title: Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer.
abstract: OBJECTIVE
  This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
  
  
  METHODS
  A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
  
  
  CONCLUSIONS
  Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Center for Breast Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Jungsil
authors.initials: J
authors.lastname: Ro
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea.
authors.forename: Hong Suk
authors.initials: HS
authors.lastname: Song
authors.affiliation: Department of Hematology and Oncology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seok Yun
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
authors.forename: Hee Sook
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D000078183:Oxindoles; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011758:Pyrroles; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D015850:Interleukin-6; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D005346:Fibroblast Growth Factors; D002097:C-Reactive Protein; C412603:orantinib
keywords: Angiogenesis; Biological markers; Breast neoplasms; Pharmacology; TSU-68