间歇性与持续性雄激素阻断治疗晚期前列腺癌疗效比较

目的：比较间歇性与持续性雄激素阻断治疗晚期前列腺癌的疗效以及治疗产生的副作用。方法选取我科2012年1月-2013年1月收治的晚期前列腺癌患者76例,分为观察组（38例）及对照组（38例）。观察组38例行间歇性雄激素阻断治疗即药物去势加抗雄激素药物,对照组38例行持续性雄激素阻断治疗即手术去势加抗雄激素药物。比较两组患者的副反应发生率及治疗后的生活质量。结果观察组38例患者发生潮热症状者13例（34.21％）、乳房胀痛者12例（31.58％）。对照组23例患者发生潮热症状者26例（68.42％）、乳房胀痛者25例（65.79％）。比较两组潮热症状及乳房胀痛的发生率差异均有统计学意义（P＜0.05）。两组患者治疗后,观察组患者在肠道症状、性功能、尿路症状、骨痛、治疗相关症状方面都较对照组有明显的改善,生活质量大大提高,两组对比差异有统计学意义（P＜0.01）。结论间歇性联合雄激素阻断治疗可以明显降低患者治疗的副作用并且增加治疗后的生活质量,是晚期前列腺癌患者行雄激素阻断治疗的首选方案。     

前列腺癌患者雄激素撤除治疗后的不良事件及对策

雄激素撤除治疗（ADT）在前列腺癌治疗中占有较高比例，广泛应用于局限性进展期前列腺癌、转移性前列腺癌及前列腺癌根治术后PSA复发者。前列腺癌患者撤除雄激素的结果是使患者产生比一般中老年男子雄激素部分缺乏综合征更加强烈的雄激素缺乏症状，其中比较明显的症状包括潮热、骨质疏松／骨折、性功能障碍、贫血、乳腺发育、肌容量减少、抑郁以及全面的生活质量（QOL）降低。     

唑来膦酸与阿仑膦酸钠治疗骨质疏松性髋部骨折的临床疗效对比

目的回顾性分析唑来膦酸与阿仑膦酸钠对骨质疏松性髋部骨折患者的临床疗效和安全性比较。方法从2016年1月至2017年10月就诊的骨质疏松性髋部骨折患者中筛选出分别接受唑来膦酸和阿仑膦酸钠治疗至少1年的老年患者作为研究对象,分为观察组(唑来膦酸治疗)和对照组(阿仑膦酸钠治疗)。收集所有患者治疗前及治疗1年后视觉模拟评分(VAS)、股骨骨密度和骨代谢标志物变化情况,进行组间比较,观察药物不良反应和再发骨折情况。结果治疗1年后两组患者术后骨密度明显升高,VAS评分、Ⅰ型胶原氨基端前肽(PINP)、Ⅰ型胶原羧基端肽(CTX)水平较治疗前均显著下降(P均0. 05)。治疗后观察组VAS评分、CTX水平显著低于同期对照组(P0. 05),两组骨密度、PINP、药物不良反应发生率以及再发骨折差异均无统计学意义(P0. 05)。结论唑来膦酸和阿仑膦酸钠用于骨质疏松性髋部骨折均安全有效。但在缓解骨折术后骨痛症状,改善骨代谢,提高患者依从性方面,唑来膦酸优于阿仑膦酸钠。     

唑来膦酸联合骨水泥技术治疗老年骨质疏松性骨折的疗效分析

目的探讨唑来膦酸(密固达)联合骨水泥技术治疗老年骨质疏松性骨折的临床疗效。方法回顾性分析我科于2010~2011年收治老年骨质疏松性骨折并行PVP/PKP骨水泥技术治疗的病人,20例获得随访,依据PVP/PKP术后是否应用唑来膦酸治疗,分成对照组及实验组。所有病人分别于治疗前和治疗后1年进行股骨近端骨密度测量及疼痛VAS临床评分,评价治疗效果。结果治疗1年后实验组患者股骨近端骨密度明显提高,脊柱骨疼痛症状较对照组得到持续缓解,治疗后1年内无新发骨折。对照组1年期间有脊柱骨性疼痛加重趋势,1例患者术后2月后再次出现新发椎体骨质疏松性骨折。唑来膦酸用药后主要临床不良反应为类流感样反应,包括发热、面红、周身不适等,短期内可缓解,患者均可耐受。结论唑来膦酸联合骨水泥技术治疗老年骨质疏松性骨折效果显著,可明显提高骨质疏松性患者骨密度,预防骨量持续丢失,提高患者生活质量,并有效减轻全身及胸腰部骨性疼痛症状,预防再次骨折发生。应用唑来膦酸给药方便、依从性较好,不良反应轻微、可达到全身系统化治疗,可作为骨质疏松性骨折PVP术后一种良好的辅助治疗措施。     

89锶、唑来膦酸及99锝-亚甲基二膦酸盐治疗老年前列腺癌骨转移的临床观察

［摘要］ 目的 观察和比较89Sr、唑来膦酸及99锝-亚甲基二膦酸盐（云克）在老年前列腺癌骨转移患者治疗中的临床价值。方法 回顾性分析2017年01月至2018年01月我科收治的老年前列腺癌骨转移患者，分为89Sr治疗组、唑来膦酸治疗组及云克治疗组。比较三组患者治疗后骨痛缓解、骨转移灶控制及不良反应情况，并行统计学分析。结果 本研究共纳入53例患者，镇痛疗效：89Sr组较唑来膦酸组、云克组治疗早期止痛效果好，差异有统计学意义（P<0.05），但治疗6个月后差异减小，12个月后三组间差异无明显统计学意义（P>0.05）。89Sr组及唑来膦酸组对重度疼痛组缓解优于中度疼痛组，无明显统计学差异（P>0.05），云克组对重度疼痛组缓解明显差于中度疼痛组，有统计学差异（P<0.05）。转移灶疗效：89Sr组较唑来膦酸组、云克组治疗效果好，但无明显统计学差异。骨转移灶数目，89Sr组及唑来膦酸组、云克组对≥10组的治疗效果优于<10组，但均无明显统计学差异。不良反应：89Sr的骨髓抑制、唑来膦酸的发热反应，较另两种药物有明显统计学差异（P<0.05），其余不良反应无明显统计学差异（P>0.05）。结论 89Sr、唑来膦酸、云克均有较好的缓解骨痛、控制骨进展作用。89Sr针对老年患者，易出现骨髓抑制，需密切随访。云克不良反应少，连续长期静脉输液，增加老年患者的痛苦。唑来膦酸易出现发热，但给予对症后可缓解。     

晚期前列腺癌的雄激素阻断治疗

目的探讨间歇性雄激素阻断治疗与持续性雄激素阻断治疗晚期前列腺癌的疗效和不良反应。方法65例晚期前列腺癌患者分为两组，A组34例行间歇性雄激素阻断（IAB）治疗，B组31例行持续性雄激素阻断（CAB）治疗，比较两组在疾病进展时间和不良反应方面的差异。结果A组中位随访时间为37．0个月，B组中位随访时间为35．8个月。A、B组疾病进展率分别为29．4％和54．8％，两组比较差异有统计学意义（P=0．038）。A、B组疾病中位进展时间分别为34．9个月、28．4个月，两组比较差异有统计学意义（P=0．0018）。在有骨转移患者中，A、B组疾病中位进展时间分别为33．6个月、27．1个月，两组比较差异有统计学意义（P=0．020）。在无骨转移患者中，A、B组疾病中位进展时间分别为38．7个月、30．3个月，两组比较差异有统计学意义（P=0．0006）。不良反应发生率分别为A组发生潮热症状23．5％、乳腺肿痛17．6％、骨质疏松14．7％。B组发生潮热症状64．5％、乳腺肿痛54．8％、骨质疏松45．2％。两组比较差异有统计学意义：潮热症状P=0．0006，乳腺肿痛P=0．0014，骨质疏松P=0．0065。结论对晚期前列腺癌患者IAB治疗可以延缓病变的进展，减少雄激素阻断导致的不良反应，提高患者的生活质量，应作为晚期前列腺癌患者的首选治疗。     

唑来膦酸对新疆维吾尔族老年男性骨质疏松患者的疗效观察

目的 探讨注射用唑来膦酸5mg对新疆维吾尔族老年男性骨质疏松患者的临床疗效。方法 选取2010年6月至2011年11月住院期间维吾尔族老年男性骨质疏松患者43例,所有患者均初次诊断为骨质疏松症,未曾行任何抗骨质疏松治疗,同时排除其他骨代谢性疾病或药物影响,随机分为治疗组（22例,平均年龄73.2岁）,给予唑来膦酸5mg,静脉滴注30min,同时口服钙尔奇600mg/d及阿尔法D3 0.25μg/d;对照组（21例,平均年龄73.8岁）,给予口服钙尔奇600mg/d及阿尔法D3 0.25μg/d,治疗时间1年,采用双能X线骨密度仪(DXA)测定两组治疗前后的腰椎1-4、股骨颈、Wards三角区骨密度值。结果 排除治疗组中2例患者脱失外,治疗组骨密度增幅程度均显著高于对照组（P＜0.05）。5例患者在注射唑来膦酸后出现发热、头痛及流感样症状,给予NSAIDs对症治疗后5例患者均在3d内缓解,未见其他不良反应。结论 唑来膦酸注射液5mg可明显提高新疆维吾尔族老年男性骨质疏松患者的骨密度,抑制骨量丢失,降低骨折风险,提高患者依从性,不良反应可耐受,是治疗新疆维吾尔族老年男性骨质疏松患者的新一类高效药物。     

唑来膦酸治疗血液透析患者继发性甲状旁腺功能亢进合并骨质疏松的疗效分析

目的评价唑来膦酸注射液治疗维持性血液透析患者继发性甲状旁腺功能亢进合并骨质疏松的临床疗效及安全性。方法回顾性分析2013~2014年在我院行维持性血液透析治疗的继发性甲状旁腺功能亢进合并骨质疏松的患者8例,给予唑来膦酸注射液治疗,观察治疗前、治疗后6个月和12个月的血清全段甲状旁腺激素(intact parathyroid hormone,iPTH)、钙、磷、碱性磷酸酶、白细胞、血小板水平的变化情况。测量治疗前及治疗12月后患者腰椎、左右侧股骨颈的骨密度,记录用药后不良反应及患者临床症状改善情况。结果与治疗前比较,治疗6月及12月后血清iPTH、钙明显下降,差异有统计学意义;治疗后6个月与治疗12月后相比,血清iPTH、钙水平虽有所下降,但差异无统计学意义。血清磷、碱性磷酸酶等指标与治疗前相比,有下降趋势,但差异无统计学意义。唑来膦酸治疗12个月后,患者腰椎、左右股骨颈骨密度均有不同程度的增高,差异有统计学意义。用药后有1例患者出现肌肉关节酸痛,对症处理后其症状缓解;1例患者血小板轻度降低,其余尚未观察到其他不良反应,可能与研究病例数较少有关;3例患者自觉骨痛症状较前缓解。结论唑来膦酸注射液可有效降低维持性血液透析继发性甲状旁腺功能亢进合并骨质疏松患者的血iPTH、血清钙水平,增加骨密度,缓解骨痛症状,且安全性好。     

唑来膦酸与特立帕肽对骨质疏松患者腰椎椎间融合影响的对比分析

目的:比较唑来膦酸与特立帕肽对骨质疏松患者腰椎间融合的影响.方法:前瞻性纳入2016年3月至2018年10月行后路腰椎间融合术合并骨质疏松患者91例,根据患者自行选择接受的治疗方式分为基础对照组22例、唑来膦酸组39例和特立帕肽组30例,分别采用基础抗骨质疏松治疗、辅助唑来膦酸或者特立帕肽抗骨质疏松治疗促进椎间骨融合....     

89锶、唑来膦酸及99锝-亚甲基二膦酸盐治疗老年前列腺癌骨转移的临床观察

目的观察和比较89Sr、唑来膦酸及99锝-亚甲基二膦酸盐(云克)在老年前列腺癌骨转移患者治疗中的临床价值。方法回顾性分析2017年01月至2018年01月我科收治的老年前列腺癌骨转移患者,分为89Sr治疗组、唑来膦酸治疗组及云克治疗组。比较三组患者治疗后骨痛缓解、骨转移灶控制及不良反应情况,并行统计学分析。结果本研究共纳入53例患者,镇痛疗效:89Sr组较唑来膦酸组、云克组治疗早期止痛效果好,差异有统计学意义(P0.05),但治疗6个月后差异减小,12个月后三组间差异无明显统计学意义(P0.05)。89Sr组及唑来膦酸组对重度疼痛组缓解优于中度疼痛组,无明显统计学差异(P0.05),云克组对重度疼痛组缓解明显差于中度疼痛组,有统计学差异(P0.05)。转移灶疗效:89Sr组较唑来膦酸组、云克组治疗效果好,但无明显统计学差异。骨转移灶数目,89Sr组及唑来膦酸组、云克组对≥10组的治疗效果优于10组,但均无明显统计学差异。不良反应:89Sr的骨髓抑制、唑来膦酸的发热反应,较另两种药物有明显统计学差异(P0.05),其余不良反应无明显统计学差异(P0.05)。结论89Sr、唑来膦酸、云克均有较好的缓解骨痛、控制骨进展作用。89Sr针对老年患者,易出现骨髓抑制,需密切随访。云克不良反应少,连续长期静脉输液,增加老年患者的痛苦。唑来膦酸易出现发热,但给予对症后可缓解。     

Androgen deprivation therapy-associated vasomotor symptoms

Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hormonal therapy of hot flashes has been shown to be effective, multiple non-hormonal medications and treatment methods have also been developed. This article reviews current options for the treatment of hot flashes in patients taking ADT.     

Improving intermittent androgen deprivation therapy： lessons learned from basic and translational research

Intermittent androgen deprivation therapy （IADT） is an alternative to continuous androgen deprivation therapy （ADT） in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic.     

Complications of androgen-deprivation therapy in men with prostate cancer

Androgen-deprivation therapy (ADT) is indicated for the treatment of metastatic prostate cancer and locally advanced disease. In addition to sexual side effects, long-term ADT results in several other changes, including hot flashes; gynecomastia; changes in body composition, metabolism, and the cardiovascular system; osteoporosis; anemia; psychiatric and cognitive problems; and fatigue and diminished quality of life. This review discusses these complications of ADT and treatments aimed at reducing them. It is important for clinicians to anticipate these effects and to initiate measures to prevent or minimize them in order to maintain quality of life in prostate cancer survivors.     

Use of androgen deprivation therapy for metastatic prostate cancer in older men

OBJECTIVE

To assess factors associated with early or delayed androgen deprivation therapy (ADT) among men diagnosed with metastatic prostate cancer, and to assess the relationship between ADT and overall survival, as there is uncertainty about the ideal timing for initiating ADT in men with metastatic prostate cancer.

PATIENTS AND METHODS

We studied a population‐based cohort of American men aged ≥66 years diagnosed with metastatic prostate cancer during 1992–2002 and followed to 2003. We assessed the receipt of ADT early (≤4 months from diagnosis), delayed (>4 months), or not at all, using multinomial logistic regression to identify factors associated with treatment, and Cox proportional‐hazard models to assess whether treatment was associated with survival.

RESULTS

Overall, 69.5% of men received early ADT and 7.3% delayed. Adjusted rates of early ADT were lower for black than white men (58.3% vs 71.0%), and of delayed ADT were higher for black than white men (12.7% vs 6.2%). Receipt of ADT was associated with improved survival (adjusted hazard ratio 0.69, 95% confidence interval 0.66–0.73). The benefit of early treatment did not differ from delayed treatment (P = 0.58).

CONCLUSIONS

A large minority of men with metastatic prostate cancer, particularly black men, receive delayed or no ADT. Early or delayed ADT was associated with similarly prolonged survival. After controlling for patient and tumour characteristics, survival did not differ by race, and receipt of ADT did not contribute to racial differences in survival.     

Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer

PURPOSE: Luteinizing hormone releasing hormone (LHRH) agonist therapy for advanced prostate cancer can manifest significant side effects affecting quality of life, most notably hot flashes. This study evaluated the effectiveness of parenteral medroxyprogesterone acetate (MPA) in reducing the frequency and severity of these hot flashes. MATERIALS AND METHODS: A multi-institutional retrospective review of hot flashes from LHRH therapy for prostate cancer was conducted. The hot flashes were quantified and the severity was graded (3-point analogue scale) before and after treatment with MPA. Two doses of MPA (400 or 150 mg intramuscularly) were administered. Statistical analysis (Student's t test) evaluated the quantity of hot flashes, the quality of hot flashes, and dose effectiveness. RESULTS: A total of 48 men (40 at 400 mg, 8 at 150 mg) with a mean age of 71.4 years (range 54 to 87) from 3 institutions were evaluated. There were 91% with symptomatic improvement with MPA, and half (46%) had a complete response defined as total elimination of hot flashes. The median number of the hot flashes per day decreased from 4 to 1 and the median severity score decreased from 2 to 1 (p <0.05). Significance was not achieved comparing the 2 doses. Complete responders were not noted with the 150 mg dose. Anticipated response to MPA did not correlate with the number or severity of the hot flashes. CONCLUSIONS: This study is the first multi-institutional evaluation of hot flashes demonstrating significant reduction in quantity and severity with MPA. Based on these data we now manage hot flashes associated with LHRH analogues with 400 mg of MPA.     

Quality of life following endocrine therapy for advanced prostate cancer: a comparative study between LH-RH agonist 1-month depot and 3-month depot

PURPOSE: There were few studies which reported the longitudinal quality of life (QOL) for Japanese men who received endocrine therapy for advanced or metastatic prostate cancer. A pilot randomized trial was conducted to assess QOL and the incidence of hot flash following endocrine therapy using luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate 1-month or 3-month depot alone in patients with advanced or metastatic prostate cancer. MATERIAL AND METHODS: A total of 28 patients with advanced or metastatic prostate cancer who received LH-RH analogue goserelin acetate depot alone for 12 months were randomized (1:1) to two different formulations. Fifteen patients received the 1-month depot and thirteen patients received 3-month depot, namely Zoladex 3.6 mg depot and Zoladex LA 10.8 mg depot, respectively. We measured health related QOL using European Organization for Research and Treatment of Cancer (EORTC) and EuroQol (EQ-5D) questionnaire and evaluated the incidence of hot flashes between the two groups for one year after diagnosis. Moreover, we evaluated the incidence of hot flashes between the 1M and 3M depot. A baseline interview was conducted before treatment. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 9 and 12 months after treatment. RESULTS: Five (18%) patients dropped out of the study. Thus, we analyzed 23 eligible patients (11 in the 1M arms and 12 in the 3M arms). No significant differences between the two treatment arms were detected in categories of age, average pre- PSA values, Gleason scores and clinical T stage. According to EORTC, each treatment group showed similar QOL scores in all domains before and after treatment. With regard to EQ-5D, the 1M-treatnent arm reported better utility scores than 3M treatment arm, which was no significant statistically. The overall incidence of hot flash was 61% (58% in 1M group and 64% in 3M group). CONCLUSION: There were no differences with regard to general and disease specific HRQOL between the both formulations of goserelin acetate. Hot flashes are the major adverse effects of endocrine therapy for Japanese patients with prostate cancer.     

Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate

PURPOSE: In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration. MATERIALS AND METHODS: We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance. RESULTS: Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes. CONCLUSIONS: Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.     

去势治疗对前列腺癌患者骨密度的影响

目的 :探讨去势治疗对前列腺癌患者骨密度 (BMD)的影响。　方法 :4 9例完成BMD测定的前列腺癌患者分为 2组 :非去势组 2 1例 ,在去势治疗前即已完成BMD测定 ;去势组 2 8例 ,均为去势治疗 1年以上者。BMD测定采用双能X线吸收法 (DEXA法 ) ,测定部位为腰椎 (L2～ 4)和股骨颈。为校正年龄、性别和体重因素对BMD的影响 ,与年龄、种族等相配对的Z评分被用于结果评估。　结果 :13例 (6 2 % )非去势组患者和 2 3例 (82 % )去势组患者均存在不同程度的BMD水平下降。在非去势组 ,腰椎 (L2～ 4)Z评分为 - (0 .9± 0 .7)分 ,股骨颈Z评分为 - (0 .6± 0 .5 )分 ;而在去势组 ,腰椎 (L2～ 4)Z评分为 - (1.8± 1.1)分 ,股骨颈Z评分为 - (1.6± 1.0 )分。与非去势组相比 ,去势组患者BMD水平明显偏低 ,差异有显著性 (P <0 .0 1)。　结论 :去势治疗前 ,前列腺癌患者常伴有不同程度的骨量减少和骨质疏松 ,去势治疗与前列腺癌患者BMD水平下降明显相关。在对前列腺癌患者采用去势治疗之前 ,BMD测定是必要的。     

药物去势联合雄激素受体阻断剂治疗晚期前列腺癌(附5年临床观察)

目的 观察药物去势联合雄激素受体阻断剂(氟硝丁酰胺，Flutamide)治疗晚期前列腺癌的疗效及药物去势的稳定性。方法 回顾性分析35例药物去势加雄激素阻断剂治疗晚期前列腺癌的I临床资料。结果 所有病人应用LHRH-A 1个月后血睾酮降至去势水平，持续给药可维持稳定的去势水平。34例有治疗效果，有效率97．1％。经平均38．4月随访，复发率为11．8％。7例出现肝功能异常，15例出现食欲减退，35例出现性欲减退和勃起障碍，2例出现血像异常，16例出现潮热、盗汗。结论 药物去势联合雄激素阻断剂治疗初发的晚期前列腺癌疗效肯定，去势稳定。