title: A randomized Phase II trial of the tumor vascular disrupting agent CA4P (fosbretabulin tromethamine) with carboplatin, paclitaxel, and bevacizumab in advanced nonsquamous non-small-cell lung cancer.
abstract: BACKGROUND
  Combretastatin A4-phosphate, fosbretabulin tromethamine (CA4P) is a vascular disrupting agent that targets tumor vasculature. This study evaluated the safety of CA4P when combined with carboplatin, paclitaxel, and bevacizumab in chemotherapy-naïve subjects with advanced nonsquamous, non-small-cell lung cancer.
  
  
  METHODS
  Adult subjects with confirmed American Joint Committee on Cancer six stage IIIB/IV non-small-cell lung cancer and an Eastern Cooperative Oncology Group performance score of 0 or 1 were randomized to receive six cycles (treatment phase) of paclitaxel (200 mg/m2), carboplatin (area under the concentration versus time curve 6), and bevacizumab (15 mg/kg) on day 1 and repeated every 21 days, or this regimen plus CA4P (60 mg/m2) on days 7, 14, and 21 of each cycle. Subjects could then receive additional maintenance treatment (excluding carboplatin and paclitaxel) for up to 1 year.
  
  
  RESULTS
  Sixty-three subjects were randomized, 31 to control and 32 to CA4P, and 19 (61.3%) and 17 (53.1%), respectively, completed the treatment phase. Exposure to study treatment and dose modifications were comparable between the randomized groups. The overall incidence of treatment-emergent adverse events was similar between groups, with increased neutropenia, leukopenia, and hypertension in the CA4P group. Deaths, serious adverse events, and early discontinuations from treatment were comparable between the randomized treatment groups. The overall tumor response rate with CA4P was 50% versus 32% in controls. Overall and progression-free survival rates were comparable between the groups.
  
  
  CONCLUSIONS
  CA4P plus carboplatin, paclitaxel, and bevacizumab appears to be a tolerable regimen with an acceptable toxicity profile in subjects with advanced non-small-cell lung cancer.
authors.affiliation: Department of Medicine; Department of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.affiliation: San Juan Oncology Associates, Farmington, NM.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Neidhart
authors.affiliation: Gabrail Cancer Center, Canton, OH.
authors.forename: Nashat Y
authors.initials: NY
authors.lastname: Gabrail
authors.affiliation: Northwest Medical Specialties, Tacoma, WA.
authors.forename: Moacyr R
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Global Product Development and Immuno-Oncology, PPD, Wilmington, NC, USA.
authors.forename: Jai
authors.initials: J
authors.lastname: Balkissoon
authors.affiliation: Department of Medicine; Department of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
keywords: CA4P; NSCLC; bevacizumab; carboplatin; paclitaxel