一种用于局部前列腺癌的雄激素拮抗剂 2-羟基氟他胺的前列腺内控释制剂。

An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer.

机构信息

Department of Urology, Tampere University Hospital and University of Tampere (TLT), Tampere, Finland; Department of Urology, Helsinki University Hospital (KT), Helsinki, Finland; Department of Urology, Päijät-Häme Central Hospital (TI), Lahti, Finland; Department of Urology, Uppsala University Hospital (MH, SL), Uppsala, Sweden; Radiology, Department of Surgical Sciences (JW, CvB, CW), Uppsala University, Uppsala, Sweden; Department of Pharmacy (HL), Uppsala University, Uppsala, Sweden; Department of Immunology Genetics and Pathology (AT), Uppsala University, Uppsala, Sweden; LIDDS AB (NA, CGG), Uppsala, Sweden; Department of Oncology, University of Örebro (BL), Örebro, Sweden.

出版信息

J Urol. 2017 Dec;198(6):1333-1339. doi: 10.1016/j.juro.2017.07.072. Epub 2017 Jul 20.

DOI:10.1016/j.juro.2017.07.072

PMID:28736321

Abstract

PURPOSE

We investigated the tolerability, safety and antitumor effects of a novel intraprostatic depot formulation of antiandrogen 2-hydroxyflutamide (in NanoZolid®) in men with localized prostate cancer.

MATERIALS AND METHODS

Two clinical trials, LPC-002 and LPC-003, were performed in a total of 47 men. The formulation was injected transrectally into the prostate under ultrasound guidance. In LPC-002 the effects on prostate specific antigen and prostate volume were measured for 6 months in 24 patients. In LPC-003 antitumor effects were evaluated by histopathology and magnetic resonance imaging including spectroscopy during 6 or 8 weeks in 23 patients. In each study testosterone and 2-hydroxyflutamide in plasma were measured as well as quality of life parameters.

RESULTS

In LPC-002 (mean dose 690 mg) a reduction was observed in prostate specific antigen and prostate volume. Average nadir prostate specific antigen and prostate volume were 24.9% and 14.0% below baseline, respectively. When increasing the dose in LPC-003 to 920 and 1,740 mg, average prostate specific antigen decreased 16% and 23% after 6 and 8 weeks, respectively. Magnetic resonance imaging and magnetic resonance spectroscopy showed morphological changes and a global reduction in metabolite concentrations following treatment, indicating an antitumor response. Injections did not result in hormone related side effects. Three serious adverse events were reported and all resolved with oral antibiotic treatment.

CONCLUSIONS

Intraprostatic injections of 2-hydroxyflutamide depot formulations showed antitumor effects, and proved to be safe and tolerable. However, for better anticancer effects higher doses and better dose distribution are suggested.

摘要

目的

我们研究了将新型抗雄激素 2-羟基氟他胺（NanoZolid®）的前列腺内储库制剂用于局部前列腺癌患者的耐受性、安全性和抗肿瘤作用。

材料和方法

共对 47 名男性进行了两项临床试验（LPC-002 和 LPC-003）。制剂在超声引导下经直肠注射入前列腺。在 LPC-002 中，24 名患者接受了 6 个月的前列腺特异性抗原和前列腺体积的影响评估。在 LPC-003 中，23 名患者在 6 或 8 周内通过组织病理学和磁共振成像（包括磁共振波谱）评估抗肿瘤作用。在每项研究中，均测量了血浆中的睾酮和 2-羟基氟他胺以及生活质量参数。

结果

在 LPC-002（平均剂量 690mg）中，前列腺特异性抗原和前列腺体积均降低。平均 PSA 最低值和前列腺体积分别比基线低 24.9%和 14.0%。当 LPC-003 增加剂量至 920 和 1740mg 时，6 和 8 周后 PSA 分别降低 16%和 23%。磁共振成像和磁共振波谱显示治疗后形态学改变和代谢物浓度的整体降低，表明存在抗肿瘤反应。注射不会导致与激素相关的副作用。报告了 3 例严重不良事件，所有事件均经口服抗生素治疗后得到解决。