Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
Clin Cancer Res. 2012 Jun 15;18(12):3407-13. doi: 10.1158/1078-0432.CCR-12-0482. Epub 2012 May 2.
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.
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.
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.
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.
胰岛素样生长因子 1 受体（IGF-1R）的激活与前列腺癌的发生和发展有关。本研究评估了 figitumumab（一种完全人源化的 IGF-1R 单克隆抗体）在局限性前列腺癌患者中的生物学和临床效应。
符合条件的患者接受 figitumumab 20 mg/kg 静脉注射，每 3 周一次，共 3 个周期，随后行前列腺切除术。主要终点是通过免疫组织化学评估 IGF-1R 表达抑制。
共入组 16 例患者。中位年龄为 63 岁，中位前列腺特异性抗原（PSA）为 7.2 μg/L（范围 2.5-35），临床分期 4 例为 T1 期，12 例为 T2 期，Gleason 评分≤7 或>7 的分别为 15 例和 1 例。2 例患者仅接受了 1 个周期（患者选择和 3 级高血糖）。15 例（94%）和 5 例（31%）患者的 PSA 较基线下降≥25%和≥50%。血浆中 figitumumab 浓度的平均值为 350.4 μg/mL（范围 26.3-492.8），前列腺组织中为 51.3 μg/g（范围 27.4-79.6）。与预处理活检相比，16 例患者中有 14 例前列腺切除术标本中的 IGF-1R 表达降低。活检和前列腺切除术标本中 IGF-1R 免疫组化视觉评分的平均值分别为 2.1（SD=0.6）和 1.1（SD=0.5）（P<0.0001）。雄激素受体表达也降低，IGF-1R 信号下游成分也呈下降趋势。
figitumumab 在前列腺癌中具有生物学活性。在未接受治疗的患者中观察到 PSA 下降，可能是 IGF-1R 对雄激素受体表达的影响所致。这些结果支持 IGF-1R 信号在前列腺癌中的临床相关性，并证明了进一步临床试验的合理性。
