An evaluation of bicalutamide in the treatment of prostate cancer

Prostate cancer is a major health problem in men, causing significant morbidity and mortality. Although traditionally considered a disease of old age, improved diagnostic techniques have resulted in earlier diagnosis and many men are now treated while still physically and sexually active. Current therapies for prostate cancer, which include medical or surgical castration, have a significant impact on many aspects of quality of life. The non-steroidal antiandrogen bicalutamide (Casodex?, AstraZeneca) has a favourable tolerability profile with demonstrated efficacy in several stages of prostate cancer and represents an alternative therapeutic strategy to castration. Mature survival data from men with previously untreated, locally-advanced disease reveal that bicalutamide monotherapy provides survival benefits that do not differ significantly from castration, while offering important advantages with respect to the maintenance of physical capacity and sexual interest. Recent data from a prospective randomised trial, the largest prostate cancer treatment study ever conducted, demonstrate that immediate therapy with bicalutamide (alone or as an adjuvant to therapy of curative intent) significantly reduces the risk of objective disease progression in patients with localised or locally-advanced prostate cancer. Antiandrogens are also used in combination with castration (combined androgen blockade) for advanced disease. Another large, randomised trial demonstrated that combined androgen blockade with bicalutamide is associated with a similar survival outcome to combined androgen blockade with flutamide and is better tolerated. The evidence reviewed demonstrates that bicalutamide currently has a favourable risk:benefit ratio in several stages of prostate cancer. The role of bicalutamide will be further defined by ongoing studies.     

An update on bicalutamide in the treatment of prostate cancer

In this update, bicalutamide (Casodex, Zeneca Pharmaceuticals) has been confirmed as an effective, well-tolerated and convenient non-steroidal anti-androgen for advanced prostate cancer. Preclinical and clinical studies have indicated its potential as monotherapy, with quality of life advantages compared with castration. A head-to-head comparison with flutamide, where both anti-androgens were used as part of combined androgen blockade, has suggested that the choice of components in this regimen can influence outcome, and has demonstrated that bicalutamide is better tolerated than flutamide. There is also preliminary evidence to support the potential use of bicalutamide in treatment of early-stage disease and tumours that are refractory to other non-steroidal anti-androgens.     

比卡鲁胺治疗前列腺癌的临床应用

比卡鲁胺是一种新型的非甾体抗雄激素药物,内分泌治疗是前列腺癌治疗的主要手段。本文就比卡鲁胺单药治疗前列腺癌、联合化疗治疗前列腺癌及联合放疗或去势手术治疗前列腺癌的临床疗效作一综述。     

Spotlight on bicalutamide 150mg in the treatment of locally advanced prostate cancer

Bicalutamide (Casodex) is a competitive androgen receptor antagonist that inactivates androgen-regulated prostate cell growth and function, leading to cell apoptosis and inhibition of prostate cancer growth. It is administered orally as a once-daily dose. In the EU and a number of other countries, bicalutamide 150 mg/day is approved in men with locally advanced nonmetastatic prostate cancer as immediate therapy either as an adjuvant to active treatment or as monotherapy as an alternative to surgical or medical castration.Combined analysis of the three trials that comprise the bicalutamide Early Prostate Cancer programme showed that bicalutamide administered in conjunction with standard care in men with locally advanced prostate cancer offers disease-free survival benefits over standard care alone and is generally well tolerated. Overall survival was improved to a greater extent in the subgroup of patients who received bicalutamide plus radiation therapy compared with radiation therapy alone. Men with localised prostate cancer do not benefit from the addition of bicalutamide to standard care. Combined analysis of two other studies in men with locally advanced prostate cancer show that bicalutamide monotherapy offers better tolerability and higher health-related quality-of-life scores for sexual interest and physical capacity compared with surgical or medical castration, while achieving disease-free and overall survival durations that were not significantly different. Thus, when treatment options are being evaluated, bicalutamide as adjuvant therapy or monotherapy should be considered as an alternative to other available hormonal therapies in men with locally advanced prostate cancer, especially in those who wish to maintain an active lifestyle.     

An evaluation of apalutamide for the treatment of prostate cancer

ABSTRACT

Introduction

Novel androgen signaling inhibitors are currently standard of care in the treatment of patients with prostate cancer. Second-generation androgen receptor antagonists have demonstrated efficacy in earlier disease settings, fulfilling an unmet need in the treatment of patients with advanced prostate cancer.     

比卡鲁胺与氟他胺治疗晚期去势抵抗性前列腺癌的临床比较

目的探讨比卡鲁胺与氟他胺治疗晚期去势抵抗性前列腺癌的疗效比较。方法分别以比卡鲁胺、氟他胺联合雄激素阻断治疗晚期前列腺癌,观察治疗前后的临床症状、血清PSA和血清睾酮不同时期的水平。结果比卡鲁胺组与氟他胺组服药后PSA值24、32、42月组间差异比较有统计学差异,临床表现改善比卡鲁胺组优于氟他胺组(P<0.05),两组间血清睾酮水平无显著差异。结论比卡鲁胺治疗晚期前列腺癌能明显控制前列腺癌疾病进展,改善尿路梗阻与骨痛等症状,与氟他胺相比,可减少去势抵抗性前列腺癌的发生。     

多西紫杉醇与比卡鲁胺治疗激素抵抗性前列腺癌的效果对比

目的观察多西紫杉醇及比卡鲁胺治疗激素抵抗性前列腺癌（HRPC）的效果。方法选取本院2007年1月～2013年12月收治的有完整资料的HRPC患者66例,将其随机分为观察组及对照组,每组各33例,观察组给予比卡鲁胺联合泼尼松治疗,对照组给予多西紫杉醇联合泼尼松治疗,比较两组患者的疗效以及不良反应。结果观察组治疗的有效率为66．7％,对照组为36．4％,观察组的有效率明显高于对照组,差异有统计学意义（X2=6．06,P〈0．05）。观察组的不良反应发生率为36．4％,对照组为69．7％,组间差异有统计学意义（X2=7．36,P〈0．05）。结论比卡鲁胺联合波尼松治疗HRPC患者的效果优于多西紫杉醇,且不良反应较少。     

近距离放疗联合比卡鲁胺150mg在前列腺癌治疗中的应用

目的 探讨近距离放疗联合比卡鲁胺150 mg单药治疗前列腺癌的可行性.方法 将符合入选标准的71例前列腺癌患者按随机数字表分为单药组(34例)和联合药物组(37例).接受近距离放疗后,单药组采用比卡鲁胺150 mg单药内分泌治疗;联合药物组接受戈舍瑞林3.6 mg+比卡鲁胺50 mg内分泌治疗.分别观察治疗前后的前列腺特异抗原(PSA)变化情况,第一阶段用药时间,严密记录治疗过程中的不良事件,并进行安全性评价.结果 单药组有2例、联合药物组有1例在治疗1年后血清PSA不能下降到术前的50％予以剔除.2组患者在接受近距离放疗联合药物治疗1个月后,PSA值均出现了“断崖式”的下降.在随后的治疗中,联合药物组和单药组不良反应发生率差异无统计学意义[(41.7％(15/36)比31.3％(10/32),P=0.37].PSA抑制率二者差异有统计学意义[(96±24)％比(98±24)％,P＜0.01),但对于低危患者,二者差异无统计学意义[(98±24)％比(100±25)％,P＞0.05).联合药物组用药时间短于单药组[(8.1±2.0)个月比(9.5±2.5)个月,P＜0.01],但对于低危患者,二者之间差异无统计学意义(P＞0.05).结论 前列腺癌的近距离放疗联合戈舍瑞林3.6 mg+比卡鲁胺50 mg双药内分泌治疗效果较好,而对于低危患者,采用比卡鲁胺150 mg单药联合近距离放疗的方案,亦能达到同样效果.     

比卡鲁胺胶囊对前列腺癌术后患者恢复效果的影响

目的 观察比卡鲁胺胶囊对前列腺癌术后患者恢复效果的影响.方法 选取2016年4月-2019年12月新疆生产建设兵团第十三师红星医院收治的前列腺癌患者80例,根据随机数字表法分为观察组和对照组,各40例.对照组患者接受前列腺癌手术去势治疗,观察组在对照组治疗基础上加用比卡鲁胺胶囊治疗.比较2组患者近期疗效,治疗前后前列腺...     

比卡鲁胺联合塞来昔布对前列腺癌细胞LNCaP增殖的影响

目的观察比卡鲁胺联合塞来昔布对前列腺癌细胞LNCaP增殖的影响并探讨其可能的作用机制。方法培养前列腺癌LNCaP细胞,采用MTT法测定细胞生长的抑制情况,化学发光法检测细胞培养液中总前列腺特异抗原(PSA)的浓度,流式细胞仪检测各组细胞的凋亡率,Western Blot检测各组细胞Caspase 3和Caspase 8蛋白的表达情况。结果 MTT检测结果显示,对照组在24,48和72 h的细胞生长抑制率均为0。比卡鲁胺组、塞来昔布组和联合组在24,48和72 h的生长抑制率均明显较高(P<0.05)。对组间细胞的生长抑制率联合组显著优于单一组(P<0.05)。化学发光法检测结果显示,与对照组相比,比卡鲁胺组、塞来昔布组以及联合组PSA浓度明显降低,其中联合组对PSA的抑制程度明显优于比卡鲁胺组和塞来昔布组(P<0.05)。流式细胞仪检测结果显示,对照组在24,48和72 h的细胞凋亡率均低于比卡鲁胺组、塞来昔布组和联合组在24,48和72 h的生长抑制率。组间细胞的生长抑制率联合组显著优于比卡鲁胺组和塞来昔布组(P<0.05)。Western Blot结果提示,与对照组相比,给药组Caspase 3和Caspase 8蛋白的表达水平均显著升高,且联合组明显高于比卡鲁胺组和塞来昔布组(P<0.05)。结论比卡鲁胺联合塞来昔布能有效抑制前列腺癌细胞LNCaP的增殖,其机制可能与促进相关蛋白Caspase 3和Caspase 8凋亡进而促进肿瘤细胞的凋亡有关。     

An evaluation of the pharmacokinetics and pharmacodynamics of the histrelin implant for the palliative treatment of prostate cancer

Seventeen patients with advanced prostate cancer were studied to evaluate the pharmacokinetics and pharmacodynamics of a hydrogel implant designed to deliver histrelin at a constant rate (50 microg/d) for 1 year. Serum histrelin levels were collected during the 52-week implantation period and after a second implant. Testosterone suppression was the primary pharmacodynamic endpoint, with treatment success defined as serum testosterone less than 50 ng/dL. The histrelin subdermal implant delivered constant histrelin levels, with mean serum histrelin of approximately 0.265 ng/mL over 52 weeks. At the end of 52 weeks, mean histrelin concentrations were 0.128 +/- 0.0652 ng/mL. Patients achieved chemical castration (testosterone less than 50 ng/mL) by week 4. In patients who had the first implant removed and received a new implant at the end of the first 52 weeks, testosterone suppression was not interrupted. The hydrogel implant provided consistent delivery of histrelin over 1 year and effectively suppressed testosterone in men with prostate cancer.     

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer

Introduction: To evaluate the safety profile characteristics of abiraterone acetate (AA) in the treatment of metastatic prostate cancer (mPCa).

Areas covered: In this literature review the authors evaluate safety data from phase III trials investigating the combination of abiraterone acetate plus prednisone (AAP) in patients with metastatic prostate cancer. In particular, the aim was to clarify its toxicity profile, long-term exposure impact, and the correlation with general health-related quality of life (HRQoL).

Expert opinion: Based on the studies reviewed, it appears that abiraterone acetate has favourable outcomes, is effective and well tolerated, mostly in asymptomatic or slightly symptomatic patients, and has recognised toxicity profile characteristics. Incidence of adverse events (AEs), such as mineralocorticoid- and corticosteroid-releated AEs, and hepatotoxicity is well known and widely described. Understanding the toxicity profile of AA could assist decision-making in clinical practice.     

Biological evaluation of RGDfK-gold nanorod conjugates for prostate cancer treatment

Selective delivery of gold nanorods (GNRs) to sites of prostate tumor angiogenesis is potentially advantageous for localized photothermal therapy. Here, we report the cellular uptake and biodistribution of GNRs surface functionalized with the cyclic RGDfK peptide. The GNRs were synthesized to have a surface plasmon resonance (SPR) peak at 800?nm and grafted with a thiolated poly(ethylene glycol) (PEG) corona with or without RGDfK. The binding and uptake of the targeted (RGDfK) and untargeted GNRs were evaluated in DU145 prostate cancer and human umbilical vein endothelial cells (HUVEC) by high-resolution dark field microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). The biodistribution of both GNRs was then evaluated in prostate tumor bearing mice. Targeting of the RGDfK surface-modified GNRs was confirmed in vitro due to selective binding and uptake by endothelial cells. Tumor targeting was not observed in vivo, however, due to fast clearance of the RGDfK-GNRs from the blood. Further modifications of the nanoparticle’s surface properties are needed to enhance localization of the targetable system in sites of tumor angiogenesis.     

曲普瑞林治疗中国局部晚期或转移性前列腺癌的药物经济学评价

目的：对曲普瑞林治疗局部晚期或转移性前列腺癌（PCa）进行药物经济学评价。方法：从卫生体系角度出发,采用Markov模型,对比曲普瑞林相较于其他促性腺激素释放激素激动剂（luteinizing hormone releasing hormone agonists,LHRHa）的经济性。结果：曲普瑞林3M剂型相较戈舍瑞林和亮丙瑞林3M剂型的增量成本效果比（ICER）分别为41 950元/QALY和6 515元/QALY,均远低于2020年中国的1倍人均GDP。相较于戈舍瑞林和亮丙瑞林3M剂型,曲普瑞林6M剂型为患者增加的QALYs分别为0.14和0.11,同时总成本均降低。结论：与目前已上市的LHRHa相比,曲普瑞林治疗局部晚期或转移性PCa具有成本效果优势。     

Signaling inhibitors in the treatment of prostate cancer

Inhibiting androgen receptor (AR) activation through medical or surgicalcastration and blockade of AR-androgen binding is the cornerstone oftreatment for advanced prostate cancer. However, in most cases tumorgrowth eventually becomes androgen independent. Alternative mechanisms ofAR activation, some of which involve growth factor receptor signaling,have been demonstrated in prostate cancer models, and it is likely that anumber of autocrine and paracrine growth factor ligand-receptorinteractions such as those of epidermal growth factors, fibroblast growthfactors, and insulin-like growth factors contribute to the androgenindependent phenotype by promoting cell proliferation and survival.Blocking activation through growth factor receptors and upstream signalingproteins has emerged as a credible approach to cancer treatment.Successful application of this approach in prostate cancer using a growingarray of small molecule kinase inhibitors, antibodies, and antisenseoligonucleotides will be greatly accelerated by elucidation of the keysignaling pathways that maintain the androgen independent phenotype.     

Angiogenesis inhibitors in the treatment of prostate cancer

Importance of the field: Prostate carcinoma is the most common non-cutaneous malignancy in U.S. men. The efficacy of docetaxel and prednisone in metastatic castrate-resistant prostate cancer (mCRPC) has been shown to improve overall survival; however, its effect is not durable, highlighting the need for new therapies.

Areas covered in this review: We will review the development of some of the leading compounds with direct and indirect antiangiogenic activity in prostate cancer including antibodies to VEGF and its receptors, small-molecule inhibitors of downstream signaling, immunomodulatory drugs with antiangiogenic activity, and compounds thought to directly inhibit or destroy vascular endothelial cells.

What the reader will gain: The reader will gain a basic understanding of the role of angiogenesis in prostate cancer growth and metastasis. Current and potential targets of angiogenesis and their corresponding drugs under development for prostate cancer are discussed.

Take home message: There are now multiple early-phase clinical trials of antiangiogenic agents alone or in combination in prostate cancer. Several of these agents are now in Phase III development. Combined therapy with two antiangiogenic compounds may improve the activity of either compound alone. Multiple targets in the angiogenesis pathway continue to be elucidated and should remain an active area of investigation for the treatment of prostate cancer.     

Current concepts in the treatment of prostate cancer

Carcinoma of the prostate is one of the most common cancers in men over 50 years of age and is the second leading cause of cancer death in men over 75. As a general rule, symptoms usually are not apparent until the tumor is far advanced. Between 80 to 90 percent of patients have metastatic disease at the time of presentation and are not curable by surgery. Endocrine manipulation remains the most effective and commonly used treatment for metastatic carcinoma of the prostate.     

前列腺癌治疗研究进展

前列腺癌在男性的致死性癌症中居第二位。由于前列腺癌的绝对发病率会随着年龄的增大呈线性增加,老年人患病的几率非常大。近年来,社会老龄化现象又在日趋严重,因此,庞大且持续增长的患者群使得前列腺癌治疗领域颇具开发潜力。尽管有着如此巨大的市场需求,但由于前列腺是一个非常特殊的人体组织,常规的抗癌化疗药物很难渗入其内部并发挥疗效,