对1例乳腺癌患者使用唑来膦酸的药学监护

1例65岁女性患者,因“左乳癌根治术后3年,多发转移19月余”入院。给予口服卡培他滨和拉帕替尼进行化疗,化疗期间加用唑来膦酸抗骨转移治疗。临床药师针对化疗过程中唑来膦酸可能出现的不良反应的预防和药物的合理性应用作为药学监护点,建议医生调整唑来膦酸的给药时间以提高抑制骨转移的疗效,从而使患者能顺利完成化疗。     

Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid

Background

Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear.

Objective

To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database.

Design, setting, and participants

Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n = 643) randomized to ZOL or placebo every 3 wk.

Outcome measurements and statistical analysis

PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point.

Results and limitations

A total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p < 0.0001) and 10% (p < 0.0074), respectively, for BDP, and 24% (p = 0.0010) and 13% (p = 0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies.

Conclusions

PSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy.     

唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床思路总结

目的 探讨唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移的临床效果.方法 选取我院于2011年7月至2013年7月收治的42例晚期非小细胞肺癌骨转移患者作为研究对象,按照随机分组方式将患者分为观察组21例和对照组21例,对照组给予常规化疗措施,观察组在化疗基础上给予唑来膦酸治疗,对两组患者NRS、KPS水平进行测评,评价两种治疗方式的效果.结果 观察组骨转移灶完全缓解7例,部分缓解9例,稳定4例,恶化1例,综合有效率（完全缓解＋部分缓解）为76.19％,对照组完全缓解4例,部分缓解3例,稳定5例,恶化9例,综合有效率为33.33％,两组患者综合有效率对比具有显著的统计学差异（P＜0.01）;两组患者经治疗后NRS、KPS均有不同程度改善,相比治疗前差异有统计学意义（P＜0.05）,观察组改善更为明显,相比对照组差异有统计学意义（P＜0.05）.结论 唑来膦酸联合化疗治疗晚期非小细胞肺癌骨转移疗效显著,对于缓解患者疼痛、改善患者预后具有重要的临床意义.     

静脉应用唑来膦酸注射液的临床安全性

目的分析唑来膦酸注射液应用的安全性。方法采用回顾性研究方法,对我院2010年1月至2014年1月使用唑来膦酸注射液的710例患者的药物不良反应进行统计分析。结果唑来膦酸注射液的不良反应以发热最常见,发生率为95.07%,其次是低血钙、低血磷。全部不良反应均为一过性反应,无严重不良反应发生。结论唑来膦酸的不良反应发生率高,应积极给予退热治疗,并及时给予血钙、磷、钾、镁、铁、肌酐及血常规监测,以确保不良反应的平稳过渡。     

唑来膦酸在骨质疏松性椎体压缩骨折经皮椎体成形术后的临床应用

目的：通过对比研究,观察骨质疏松性椎体压缩骨折的患者在经皮椎体成形术后应用唑来膦酸的临床治疗效果。方法2010年7月至2013年2月,将中山市中医院骨一科240例椎体压缩性骨折行PVP手术治疗的患者随机分成两组,治疗组在术后3日予以静滴唑来膦酸针;对照组单纯予以椎体成形术。两组患者自入院起均予以口服碳酸钙／维生素D3片,600 mg／d。分别于术前1周及术后1月、3月、6月、9月、一年行腰椎骨密度、血清PINP及β－CTX浓度检查,并进行统计分析。结果随访1年,两组患者共240例获得随访,治疗后治疗组患者在VAS评分、腰椎骨密度、血清PINP及β－CTX浓度等的变化与对照组相比均具有显著性差异,且治疗组患者的依从性较好,新发椎体骨折少。结论唑来膦酸治疗骨质疏松性椎体压缩骨折可增加患者椎体骨密度、改善患者疼痛、预防新发椎体骨折、提高患者生活质量,可用于骨质疏松性椎体压缩骨折患者PVP术后的巩固治疗。     

Efficacy of systemic bisphosphonate delivery on osseointegration of implants under osteoporotic conditions: Lessons from animal studies

Background

The aim was to systematically review the role of systemic bisphosphonate (BP) delivery on osseointegration of implants under osteoporotic conditions.

Methods

The addressed focused question was “Does systemic BP delivery enhance osseointegration of implants under osteoporotic conditions?” PubMed/MEDLINE and Google-Scholar databases were searched from 1994 up to and including December 2013 using different combinations of the following keywords: “bone to implant contact”, “implant”, “bisphosphonate”, “osseointegration” and “osteoporosis”. Review articles, case-reports, commentaries, letters to the Editor, unpublished articles and articles published in languages other than English were excluded.

Results

Fifteen animal studies fulfilled our eligibility criteria. Osteoporotic conditions were induced via bilateral ovariectomy (OVX). BPs used in the studies were ibandronate, zoledronic acid and alendronate. Results from 12 studies showed that systemic BP delivery significantly increased bone volume and bone-to-implant contact under osteoporotic conditions. Two studies reported no significant difference in osseointegration among OVX animals with and without systemic BP delivery. In one study, systemic BP delivery negatively influenced implant osseointegration. Rough-surfaced and polished implants were used in 11 and one study respectively. In 3 studies implant surface characteristics remained unclear.

Conclusion

Within the limits of the present study, it is concluded that systemic BP delivery enhances implant osseointegration in animals with induced osteoporotic conditions. However, in a clinical scenario, the potential risk of BP related ONJ in osteoporotic patients undergoing dental implant therapy cannot be disregarded.     

Sertaconazole: In-Vitro Antifungal Activity Against Vaginal and Other Superficial Yeast Isolates

Abstract

The in vitro susceptibilities of 183 clinical yeast isolates to sertaconazole (STZ) were compared to their susceptibilities to clotrimazole (CTZ), econazole (ECZ), ketoconazole (KTZ), miconazole (MNZ), fluconazole (FLZ), itraconazole (ITZ), tioconazole (TCZ), amphotericin B (AMB) and flucytosine (5FC) by using a commercial agar diffusion method. Strains were isolated from vaginal and other superficial clinical samples (18 species of Candida and five strains belonging to other yeast genera). Only one strain (0.5%) was resistant to STZ out of 87.4% of susceptible strains (n=160). The percentage of susceptible strains was higher than those obtained with the other agents evaluated and the percentage of resistant strains was lower than for most of the other antifun-gals. The pattern of susceptibility of C. albicans to STZ, TCZ, ITZ and CLZ was similar and superior to the pattern of susceptibility of this species to MNZ, ECZ, FLZ, 5FC and KTZ. C. dubliniensis was more susceptible to STZ, MNZ, MNZ, FLZ, ITZ, CLZ than to TCZ, ECZ, 5FC, AMB or KTZ. Ten susceptible strains to STZ were resistant to FLZ and one strain was resistant to ITZ. The overall antifungal activity of STZ in vitro against a wide range of clinically important yeasts from vaginal and cutaneous samples indicates the therapeutic potential of this agent for the treatment of infections caused by these fungi. However, the activity of STZ and the clinical value of in vitro data need to be verified in human clinical trials.     

唑来膦酸治疗实体瘤骨转移或多发性骨髓瘤中重度骨痛的Ⅲ期临床研究

目的 评价唑来膦酸治疗实体瘤骨转移或多发性骨髓瘤引起的中重度骨痛的效果和安全性.方法 采用随机、双盲、双模拟、多中心的实验设计方法.将228例实体瘤骨转移或多发性骨髓瘤引起中重度骨痛[视觉模拟评分(VAS)＞50 mm]的患者随机分为唑来膦酸组(116例)和帕米膦酸二钠组(112例),分别接受静脉输注唑来膦酸(4 mg)或帕米膦酸二钠(90 mg)的单剂量治疗.检测唑来膦酸对疼痛及尿液中I型胶原交联氨基末端肽(NTX)/肌酐(Cr)、Ⅰ型胶原交联羧基末端肽(CTX)/Cr的影响,并观察不良反应,评价其安全性.结果 228例患者中202例完成试验,其中唑来膦酸组104例,膦酸二钠组98例.用药后两组VAS评分逐渐下降,唑来膦酸组第8、15、22、28天对基线的平均变化百分比分别为-11.77%、-24.60%、-28.50%和-32.37%,帕米膦酸二钠组则分别为-10.87%、-21.06%、-25.67%和-31.26%,两组各时间点相对基线变化的百分比均有统计学意义(均P≤0.0001),但两组间相对基线变化的百分比差异无统计学意义(P=0.6587).用药后两组尿NTX/Cr均快速下降,第8天降到最低点,与基线相比,唑来膦酸组用药后第28天的变化百分比中位值为-36.9%(P=0.0002),帕米膦酸二钠为-32.1%(P=0.0018),两组问差异无统计学意义(P=0.7922).用药后两组尿CTX/Cr均快速下降,第8天时降到最低点,与基线相比,唑来膦酸组用药后第28天变化百分比中位值为-63.2%(P＜0.0001),帕米膦酸二钠组为-47.9%(P＜0.0001),两组间差异无统计学意义(P=0.834).唑来膦酸和帕米膦酸二钠组中常见的不良反应为发热(19.0%和31.3%)、呕吐(6.0%和8.9%)、恶心(4.3%和4.5%)、乏力(3.4%和2.7%)、便秘(2.6%和1.8%)、低钙血症(5.2%和3.6%),均未出现血肌酐值升高.结论 4 mg唑来膦酸单剂量治疗中国人实体瘤骨转移或多发性骨髓瘤,在缓解骨痛和降低骨吸收标记物方面与帕米膦酸二钠同样有效,患者耐受性好.     

唑来膦酸联合放疗治疗骨转移癌的临床疗效观察

目的 探讨唑来膦酸联合局部放疗治疗恶性肿瘤局限件骨转移的临床疗效.方法 45例局限性骨转移患者随机分为2组,联合治疗组23例,采用唑来膦酸静脉滴注加局部放疗;单纯放疗组22例,只采用局部放疗.结果 联合治疗组和单纯放疗组的疼痛缓解率分别为91.3%和86.4%.差异无统计学意义(P>0.05);联合治疗组和单纯放疗组的溶骨病灶再钙化的有效率分别为52.2%和22.7%,差异有统计学意义(P<0.01);联合治疗组和单纯放疗组出现新的骨转移病灶的患者比例分别为13.0%和40.9%,联合治疗组显著低于单纯化疗组(P<0.05).联合治疗组的不良反应主要为短暂低热和恶心.结论 唑来膦酸联合放疗治疗恶性肿瘤局限性骨转移疗效确切,其控制骨痛作用强,可高效修复溶骨病灶,并能降低新的骨转移灶发生率.     

唑来膦酸诱导Bel-7402人肝癌细胞分化的研究

目的探讨唑来膦酸诱导Bel-7402人肝癌细胞分化作用,为肝癌的分化治疗提供可借鉴的资料.方法选用反映肝细胞恶变的甲胎蛋白（AFP）的分泌量、γ-谷氨酰转肽酶（γ-GT）和醛缩酶（ALD）,反映肝癌细胞分化的酶学指标酪氨酸-α-酮戊二酸转氨酶（TAT）,鸟氨酸氨基甲酰转移酶（OCT）和碱性磷酸酶（ALP）作为观察肝癌细胞恶性表型逆转的指标.结果Bel-7402人肝癌细胞经0.05ug/ml唑来膦酸处理后,AFP分泌量明显低于对照组,γ-GT和ALD活力也明显低于对照组;相反,OCT、TAT和ALP的活力则明显高于对照组,差异均有显著意义（P＜0.05或P＜0.01）.结论证明唑来膦酸是体外培养Bel-7402人肝癌细胞有效的分化诱导剂.