title: Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer: a Prostate Cancer Clinical Trials Consortium trial.
abstract: BACKGROUND
  Treatment of high-risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy.
  
  
  METHODS
  Eligibility included any of the following: prostate-specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m(2) every 3 weeks for 6 cycles and bevacizumab 15 mg/m(2) every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI.
  
  
  RESULTS
  Forty-one patients were treated. Median age was 55 years (range, 40-66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty-eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%-45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%-38%) achieved a >50% post-treatment decline in PSA. Thirty-seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses.
  
  
  CONCLUSIONS
  Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials.
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ross
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Phil
authors.initials: P
authors.lastname: Febbo
authors.forename: Marc
authors.initials: M
authors.lastname: Barry
authors.forename: Jerome P
authors.initials: JP
authors.lastname: Richie
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Fennessy
authors.forename: Rupal S
authors.initials: RS
authors.lastname: Bhatt
authors.forename: Julia
authors.initials: J
authors.lastname: Hayes
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Clare M
authors.initials: CM
authors.lastname: Tempany
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Mary E
authors.initials: ME
authors.lastname: Taplin
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood*; D000077143:Docetaxel; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D060787:Neoplasm Grading; D009503:Neutropenia / Q000139:chemically induced; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D018570:Risk Assessment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D017430:Prostate-Specific Antigen