PMID- 22553344
OWN - NLM
STAT- MEDLINE
DCOM- 20121220
LR  - 20220317
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 18
IP  - 12
DP  - 2012 Jun 15
TI  - A phase II pharmacodynamic study of preoperative figitumumab in patients with 
      localized prostate cancer.
PG  - 3407-13
LID - 10.1158/1078-0432.CCR-12-0482 [doi]
AB  - PURPOSE: 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. EXPERIMENTAL DESIGN: 
      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 
      mug/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 mug/mL (range, 26.3-492.8) in plasma and 51.3 
      mug/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.
CI  - (c)2012 AACR.
FAU - Chi, Kim N
AU  - Chi KN
AD  - Vancouver Prostate Centre, Vancouver, British Columbia, Canada. 
      kchi@bccancer.bc.ca
FAU - Gleave, Martin E
AU  - Gleave ME
FAU - Fazli, Ladan
AU  - Fazli L
FAU - Goldenberg, S Larry
AU  - Goldenberg SL
FAU - So, Alan
AU  - So A
FAU - Kollmannsberger, Christian
AU  - Kollmannsberger C
FAU - Murray, Nevin
AU  - Murray N
FAU - Tinker, Anna
AU  - Tinker A
FAU - Pollak, Michael
AU  - Pollak M
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120502
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - VE267FC2UB (figitumumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal
MH  - Combined Modality Therapy
MH  - Disease Progression
MH  - Humans
MH  - Immunoglobulins, Intravenous/pharmacology/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prostate-Specific Antigen/blood
MH  - *Prostatectomy
MH  - Prostatic Neoplasms/*drug therapy/metabolism/pathology/surgery
MH  - *Receptor, IGF Type 1/antagonists & inhibitors/blood/immunology
EDAT- 2012/05/04 06:00
MHDA- 2012/12/21 06:00
CRDT- 2012/05/04 06:00
PHST- 2012/05/04 06:00 [entrez]
PHST- 2012/05/04 06:00 [pubmed]
PHST- 2012/12/21 06:00 [medline]
AID - 1078-0432.CCR-12-0482 [pii]
AID - 10.1158/1078-0432.CCR-12-0482 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2012 Jun 15;18(12):3407-13. doi: 10.1158/1078-0432.CCR-12-0482. 
      Epub 2012 May 2.