帕米膦酸二钠联合^89Sr治疗激素非依赖型前列腺癌骨转移疗效观察

目的：观察帕米膦酸二钠与^89Sr联合应用对激素非依赖型前列腺癌（PCa）伴骨转移的治疗效果。方法：将我院收治的29例激素非依赖型PCa伴骨转移患者随机分成A、B两组,A组采用帕米膦酸二钠90mg溶于5％葡萄糖500ml,缓慢滴注4周1次,共2次;B组静脉注射^89Sr Cl21．48mBq／kg,1周后与A组治疗方法相同。采用疼痛视觉模拟法（VAs）评定患者主观骨痛,生活质量（QOL）评分来判定疗效。结果：在疼痛评分方面B组治疗后评分显著低于A组,生活质量评分有效率的差异无统计学意义。结论：帕米膦酸二钠联合^89Sr治疗激素非依赖型PCa伴骨转移在疼痛缓解有效率上高于单独使用帕米膦酸二钠,同时表明帕米膦酸二钠与^89Sr具有协同作用,其在不良反应方面无明显增加。     

锶89与放疗在非小细胞肺癌骨转移骨痛治疗中的疗效比较

目的比较锶89与放疗在非小细胞肺癌骨转移骨痛治疗中的疗效及不良反应,指导临床应用。方法选取我院2011年8月～2013年8月期间收治的非小细胞肺癌骨转移患者50例,所有患者均经病理证实,磁共振骨显像明确骨转移。随机分为两组,1组选择锶89联合唑来膦酸治疗,2组选择放疗联合唑来膦酸治疗,监测患者骨痛动态变化、血常规、肝肾功及骨扫描病灶变化。结果锶89联合唑来膦酸组骨痛反应情况及病灶消退情况明显优于放疗联合唑来膦酸组（P〈0．05）。锶89联合唑来膦酸组患者出现白细胞及血小板降低者3例,经升血治疗后3d后恢复;放疗联合唑来膦酸组白细胞及血小板降低者12例,7例患者3d后恢复;锶89联合唑来膦酸组及放疗联合唑来膦酸组均未发现肝肾功能损伤。结论氯化锶（^89Sr）联合唑来膦酸辅助治疗非小细胞肺癌骨转移骨痛,相较于放疗能显著提高治疗效果,且骨髓抑制较轻,值得临床应用。     

89Sr联合茵福治疗前列腺癌骨转移的临床护理

目的总结89Sr联合注射用因卡膦酸二钠(商品名茵福,资福药业有限公司)治疗前列腺癌骨转移的护理经验及临床疗效。方法回顾性分析56例接受89Sr联合茵福治疗和护理的前列腺癌骨转移患者的临床资料。结果经治疗患者骨转移病灶疼痛感明显缓解,未发现明显不良反应。结论 89Sr联合双茵福治疗晚期骨转移的前列腺癌安全有效,及时的护理干预可明显缓解患者痛苦,提高患者生活质量及治疗依从性。     

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。     

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。     

唑来膦酸联合泰索帝治疗乳腺癌骨转移效果观察

目的评价唑来膦酸联合泰索帝治疗激素受体阴性乳腺癌多发骨转移的效果及安全性。方法 36例乳腺癌骨转移患者随机分为唑来膦酸联合泰索帝组(A组)及单用唑来膦酸组(B组),分别对两组进行治疗并比较和分析其效果。结果两组骨痛缓解率、生活质量改善及毒副作用无统计学差异。A组转移灶修复率66.7%(12/18),B组11.1%(2/18),两组比较,差异有统计学意义(P0.05)。结论唑来膦酸联合泰索帝对乳腺癌多发骨转移较单用唑来膦酸有较好的治疗作用。     

盐酸吗啡控释片联合帕米磷酸二钠治疗骨转移癌疼痛的效果观察

目的:探讨盐酸吗啡控释片联合帕米磷酸二钠治疗骨转移癌疼痛的效果。方法与结果:经病理证实的多发性骨转移癌疼痛患者76例,随机分为单用帕米磷酸二钠组(A组37例),盐酸吗啡控释片与帕米磷酸二钠合用组(B组39例)。两组中、重度疼痛各占94.6％、100％,两组总有效率分别为84％、100％;显著有效率分别为35％、87％,差异非常显著(P<0.01)。结论:帕米磷酸二钠和盐酸吗啡控释片联合应用治疗多发性骨转移癌疼痛患者在缓解疼痛,改善生活质量方面疗效显著。     

^89Sr联合Tc-99-MDP综合治疗骨转移瘤的临床疗效评价

目的观察综合治疗多发性骨转移瘤，缓解骨痛，改善生活质量的现实意义。方法121例骨转移瘤患者分别用^89Sr联合（Tc-99-MDP云克）、骨膦治疗，并对照观察疗效。结果^89Sr联合云克治疗组，有效率为83．9％，较骨膦组高，且有统计学差异，两组均有部分出现Ⅰ、Ⅱ级血液毒性反应。结论。^89Sr联合云克在治疗多发性骨转移瘤、改善患者生活质量有明显疗效。     

帕米膦酸二钠对人骨髓间充质干细胞增殖和成骨分化的影响

目的观察帕米膦酸二钠对人骨髓间充质干细胞(Mesenchymal stem cells,MSC)生物学特性的影响,以探索双磷酸盐导致骨组织损伤的机制。方法人骨髓MSC培养体系中加入不同浓度的帕米膦酸二钠,培养72 h后,MTT法测定490 nm光密度值,观察细胞增殖情况;培养1周后,流式细胞技术检测细胞表面分子表达。体外诱导MSC成骨分化,体系中加入1μg/mL帕米膦酸二钠,1周后PCR法测定细胞Runx-2表达水平,2周后组织化学法测定细胞内碱性磷酸酶活性,以细胞总蛋白量为参照,观察MSC成骨分化的差异。结果 MTT结果显示,在0.1~10μg/mL浓度范围内,帕米膦酸二钠抑制人骨髓MSC增殖,作用呈浓度依赖性,最低作用浓度为1μg/mL,72 h OD490显著低于对照组(P<0.01)。流式细胞检测显示,帕米膦酸二钠处理后,细胞仍均一表达CD44和CD73,不表达CD31和CD45。PCR及细胞化学结果显示,帕米膦酸二钠无促进MSC成骨分化作用,也未提高成骨诱导体系促分化效果。结论帕米膦酸二钠可抑制MSC增殖,不促进其体外成骨能力,可能是长期使用双磷酸盐导致骨损伤的机制之一。     

华蟾素联合帕米磷酸二钠治疗脊柱骨转移癌性疼痛的临床价值研究

目的 探讨华蟾素胶囊联合帕米磷酸二钠在治疗脊柱骨转移癌性疼痛方面的临床价值及安全性.方法 将本中心收住的70例恶性肿瘤伴脊柱骨转移患者随机分为治疗组与对照组各35例,对照组单独采用帕米磷酸二钠治疗,治疗组采用帕米磷酸二钠联合华蟾素胶囊,评估比较两组患者后期疼痛评分(NRS评分)、疼痛程度、降低止痛药物用量及相关不良反应等指标.结果 治疗组患者经联合治疗后,NRS评分显著低于对照组(2.11±0.85 vs 4.71±1.86;P<0.05),治疗组患者疼痛缓解总有效率显著优于对照组(65.71％vs 40％;P<0.05),治疗组患者的阿片类药物用量显著少于对照组(P<0.05),而两组不良反应无显著性差异(P>0.05).结论 华蟾素胶囊联合帕米磷酸二钠在辅助治疗恶性肿瘤伴脊柱骨转移癌性疼痛方面疗效显著,可以显著减少阿片类药物的用量,且不增加相关临床不良反应.     

Strontium-89 combined with doxorubicin in the treatment of patients with androgen-independent prostate cancer

We investigated the activity of a bone-targeting regimen consisting of strontium-89 and doxorubicin in the treatment of patients with androgen-independent prostate cancer. Three and 22 patients with androgen-independent prostate cancer and bone metastasis received doxorubicin at 15 mg/m² and 20 mg/m², respectively (intravenously by continuous infusion over 24 hours, once per week). All patients received strontium-89 55 μCi/kg, intravenously, every 3 months. Antitumor activity (a prostate specific antigen decrease of ≥75% from baseline) was seen in 32% of evaluable patients. Clinical benefit based on pain relief and performance improvement was achieved in 76% and 40% of patients, respectively. Strontium-89 combined with doxorubicin can be delivered with acceptable toxicities. Strontium-89 combined with doxorubicin is active in the treatment of androgen-independent prostate cancer and may be useful in future studies designed to optimize organ (bone)-specific therapies.     

前列腺癌骨转移性疼痛的综合治疗

目的 :探讨晚期前列腺癌骨转移性疼痛的综合治疗方法。　方法 :16例确诊为前列腺癌且有多个部位骨转移病灶伴有疼痛的患者 ,采用口服抗雄激素药物治疗的同时 ,辅以核素89Sr静脉内注射治疗和部分病灶放射治疗。　结果 :治疗后 ,疼痛缓解率 3个月为 75 .6 % ,6个月为 80 .5 % ,9个月为 6 3.4 % ;骨转移病灶数量明显减少。结论 :经过综合治疗后 ,本组晚期前列腺癌伴骨转移性疼痛的患者疼痛获得较为满意的缓解、甚至消失 ,从而改善了患者的生活质量。     

单纯内分泌与内分泌加内照射治疗晚期前列腺癌的疗效对比分析

目的：研究核素内照射改善前列腺癌骨转移引起的疼痛及对骨转移治疗的疗效，并与内分泌治疗进行比较。方法：对52例前列腺癌骨转移患者均采用双侧睾丸切除加氟他胺（250mg,3次／d)治疗。所有患者均于术前不同时间出现明显的疼痛症状，其中15例接受^89锶内照射治疗（148MBq静脉注射），8例接受^153Sm-EDT-MP内照射治疗（37MBq/kg静脉注射，1次／月）；29例未接受内照射治疗者作为对照组。结果：^89锶治疗组有14例患者疼痛明显缓解，占93．3％（14／15）；^153Sm-EDTMP治疗组有6例疼痛明显缓解，占75．0％（6／8）；单纯内分泌治疗组经调整药物剂量或结构后，疼痛明显缓解者仅9例，占31．0％（9／29）。^99Tcm-MDP全身骨显像示骨转移病灶出现不同程度的好转，其中^89锶治疗组有11例，占73．3％（11／15）；^153Sm-EDTMP治疗组有5例，占62．5％（5／8），而单纯内分泌组有7例，占24．1％（7／29）。^89锶治疗组3例、^153Sm-EDTMP治疗组有2例出现血白细胞和血小板明显下降，经对症治疗后恢复。结论：核素内照射治疗能改善前列腺癌骨转移引起的疼痛，并可不同程度地抑制肿瘤骨转移灶的生长，但必须密切观察血红蛋白、白细胞及血小板的变化。     

~(89)Sr治疗前列腺癌骨转移的研究进展

89Sr发射最大能量为1.46MeV的纯β射线,物理半衰期50.5d,很快在体内被成骨组织摄取,完全滞留在成骨性骨转移病灶内。在转移灶内的生物半衰期大于50d,而在正常骨内只有14d。在前列腺癌患者的肿瘤骨吸收剂量是正常骨的2～25倍。在骨肿瘤中的吸收剂量是(21±4)至(231±56)cGy/MBq。89Sr是前列腺癌骨转移患者骨痛的有效缓解药物,对骨疼痛的止痛有效率为80%。     

Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy.

Cyclical intravenous therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study, we evaluated the effect of this therapy on lumbar spine bone mass (bone mineral content [BMC]), size (bone volume [BV]), and density (volumetric bone mineral density [vBMD]). Results from 56 patients (age, 0.2-15.9 years; 25 girls) on long-term pamidronate treatment were compared with those of 167 patients who had not received pamidronate before densitometry. In all patients who received pamidronate, BMC, BV, and vBMD increased above levels expected for untreated patients (p < 0.001 in each case). After 4 years of treatment, BMC, BV, and vBMD were 154%, 44%, and 65% higher, respectively, in treated than in untreated patients who were matched for age and OI type. A multiple regression model showed that baseline BMC was negatively associated with the increase in BMC. In conclusion, the bone mass increase in pediatric OI patients receiving pamidronate is caused by increases in both bone size and density. Patients with larger deficits in bone mass at baseline have a more marked bone mass gain during therapy.     

Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome.

Clinical and histomorphometric outcome was compared between children with OI who had received pamidronate since infancy and age-matched patients who had never received pamidronate. Pamidronate was associated with improved vertebral shape and mass, higher cortical width, increased cancellous bone volume, and suppressed bone turnover. INTRODUCTION: Observations in small patient series indicate that infants with severe osteogenesis imperfecta (OI) benefit from treatment with cyclical intravenous pamidronate. However, detailed analyses of outcome are lacking for this age group. MATERIALS AND METHODS: Clinical outcome was evaluated in 29 children with OI types I (n = 3), III (n = 14), or IV (n = 12) who started pamidronate therapy before 2 years of age (age at treatment onset: median, 6 months; range, 2 weeks to 23 months) and who had completed 3 years of treatment (total annual pamidronate dose, 9 mg/kg). They were compared with a historical control group of 29 untreated children with severe OI who were matched for OI type and age at the 3-year treatment time-point. In addition, iliac bone histomorphometry was compared between 24 pamidronate-treated patients and 24 age-matched OI patients who had not received pamidronate. RESULTS: Morphometric evaluation of lumbar vertebrae (L(1)-L(4)) showed that the shape of vertebral bodies was better preserved in pamidronate-treated patients. This was accompanied by significantly higher lumbar spine areal and volumetric BMD (+110 and +96%, respectively) and a larger vertebral bone volume (+26%) on densitometry. Regarding mobility function, the Pediatric Evaluation of Disability Inventory gross motor score was 50% greater in the pamidronate group (p < 0.001). Iliac bone histomorphometry showed 61% higher cortical width and 89% higher cancellous bone volume in pamidronate-treated patients. Bone formation rate per bone surface in the pamidronate group was only 17% that of untreated patients. CONCLUSIONS: In conclusion, this study suggests that cyclical pamidronate treatment started in infancy leads to improved bone strength and better gross motor function but also suppresses bone turnover markedly. It is therefore prudent to reserve pamidronate treatment to infant OI patients who present with a moderate to severe phenotype.     

放射性核素89Sr治疗前列腺癌骨转移疼痛的临床研究

目的:探讨晚期前列腺癌骨转移疼痛治疗的方法,评价放射性核素89Sr的疗效与安全性。方法:对15例未接受过任何放疗的晚期前列腺癌骨转移疼痛患者,经静脉注射放射核素89Sr治疗。结果:疼痛治疗的有效率为86.7%,80%患者的肿瘤标记物PSA水平较治疗前轻度下降,26.6%患者出现造血功能抑制。结论:放射性核素89Sr治疗前列腺癌骨转移疼痛较为安全、有效,可以提高患者生活质量。     

Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases.

Bisphosphonate pharmacokinetics may affect individual responses. Skeletal retention of pamidronate infused monthly to patients with bone metastases was highly variable (12-98%) and did not diminish with time, showing the capacity of the skeleton to retain large amounts of bisphosphonate. Relationships between skeletal retention of pamidronate and rate of bone resorption are complex and depend on previous treatment and the total amount of retained bisphosphonate. INTRODUCTION: Bisphosphonates (BPs) given intravenously every 3-4 weeks are effective in the management of metastatic bone disease from breast cancer, but responses among patients vary, and it is not known whether current dose and dose intervals are appropriate for an individual patient. An influence of pharmacokinetics of BPs on antiresorptive action may contribute to this variation in response. To test this hypothesis, we determined the skeletal retention of intravenous pamidronate and its association to the rate of bone resorption in patients with bone metastases from breast cancer. MATERIALS AND METHODS: In a cross-sectional study, 24-h urinary excretion of pamidronate and the biochemical marker of bone resorption N-terminal telopeptide of type 1 collagen and serum alkaline phosphatase were measured in 40 patients with bone metastases from breast cancer at the beginning, after 3-6 months, and after 1 year of treatment with intravenous pamidronate 90 mg every 3-4 weeks. RESULTS AND CONCLUSIONS: Skeletal retention (dose--amount excreted into urine) 2 days after infusion varied between 12% and 98% (mean, 62%) of the administered dose, but there were no differences in retention between patients receiving pamidronate for the first time or after 3-6 months or after 1 year of treatment. Retention of pamidronate was related to the prevalent rate of bone turnover in previously untreated patients, whereas no such relationship was found in previously treated patients. Rate of bone resorption after treatment seemed to be related to the amount of pamidronate retained. During 1 year of treatment, retention of pamidronate remained constant, indicating no saturation of skeletal binding sites with treatment. The variability in retention among individual patients can be attributed to the number of available binding sites. This is related, however, to bone turnover only before the start of treatment. The apparent relationships between skeletal retention and antiresorptive effect could have implications for the design of optimal therapeutic regimens with BPs in patients with bone metastases from breast cancer.