
authors.initials: WW
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.|Department of Radiology, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Yu
authors.affiliation: Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Shwu-Yuan
authors.initials: SY
authors.lastname: Wei
authors.affiliation: Department of Oncology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.affiliation: Department of Medical Imaging and Radiology, National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan. ttfshih@ntu.edu.tw.|Department of Medical Imaging, Taipei City Hospital, Taipei City, Taiwan. ttfshih@ntu.edu.tw.
authors.forename: Tiffany Ting-Fang
authors.initials: TT
authors.lastname: Shih
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003287:Contrast Media / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D000068258:Bevacizumab; D005047:Etoposide; D002945:Cisplatin
keywords: Bevacizumab; Breast cancer; Chemotherapy; DCE-MRI