A phase II pharmacodynamic study of preoperative figitumumab in patients with localized prostate cancer.

Abstract

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 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: Kim N Chi, Martin E Gleave, Ladan Fazli, S Larry Goldenberg, Alan So, Christian Kollmannsberger, Nevin Murray, Anna Tinker, Michael Pollak
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 12 Pg. 3407-13 (Jun 15 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22553344 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulins, Intravenous
• Receptor, IGF Type 1
• Prostate-Specific Antigen
• figitumumab

Topics

• Aged
• Antibodies, Monoclonal
• Combined Modality Therapy
• Disease Progression
• Humans
• Immunoglobulins, Intravenous (pharmacology, therapeutic use)
• Male
• Middle Aged
• Neoplasm Staging
• Prostate-Specific Antigen (blood)
• Prostatectomy
• Prostatic Neoplasms (drug therapy, metabolism, pathology, surgery)
• Receptor, IGF Type 1 (antagonists & inhibitors, blood, immunology)