科研之友
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摘要
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 mu g/L (range, 2.5-35), clinical stage was T1 in four patients and T2 in 12 patients, Gleason score <= 7or >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 mu g/mL (range, 26.3-492.8) in plasma and 51.3 mu g/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. Clin Cancer Res; 18(12); 3407-13.
- 出版日期2012-6-15
