title: MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.
abstract: BACKGROUND
  Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis.
  
  
  OBJECTIVE
  To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.
  
  
  METHODS
  Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA.
  
  
  RESULTS
  There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC < median, n= 10), former group showed a significant improvement in the median progression-free survival compared with latter group (636 vs. 196 days, p = 0.032).
  
  
  CONCLUSIONS
  MMP-9/ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.
authors.affiliation: Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan.|Department of Hospital Pharmacy, Abashiri Kosei General Hospital, Abashiri, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hiura
authors.affiliation: Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Department of Hospital Pharmacy, Engaru Kosei General Hospital, Engaru, Japan.
authors.forename: Chinami
authors.initials: C
authors.lastname: Suzuki
authors.affiliation: First Department of Internal Medicine, Obihiro Kosei General Hospital, Obihiro, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takamura
authors.affiliation: First Department of Internal Medicine, Obihiro Kosei General Hospital, Obihiro, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Hospital Pharmacy, Obihiro Kosei General Hospital, Obihiro, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komori
authors.affiliation: Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iwaki-Egawa
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D001772:Blood Cell Count; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010984:Platinum / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D010984:Platinum; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel
keywords: Absolute neutrophil count; VEGF; matrix metalloproteinase-9; progression-free survival; tumor reduction rate