title: An open-label, phase 2 trial of RPI.4610 (Angiozyme) in the treatment of metastatic breast cancer.
abstract: BACKGROUND
  Serum and plasma levels of vascular endothelial growth factor (VEGF) correlate with prognosis in patients with metastatic breast cancer (MBC). VEGF binds to 2 receptors on endothelial cells, VEGFR-1 and VEGFR-2. RPI.4610 (Angiozyme0) is an antiangiogenic ribozyme targeting the VEGFR-1 mRNA. Preclinical and phase 1 studies suggested that RPI.4610 is a well-tolerated agent with clinical activity in solid tumors. The authors' trial evaluated the efficacy of RPI.4610 in the treatment of patients with progressive MBC.
  
  
  METHODS
  This phase 2, multicenter, single-arm study was designed to assess the objective response rate of RPI.4610 in patients with MBC who had experienced disease progression with at least 1 course of chemotherapy for MBC. Patients received daily subcutaneous injections of RPI.4610 100 mg/m(2) for 12 weeks.
  
  
  RESULTS
  Most patients (93%) had received at least 2 lines of chemotherapy previously; 69% of patients had received at least 3 lines of chemotherapy. Median follow-up was 2.76 months (range, 0.89-36.6 months). No partial responses nor complete responses were found. Median progression-free survival was 1.41 months (95% confidence interval [CI], 1.35-1.45). The median overall survival from start of treatment was 11.89 months (95% CI, 4.11-23.66). Treatment-related adverse events (AEs) were primarily grade 1 to 2 in intensity. Most common AEs were: injection site reactions, abdominal pain, anorexia, chromaturia, constipation, dyspnea, fatigue, headache, pain at the injection site, nausea, vomiting, and fever.
  
  
  CONCLUSIONS
  Although RPI.4610 demonstrated a well-tolerated safety profile, its lack of clinical efficacy precludes this drug from further development.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. pmorrow@mdanderson.org
authors.forename: Phuong Khanh
authors.initials: PK
authors.lastname: Morrow
authors.forename: Rashmi K
authors.initials: RK
authors.lastname: Murthy
authors.forename: Joe D
authors.initials: JD
authors.lastname: Ensor
authors.forename: Gilad S
authors.initials: GS
authors.lastname: Gordon
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Elias
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: David E
authors.initials: DE
authors.lastname: Weng
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D016337:RNA, Catalytic / Q000009:adverse effects / Q000627:therapeutic use*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; C121301:Angiozyme; D016337:RNA, Catalytic; D040281:Vascular Endothelial Growth Factor Receptor-1