醋酸阿比特龙片联合醋酸泼尼松片治疗雄激素剥夺治疗失败转移性去势抵抗性前列腺癌患者的临床研究

目的 基于雄激素受体剪接变异体7(AR-V7)表达监测探究阿比特龙片联合泼尼松片治疗雄激素剥夺治疗(ADT)失败转移性去势抵抗性前列腺癌(mCRPC)患者的价值。方法 选取ADT治疗失败的mCRPC患者,且每天使用醋酸阿比特龙片1 000 mg联合泼尼松片5 mg进行治疗,治疗前采集外周静脉血进行循环肿瘤细胞AR-V7检测,根据AR-V7表达情况将患者分为AR-V7阳性组和AR-V7阴性组,统计并比较2组患者的一般资料、临床疗效、骨痛缓解率、前列腺癌患者生存质量测定量表(FACT-P)评分、前列腺特异性抗原(PSA)无进展生存期(PFS)、影像学PFS、总生存时间(OS)及药物不良反应发生情况。结果 入选60例患者,其中AR-V7阳性组21例和AR-V7阴性组39例。治疗后,AR-V7阳性组和AR-V7阴性组的总有效率分别为57.14%和82.05%,差异有统计学意义(P<0.05)。治疗后,AR-V7阳性组和AR-V7阴性组的FACT-P评分分别为(92.32±10.24)和(101.26±11.14)分,PSA PFS分别为7.00和12.00个月,影像学PFS分别为12.0...     

阿比特龙联合泼尼松用于未化疗转移性去势抵抗性前列腺癌治疗的效果及不良反应分析

目的 探讨阿比特龙联合泼尼松用于未化疗转移性去势抵抗性前列腺癌(mCRPC)治疗的效果及不良反应.方法 选取2019年1月～2019年12月于我院进行治疗的未化疗转移性去势抵抗性前列腺癌患者60例,随机分为两组,对照组采用泼尼松进行治疗,研究组联合阿比特龙进行治疗,对比两组患者干预前后f-PSA、PSA、OS以及不良反...     

阿比特龙潜在药物相互作用的医嘱调查

目的分析和总结转移性去势抵抗性前列腺癌患者使用阿比特龙和其他药物之间存在的潜在药物相互作用,为临床安全用药提供参考。方法采用回顾性分析方法,通过医院信息管理系统调取2016年1月-2018年8月本院使用阿比特龙的住院患者病历,并根据Lexicomp和MICROMEDEX 2.0数据库中的药物相互作用评价标准予以总结。结果 62例患者中,潜在有临床意义的药物相互作用发生率分别为55%(Lexicomp)和52%(MICROMEDEX 2.0)。结论阿比特龙潜在药物相互作用应引起高度重视,以减少其可能带来的用药风险。     

醋酸阿比特龙联合多西他赛与泼尼松在转移性去势抵抗性前列腺癌患者中的应用及Naa10与治疗敏感性的关系

目的 探讨醋酸阿比特龙联合多西他赛与泼尼松在转移性去势抵抗性前列腺癌（mCRPC）患者中的应用及N-末端α位乙酰基转移酶基因10（acetyltransferase gene 10,Naa10）与治疗敏感性的关系。方法 回顾性选择2017年10月-2019年12月邢台医学高等专科学校第二附属医院收治的122例mCRPC患者为研究对象,入选患者均经过雄激素剥夺治疗。根据治疗方案不同将患者分为对照组和试验组,对照组患者静脉滴注多西他赛注射液,剂量75 mg·m^-2,每3周1次;口服醋酸泼尼松片,1次1片,每天2次;在注射多西他赛注射液化疗前1天、当天和后1天均口服醋酸地塞米松片,1日2次,总剂量7.5 mg。试验组患者在对照组的基础上空腹口服醋酸阿比特龙片,每次1 g,每日1次,治疗4个周期（12周）。比较两组患者近期临床疗效、不良反应及远期生存率等情况,随访3年,计算患者的中位生存期。免疫组化法检测mCRPC癌组织中Naa10蛋白表达,将患者分成Naa10阳性表达组和阴性表达组,分析其临床病理参数,单因素和Cox回归分析确定影响mCRPC预后的因素,分析Naa10蛋白阳性表达与治疗敏感性的关系。结果 治疗4个周期后,试验组患者9例完全缓解、40例部分缓解、8例疾病稳定及4例疾病进展,治疗总有效率为80.33%;对照组患者2例完全缓解、34例部分缓解、20例疾病稳定及5例疾病进展,治疗总有效率为59.02%,两组间比较差异显著（χ²=6.556,P=0.011）。试验组和对照组患者均出现骨髓抑制（χ²=0.209,P=0.648）、肝功能损伤（χ²=0.830,P=0.362）、胃肠道反应（χ²=0.370,P=0.543）、水钠潴留（χ²=0.209,P=0.648）及心脏毒性（χ²=0.899,P=0.343）等3级以上不良反应,但两组间差异未见显著性。mCRPC癌组织中Naa10蛋白阳性表达与治疗周期（χ²=9.106,P=0.003）、淋巴结转移（χ²=5.055,P=0.025）、T分期（χ²=4.391,P=0.036）、骨转移病灶数（χ²=19.863,P=0.000）、内脏转移（χ²=5.009,P=0.025）等具有显著相关性,但与年龄（χ²=3.059,P=0.080）、化疗方案（χ²=0.880,P=0.348）、EOCG评分（χ²=3.453,P=0.178）、民族（χ²=0.135,P=0.713）及Gleason评分（χ²=0.837,P=0.360）等没有显著相关性。单因素分析结果显示,mCRPC患者中位生存期与EOCG评分（χ²=7.464,P=0.006）、淋巴结转移（χ²=6.114,P=0.013）、化疗方案（χ²=7.049,P=0.030）、治疗周期（χ²=5.051,P=0.038）、T分期（χ²=1.196,P=0.035）、骨转移病灶数（χ²=9.611,P=0.008）、内脏转移（χ²=1.085,P=0.048）及Naa10蛋白阳性表达（χ²=15.600,P=0.000）等指标具有显著相关性。Cox回归分析结果显示,骨转移病灶数（>10个）（OR=2.404,95% CI：1.424~4.056）、治疗周期（>8个疗程）（OR=0.458,95% CI：0.253~0.832）、化疗方案（试验组）（OR=0.360,95% CI：0.160~0.801）和Naa10蛋白阳性表达（OR=2.563,95% CI：2.106~3.117）是mCRPC患者预后生存的独立影响因素（P<0.05）。结论 醋酸阿比特龙联合多西他赛与泼尼松应用于mCRPC治疗,可有效提高近期临床疗效,延长生存期,且不增加不良反应,同时Naa10蛋白高表达是mCRPC患者预后不良的危险因素,临床宜监测指标,及时调整和评估临床治疗效果。     

醋酸阿比特龙对戈舍瑞林去势抵抗性前列腺癌细胞化疗敏感性的影响

目的 探讨醋酸阿比特龙(AA)对戈舍瑞林去势抵抗性前列腺癌(CRPC)PC3细胞化疗敏感性的影响.方法 CRPC PC3细胞分为空白组、对照组、实验组和联合组,用不含药、含20％致死浓度(IC20)多西他赛、含IC20 AA、多西他赛IC20 AA+IC20多西他赛的细胞培养液进行干预.用噻唑蓝法检测细胞的增殖情况,用...     

阿比特龙治疗去势抵抗性前列腺癌老年患者的临床效果

目的:探讨阿比特龙治疗去势抵抗性前列腺癌(CRPC)老年患者的临床疗效.方法:将我院泌尿外科2017年6月至2019年4月期间收治的120例CRPC老年患者,随机将其为各有60例患者的两组:观察组和对照组.观察组联合应用醋酸阿比特龙与泼尼松治疗,对照组单纯应用泼尼松治疗.比较两组患者的临床疗效,治疗前后检测两组患者血清PSA和中性粒细胞计数水平,对比治疗期间两组患者发生不良反应的情况.结果:观察组患者在临床治疗总有效率方面较对照组显著提高(86.67％VS 71.67％),差异具有显著性(P<0.05).两组患者血清PSA水平和中性粒细胞计数治疗后均明显降低(P<0.05),观察组血清PSA水平治疗后显著低于对照组,中性粒细胞计数治疗后高于对照组(P<0.05).观察组治疗期间的药物不良反应总发生率较对照组比较,差异无显著性(P>0.05).结论:CRPC老年患者应用阿比特龙治疗后,血清PSA水平得到有效控制,取得的临床效果满意,且不良反应发生率低,值得临床进行大力推广应用.     

多西紫杉醇、泼尼松联合阿比特龙对激素抵抗型前列腺癌血清肿瘤标志物水平的影响观察

目的：观察多西紫杉醇、泼尼松联合阿比特龙对激素抵抗型前列腺癌患者血清肿瘤标志物水平的影响。方法：选 取 2016 年 2 月—2019 年 3 月在本院进行化疗的激素抵抗型前列腺癌患者 68 例,按随机数字表法分为观察组和对照组各34 例。对照组给予多西紫杉醇、泼尼松治疗,观察组在对照组基础上联合阿比特龙治疗,观察两组患者的血清肿瘤标志物水平变化。结果：治疗后,总有效率观察组（88.24%）明显高于对照组（64.71%）,两组差异有统计学意义（P＜0.05）;观察组血清肿瘤标志物水平及免疫功能水平均优于对照组,组间差异有统计学意义（P＜0.05）。结论：多西紫杉醇、泼尼松联合阿比特龙治疗激素抵抗型前列腺癌临床效果明显,可控制肿瘤恶化并提高患者免疫功能。     

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。     

二代雄激素受体抑制剂治疗非转移性去势抵抗性前列腺癌的快速卫生技术评估

目的 对二代雄激素受体抑制剂治疗非转移性去势抵抗性前列腺癌(nmCRPC)的安全性、有效性和经济性进行初步评估,以满足决策者的需要。方法 系统检索计算机检索pubmed、embase、the cochrane library、NHS EED和CADTH等英文数据库,中国知网(CNKI)、万方数据库和重庆维普(VIP)等中文数据库,搜集达罗他胺(Darolutamide),恩扎卢胺(Enzalutamide),阿帕他胺(Apalutamide)治疗nmCRPC的系统评价/Meta分析、经济学研究以及HTA报告,由2名评价者根据纳入排除标准提取数据.对结果进行定性分析。结果 共纳入系统评价/Meta分析18篇,经济学评价1篇,恩扎卢胺和阿帕他胺与达罗他胺间接比较无转移生存期(MFS)较高;总生存期(OS)相近无显著差异;阿帕他胺提供最大无进展生存期(PSA-PFS)的可能性最高,其次是恩扎卢胺。在涉及不良事件(AEs)的情况下,达罗他胺是首选剂,经济性方面,达罗他胺相较于其他两种药物治疗nmCRPC,成本-效果更好。结论 三种二代雄激素受体抑制剂治疗非转移性去势抵抗性前列腺癌均有显著优势,...     

Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer

Introduction: Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain.

Areas covered: We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17. In addition to discussing the clinical evidence, we also address evolving evidence of mechanisms of resistance and clinical cross-resistance during sequential therapy with these agents.

Expert opinion: AA and enzalutamide have both demonstrated tolerability and clinical benefit for multiple outcomes in patients with CRPC, in both post-chemotherapy and pre-chemotherapy settings. Both agents target the androgen-signaling pathway and have similar efficacy; however, they differ in prednisone use and their toxicity profiles, impacting the decision of upfront therapy. Mechanisms of resistance emerging after treatment include both alterations in AR signaling as well as mechanisms that bypass the AR. Retrospective analyses have demonstrated evidence that sequential treatment with these agents results in limited clinical benefit, supporting mechanisms of cross-resistance. Trials are ongoing to determine optimal timing, sequence and combination of these agents.     

前列腺癌去势疗法与糖尿病相关性的Meta分析

目的 探讨去势疗法是否会增加前列腺癌（PCa）患者罹患糖尿病的风险。方法 系统检索Medline、Embase、Cochrane Library Central关于去势疗法（ADT）应用于PCa并报道该治疗与糖尿病相关性的临床试验研究,对文献进行数据提取及Meta分析。结果 共8项临床研究,涉及65 695名应用ADT及91 893名未应用去势疗法（non-ADT）的PCa患者纳入分析。应用ADT的患者其糖尿病的发病率较non-ADT者高出39%[RR=1.39,95%CI（1.27~1.53）,P<0.01];亚组分析发现,不同的ADT对糖尿病发病率亦有不同的相关性,促雄性激素释放激素抑制剂能明显增加PCa患者罹患糖尿病的风险[RR=1.45,95%CI（1.36~1.54）,P<0.01];促雄性激素释放激素抑制剂联合口服抗雄性激素药物[RR=1.40,95%CI（1.01~1.93）,P<0.01],以及睾丸切除术也可明显增加糖尿病患病的风险[RR=1.34,95%CI（1.20~1.50）,P<0.01],而单纯服用抗雄性激素的药物则与糖尿病无明显相关性[RR=1.33,95%CI（0.75~2.36）,P=0.33]。结论 ADT可明显增加PCa罹患糖尿病的风险,提示临床应用该疗法需考虑采取相应的预防措施。     

Sipuleucel-T: in metastatic castration-resistant prostate cancer

Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T, patients undergo a leukapheresis procedure for collection of autologous peripheral blood mononuclear cells. Preparation of sipuleucel-T involves enrichment for antigen-presenting cells from the leukapheresis product and activation ex vivo with a recombinant fusion protein (PA2024). In the randomized, double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC, sipuleucel-T was associated with a 22% relative reduction in the risk of death (hazard ratio 0.78; p?=?0.03), which was the primary endpoint of the trial. After a median follow-up period of 34.1 months, median survival was 4.1 months longer with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant between-group difference for the median time to objective disease progression (a secondary endpoint). Almost all patients treated with sipuleucel-T in clinical trials reported an adverse event, although these were mild or moderate in severity (grade 1 or 2) in most patients. The most common adverse events (e.g. infusion-related events, such as chills and fever) generally occurred within the first day after administration of sipuleucel-T and resolved within 2 days.     

Advancing therapies in metastatic castration-resistant prostate cancer

ABSTRACT

Introduction: Prostate cancer is the second most common cause of cancer worldwide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the cornerstone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatments have dramatically improved overall survival of men with mCRPC. Current therapies are based on AR-axis inhibitors and taxane-based chemotherapies, as well as radiopharmaceuticals and Sipuleucel T.

Areas covered: The authors provide a review of the current field of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies.

Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, as well as in non-metastatic castration-resistant patients, it is expected that a growing subgroup of patients will be exposed earlier to chemotherapy and to AR targeted agents. It becomes then fundamental to find novel strategies to overcome drug resistance and further improve survival.     

Controversies of androgen ablation therapy for metastatic prostate cancer

Ever since Huggins and Hodges won a Nobel Prize in 1966 for their work describing the relationship between testosterone and prostate cancer, androgen deprivation has continued to be an important component in the treatment of prostate cancer. Refinements in the therapy have occurred in the past 50 years, yet controversies still exist. This review details the controversies and advances in androgen deprivation for prostate cancer including: neoadjuvant androgen deprivation, combined androgen blockade, early versus late androgen deprivation treatment, intermittent versus continuous androgen deprivation monotherapy, anti-androgen monotherapy, anti-androgen and 5-alpha reductase inhibitor combinations, androgen deprivation with periodic intravenous bisphosphonate infusions, and androgen deprivation in conjunction with chemotherapy.     

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.     

雄激素去除治疗对老年男性前列腺癌患者骨代谢的影响

目的 探讨雄激素去除治疗的老年男性前列腺癌患者骨代谢的变化.方法 检测病理确诊为前列腺癌的老年男性患者40例(治疗组)治疗前及治疗1年后相关血清骨代谢标志物,包括骨钙素(OC)、总Ⅰ型前胶原氨基端肽(tPINP)、Ⅰ型胶原羧基端肽(β-CTx)、甲状旁腺激素(PTH)、钙(Ca)和磷(P).结果与同期体检正常的老年男性40例(对照组)比较.结果 治疗前两组相关骨代谢指标差异无统计学意义(P＞0.05).1年后,治疗组的tPINP和β-CTx较对照组明显升高(P＜0.05).结论 检测血清tPINP和β-CTx可以帮助临床评估行雄激素去除治疗的老年男性前列腺癌患者骨代谢的变化.