title: Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors.
abstract: OBJECTIVE
  VB-111 is an antiangiogenic agent consisting of a nonreplicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a Fas-chimera transgene in angiogenic endothelial cells. In a phase I dose-escalation study, pharmacokinetics, pharmacodynamics, safety, and efficacy of a single dose of VB-111 in patients with advanced solid tumors were evaluated.
  
  
  METHODS
  VB-111 was administered as a single i.v. infusion at escalating doses from 1 × 10(10) (cohort 1) to 1 × 10(13) (cohort 7) viral particles (VP) in successive cohorts. Assessments included pharmacokinetic and pharmacodynamic profiles, tumor response, and overall survival.
  
  
  RESULTS
  Thirty-three patients were enrolled. VB-111 was safe and well-tolerated; self-limited fever and chills were seen at doses above 3 × 10(11) VPs. Transgene expression was not detected in blood but was detected in an aspirate from a subcutaneous metastasis after treatment. One patient with papillary thyroid carcinoma had a partial response.
  
  
  CONCLUSIONS
  VB-111 was safe and well tolerated in patients with advanced metastatic cancer at a single administration of up to 1 × 10(13) VPs. Evidence of transgene expression in tumor tissue and tumor response was observed.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, Texas, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brenner
authors.forename: Yael C
authors.initials: YC
authors.lastname: Cohen
authors.forename: Eyal
authors.initials: E
authors.lastname: Breitbart
authors.forename: Livnat
authors.initials: L
authors.lastname: Bangio
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Ernest C
authors.initials: EC
authors.lastname: Borden
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000628:therapy*; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D042501:Angiogenic Proteins; D016207:Cytokines