title: Phase II study of Aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a California Cancer Consortium Trial.
abstract: OBJECTIVE
  To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer.
  
  
  METHODS
  Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19.
  
  
  RESULTS
  A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred.
  
  
  CONCLUSIONS
  Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.
authors.affiliation: City of Hope Cancer Ctr, Duarte, CA, USA. ptwardowski@coh.org
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Twardowski
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Christopher
authors.initials: C
authors.lastname: Ruel
authors.forename: Gurkamal
authors.initials: G
authors.lastname: Chatta
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Heath
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D017211:Treatment Failure; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor