title: A phase II pharmacodynamic study of preoperative figitumumab in patients with localized prostate cancer.
abstract: OBJECTIVE
  Activation of the insulin-like growth factor 1 receptor (IGF-IR) is implicated in prostate cancer development and progression. This study evaluated biologic and clinical effects of figitumumab, a fully human monoclonal IGF-IR antibody, in patients with localized prostate cancer.
  
  
  METHODS
  Eligible patients received figitumumab 20 mg/kg intravenously every 3 weeks for 3 cycles followed by prostatectomy. The primary endpoint was IGF-IR expression inhibition as assessed by immunohistochemistry.
  
  
  RESULTS
  Sixteen patients were accrued. Median age was 63 years, median prostate-specific antigen (PSA) was 7.2 μg/L (range, 2.5-35), clinical stage was T1 in four patients and T2 in 12 patients, Gleason score ≤ 7 or >7 in 15 and one patients. Two patients received only 1 cycle (patient choice and grade III hyperglycemia). A PSA decline from baseline of ≥ 25% and ≥ 50% occurred in 15 (94%) and 5 (31%) of patients. Mean figitumumab concentration was 350.4 μg/mL (range, 26.3-492.8) in plasma and 51.3 μg/g (range, 27.4-79.6) in prostate tissue. Compared with pretreatment biopsies, IGF-IR expression decreased in the prostatectomy specimens in 14 of 16 patients. The mean IGF-IR immunohistochemistry visual score was 2.1 (SD = 0.6) in biopsy and 1.1 (SD = 0.5) in prostatectomy specimens (P < 0.0001). Androgen receptor expression was also decreased and there was a trend for a decrease in downstream IGF-IR signaling components.
  
  
  CONCLUSIONS
  Figitumumab is biologically active in prostate cancer. PSA declines in treatment-naive patients were observed, potentially mediated by IGF-IR effects on androgen receptor expression. These results support the clinical relevance of IGF-IR signaling in prostate cancer and justify further clinical trials.
authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada. kchi@bccancer.bc.ca
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: S Larry
authors.initials: SL
authors.lastname: Goldenberg
authors.forename: Alan
authors.initials: A
authors.lastname: So
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.forename: Anna
authors.initials: A
authors.lastname: Tinker
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D017526:Receptor, IGF Type 1; D017430:Prostate-Specific Antigen; C525021:figitumumab