前列腺癌去势治疗与骨质疏松

性激素在骨生成和维持骨量方面起重要作用。前列腺癌患者行手术或药物去势治疗后,随着体内睾酮及雌二醇的急剧下降,患者会出现骨矿物质密度(Bone Mineral Density,BMD)降低,骨质疏松的发病率增加,甚至会出现骨折。现对前列腺癌去势治疗与骨质疏松的关系、去势患者骨质疏松的管理以及治疗药物的研究现状综述如下。     

去势抵抗性前列腺癌的治疗策略

内分泌治疗是目前晚期前列腺癌的主要治疗方法,但大多数患者经过14～30个月的治疗后均逐渐发展为去势抵抗性前列腺癌（CRPC）,其中位生存期小于20个月。相关生物靶向治疗研究较为深入,多西他赛联合泼尼松方案已成为CRPC治疗的一线化疗方案,唑来膦酸盐能明显减少骨相关事件的发生率。然而,CRPC治疗策略制定仍是目前临床的一个难题,本文结合文献报道综述CRPC的治疗策略。     

去势抵抗性前列腺癌的治疗

去势抵抗性前列腺癌（Castrate-resistant prostate cancer,CRPC）指经过初次持续雄激素剥夺治疗后疾病依然进展的前列腺癌,是晚期前列腺癌病情发展的重要阶段。CRPC患者根据是否存在转移病灶、既往接受治疗以及体力状况等可进一步分类,恰当的药物治疗可使患者获益。本文从诊断、病因、分类、药物选择4个角度对CRPC的治疗进行综述,旨在为临床药师的工作实践提供参考。     

非转移去势抵抗性前列腺癌治疗新药——apalutamide

Apalutamide是一种口服的雄激素受体抑制剂,美国食品药品监督管理局批准其用于治疗非转移去势抵抗性前列腺癌患者。Apalutamide常见的不良反应包括皮疹、腹泻、疲劳、恶心、呕吐、高血压、血尿和骨折等。本文对apalutamide的药理作用、药物代谢动力学、临床评价、安全性、用法用量及药物相互作用等进行综述,旨在为临床用药提供参考。     

脂质代谢在去势抵抗性前列腺癌中的研究进展

在泌尿系统中,前列腺癌(PCa)是男性最常见的恶性肿瘤,其发病率逐年上升,并逐渐成为威胁全球老年男性生存质量的重要因素.目前包括手术和药物去势治疗在内的雄激素剥夺治疗可有效缓解PCa进程,是所有阶段复发性PCa的标准治疗手段,但最终都不可避免的发展为恶性程度更高的去势抵抗性前列腺癌(CRPC).近年来,脂代谢重编程在肿...     

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。     

经尿道前列腺电切术联合内分泌去势疗法治疗晚期前列腺癌的临床疗效

目的 研究经尿道前列腺电切术联合内分泌去势疗法治疗晚期前列腺癌的临床效果。方法 从2017年1月11日至2019年1月11日,收集郑州大学第二附属医院收入治疗的晚期前列腺癌患者中,选取114例作为此次研究对象,根据治疗方式不同分为对照组和观察组,将内分泌去势疗法患者设为对照组(57例),将经尿道前列腺电切术联合内分泌去势疗法设为观察组(57例),观察对比两组患者生活质量、实验室各项指标、治疗总有效率和三年的生存率。结果 治疗前,两组生活质量相比差异无统计学意义(P>0.05),治疗后,两组生活质量均有改善,且对比提示观察组优于对照组,P<0.05。治疗前,两组实验室各项指标相比差异无统计学意义(P>0.05),治疗后,观察组前列腺特异性抗原(PSA)和血管内皮生长因子(VEGF)的水平较对照组低,最大的尿流率较对照组高,残余尿量较对照组少,P<0.05。观察组治疗总有效率为96.49%,与对照组的84.21%相比明显增高,对比差异有统计学意义(P<0.05)。观察组1年生存率100.00%,两年生存率91.23%,三年生存率77.19%,均较对照组的87....     

去势抵抗性前列腺癌分子信号通路的研究进展

在美国前列腺癌(PCa)是男性最常见的非皮肤性癌症以及癌症相关死亡的第二号杀手。雄激素与雄激素受体是前列腺癌的关键效应器,因此,雄激素剥夺治疗(ADT)是前列腺癌患者的一线治疗方法,并且效果良好,但是前列腺肿瘤最终复发并进展为去势抵抗性前列腺癌(CRPC)这一致命性形式。研究雄激素受体与去势抵抗性前列腺癌发生发展的关系及其可能的分子机制,可以为其临床诊断、治疗以及进一步的研究提供科学依据。     

去势抵抗性前列腺癌治疗新药卡巴他赛

对于多西他赛治疗失败的转移性去势抵抗性前列腺癌（CRPC）患者,卡巴他赛能延长患者生存时间并改善患者症状。本文综述卡巴他赛作为转移性CRPC患者二线治疗药物的近期研究进展。     

Management of the side effects of androgen deprivation therapy in men with prostate cancer

Background: Androgen deprivation therapy is the foundation of the medical management of prostate cancer. Androgen deprivation therapy offers improved efficacy when used with local therapy such as external beam radiation therapy and substantial palliation in the metastatic setting. Objective: The adverse events of androgen deprivation therapy include hot flashes, decreased bone mineral density, metabolic changes and gynecomastia. Each of these is described as well as their individual management. Method: The medical literature pertaining to androgen deprivation therapy and its adverse events was reviewed with pertinent publications highlighted. Results: Despite the long history of androgen deprivation therapy use in prostate cancer, ongoing work continues to identify and define the adverse events better. For each complication and particularly with regard to metabolic syndrome, recent efforts continue to characterize the problem and its rational management.     

Pharmacotherapy for biochemical recurrences after therapy for localised prostate cancer

Prostate-specific antigen (PSA) has revolutionised screening for and monitoring of prostate cancer (CaP) [1]. Currently, most men failing potentially curative CaP therapies develop biochemical evidence of recurrent disease (defined by detectable PSA levels) long before the onset of clinical symptoms [1]. Androgen deprivation therapy (ADT) remains the gold standard for the treatment of metastatic CaP. Conventional ADT is orchiectomy or luteinising hormone-releasing hormone agonists. ADT is most commonly associated with side effects such as erectile dysfunction, decreased libido, gynecomastia and osteoporosis. Intermittent ADT or oral anti-androgens may limit the side effects associated with ADT while retaining efficacy. Although widely studied, the optimal timing to begin ADT remains an important and unanswered question. Future advances in gene therapy and immunotherapy hold the greatest promise to provide effective treatments against recurrent CaP while minimising morbidity.     

国产亮丙瑞林与手术去势治疗前列腺癌的疗效比较

目的：比较晚期前列腺癌患者分别采用国产亮丙瑞林药物去势与手术去势治疗的疗效和安全性。方法：60例患者随机采用国产亮丙瑞林药物去势或手术去势,并联合比卡鲁胺行全雄激素阻断,观察两种治疗方法的疗效及不良反应。结果：药物去势组与手术去势组的有效率分别为86.6%和83.3%（P〉0.05）,90%药物去势和93%手术去势患者的血清睾酮水平经6个月治疗后维持在去势水平。两组治疗相关不良反应主要表现为潮热、乳房胀痛、疲劳等,两组无统计学差异,但注射部位疼痛为药物去势所特有。结论：国产亮丙瑞林药物去势与手术去势相比,短期疗效确切,不良反应小,能改善患者的生活质量。     

Pharmacotherapy for prostate cancer,with emphasis on hormonal treatments

For more than half a century, hormonal therapy has been one of the cornerstones of prostate cancer therapy. However, the position and timing of androgen deprivation therapy is continuously challenged. Nowadays, it is often combined with other types of treatment in a multi-modal approach, especially with radiation therapy. Besides the well-known luteinising hormone-releasing hormone agonists, several developments have been introduced (e.g., luteinising hormone-releasing hormone antagonists or improved depot formulations achieving a better pharmacokinetic slope and lower testosterone levels). Research developments include a better understanding of the different gonadotropin-releasing hormone isoforms, the ligand-independent transformation of the androgen receptor and androgen receptor overexpression in hormone-insensitive disease. Prostate cancer, previously thought to be chemotherapy insensitive, is now treated at the metastatic stage by taxane-based chemotherapies. The combination of hormonal therapy and chemotherapy is currently studied at various stages of the disease, as early as localised or locally advanced prostate cancer. It is very likely that, in the future, pharmacological treatment for prostate cancer will include combination therapies rather than monotherapies. The authors suggest an in-depth re-evaluation of the place of androgen deprivation therapy in prostate cancer.     

Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer

Introduction: Hormone sensitive advanced prostate cancer (PCa) is an incurable disease that is treated with a variety of hormonal therapies targeting the androgen/androgen receptor signaling axis. For decades androgen deprivation therapy (ADT) by surgical or chemical castration is the gold standard for the treatment of advanced PCa.

Areas covered: This review discusses the pharmacological features of Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonists/analog and the most commonly used drug in ADT.

Expert opinion: Although Leuprolide has been on the market for more than 30 years it is still the leading option for ADT and serves as a basis for most multimodal therapy concepts. The fact that with the onset of castration-resistance in late stage metastatic disease, a prolongation of ADT in combination with a second line hormonal manipulation is recommended supports the importance of the compound for daily clinical practice.     

Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer

Introduction: Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing hormone-releasing hormone (LHRH) agonist, and more recently, gonadotropin releasing hormone (GnRH) antagonist therapy. Our understanding of the mechanisms and adverse effects of ADT has increased substantially, including the class-specific adverse effects of ADT.

Areas covered: This review will summarize the pharmacodynamic and pharmacokinetic properties of the GnRH antagonist degarelix and its role in the management of advanced prostate cancer, the clinical evidence supporting its regulatory approval, as well as potential benefits and disadvantages over traditional LHRH agonist therapy.

Expert opinion: Degarelix represents a newer class of ADT that results in a rapid and reliable decline in serum testosterone, a quality that makes it particularly advantageous in men presenting with symptomatic, hormone-sensitive prostate cancer. Due to differences in mechanism of action, there is observational data suggesting a potential cardiovascular and even oncologic benefit over traditional LHRH agonist therapy. Further research is ongoing to more clearly define this potential benefit.     

晚期前列腺癌治疗的回顾研究

目的比较间歇性雄激素阻断治疗（IAD）和持续性雄激素阻断治疗（CAD）在有骨转移的前列腺癌（PCAM≥1）的疗效以及不良反应。方法回顾2011年1月至2013年1月郑州大学附属肿瘤医院收治的90例前列腺癌患者,均经前列腺穿刺活检病理确诊为前列腺癌,ECT骨扫描证实有骨转移。其中44例患者采用皮下注射戈舍瑞林＋口服比卡鲁胺（IAD组）,46例患者采用双侧睾丸切除＋口服比卡鲁胺（CAD组）,当PSA〈0．2ug／L后,持续用药3个月停药,进入问歇期。待PSA〉4ng／ml后进人下一周期的治疗。比较两组患者由雄激素依赖性前列腺癌进展为雄激素非依赖性前列腺癌的时间、在治疗过程中生活质量以及不良反应的发生率。结果其中CAD组和IAD组患者发展为雄激素非依赖性前列腺癌的时间分别为（14．54±5．41）个月和（14．37±5．38）个月,两组的差别无统计学意义（P=0．885〉0．05）,CAD组患者潮热、乳房疼痛的发生率分别为52．2％和45．7％,IAD组为20．5％和18．2％。P〈0．05差别有统计学意义。结论iAD治疗在效果上与CAD大致相同,可在一定程度上缓解雄激素阻断治疗带来的副作用,提高生活质量。     

Effect of androgen deprivation therapy on the contractile properties of type I and type II skeletal muscle fibres in men with non‐metastatic prostate cancer

The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age‐ and activity‐matched healthy male subjects (Control). Mechanically‐skinned muscle fibres were exposed to a sequence of heavily Ca²⁺‐buffered solutions at progressively higher free [Ca²⁺] to determine their force‐Ca²⁺ relationship. Ca²⁺‐sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by ?0.05 and ?0.04 pCa units, respectively, P < .02), and specific force was around 13% lower in type I fibres of ADT subjects than in Controls (P = .02), whereas there was no significant difference in type II fibres. Treatment with the reducing agent dithiothreitol slightly increased specific force in type I and type II fibres of ADT subjects (by ~2%‐3%, P < .05) but not in Controls. Pure type IIx fibres were found frequently in muscle from ADT subjects but not in Controls, and the overall percentage of myosin heavy chain IIx in muscle samples was 2.5 times higher in ADT subjects (P < .01). The findings suggest that testosterone suppression can negatively impact the contractile properties by (i) reducing Ca²⁺‐sensitivity in both type I and type II fibres and (ii) reducing maximum specific force in type I fibres.