Effect of the somatostatin analog octreotide acetate on circulating insulin-like growth factor-1 and related peptides in patients with non-metastatic castration-resistant prostate cancer: Results of a phase II study
Effect of the somatostatin analog octreotide acetate on circulating insulin-like growth factor-1 and related peptides in patients with non-metastatic castration-resistant prostate cancer: Results of a phase II study
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DOI：
10.1016/j.urolonc.2010.06.014
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发表时间：
2012-07-01
影响因子：
2.7
通讯作者：
Ryan, Charles J.
中科院分区：
文献类型：
--
作者：
Friedlander, Terence W.;Weinberg, Vivian K.;Ryan, Charles J.
背景资料：胰岛素样生长因子（IGF）介导的信号转导与许多肿瘤类型（包括前列腺癌）的生长有关，并且假设降低去势抵抗性前列腺癌（CRPC）男性的循环IGF水平将减缓肿瘤生长。在这项研究中，贮库型醋酸奥曲肽的疗效进行了前瞻性评估CRPC.Methods患者：符合条件的患者进行性非转移性CRPC。醋酸奥曲肽30 mg肌肉注射，每28天一次。PSA，IGF-1，IGF-2，IGF结合蛋白-1（IGFBP-1），IGFBP-3的变化进行了评估，随着时间的推移。结果：累积提前停止后，预先计划的中期分析显示，没有前列腺特异性抗原（PSA）下降后3个周期的治疗中的第一个13例患者入组。中位基线PSA和IGF-1测量值分别为36.2 ng/ml和162.6 ng/ml，中位治疗时间为13周。7例患者发生放射学进展，5例患者发生仅PSA进展，1例患者因3级药物相互作用退出研究。治疗3个周期后，IGF-1显著下降，中位数为-34.5%（P = 0.01），IGFBP-1显著升高，中位数为76.3%（P = 0.046）。IGF-2和IGFBP-3没有显着改变，从baseline.Conclusions：醋酸奥曲肽显着降低IGF-1和提高IGFBP-1水平的非转移性CRPC患者，但不会导致PSA的持续下降。虽然奥曲肽单药治疗可能没有必要，但将其纳入直接靶向肿瘤细胞上IGF-1受体的联合治疗方案中可能是有意义的。(c)2012 Elsevier Inc. All rights reserved.
Background: Insulin-like growth factor (IGF) mediated signaling has been implicated in the growth of many tumor types including prostate cancer, and it is hypothesized that lowering circulating IGF levels in men with castration resistant prostate cancer (CRPC) will slow tumor growth. In this study, the efficacy of depot octreotide acetate was prospectively evaluated in patients with CRPC.Methods: Eligible patients had progressive non-metastatic CRPC. Octreotide acetate 30 mg was administered intramuscularly every 28 days. Changes in PSA, IGF-1, IGF-2, IGF binding protein-1 (IGFBP-1), and IGFBP-3 were evaluated over time.Results: Accrual was stopped early after a pre-planned interim analysis showed no prostate specific antigen (PSA) declines after 3 cycles of treatment among the first 13 patients enrolled. Median baseline PSA and IGF-1 measurements were 36.2 ng/ml and 162.6 ng/ml, respectively, and median time on treatment was 13 weeks. Radiographic progression occurred in 7 patients, PSA-only progression occurred in 5 patients, and 1 patient was taken off the study due to a grade 3 drug interaction. After 3 cycles of treatment IGF-1 significantly declined with a median -34.5% (P = 0.01) and IGFBP-1 significantly increased with a median 76.3% (P = 0.046). IGF-2 and IGFBP-3 were not significantly changed from baseline.Conclusions: Octreotide acetate significantly lowers IGF-1 and raises IGFBP-1 levels in patients with non-metastatic CRPC, but does not result in sustained declines in PSA. While treatment with single-agent octreotide may not be warranted, its inclusion in combination regimens directly targeting the IGF-1 receptor on tumor cells may be of interest. (c) 2012 Elsevier Inc. All rights reserved.