卵巢癌的治疗药物研究进展

卵巢癌是女性生殖器官常见的恶性肿瘤之一,其死亡率居妇科恶性肿瘤首位,且发病率逐年增加。全球新批准并上市的治疗卵巢癌的药物有贝伐单抗、曲贝替定、人参皂苷以及一些新制剂,处于研发后期的抗卵巢癌药物有奥拉帕尼、西地尼布、nintedanib、trebananib以及一些抗卵巢癌药的新剂型品种等。对近年来上市和处于研发后期的卵巢癌的治疗药物进行了详细介绍,同时对抗卵巢癌药的未来发展方向进行了展望,以期为抗卵巢癌药物的研发提供参考。     

临床研究获得阳性结果的三种药物——用于转移性黑色素瘤患者的Avastin

一项由214名患者参加的大型、随机、名为BEAM的Ⅱ期临床试验中，由罗氏（基因泰克）开发的Avastin（贝伐单抗）显示出可改善转移性黑色素瘤患者的总生存期（OS）、无进展生存期（PFS）和应答率的趋势，为这种大多数治疗均已无能为力且中位生存期不超过1年的顽疾的治疗带来了希望。     

非小细胞肺癌新靶向药物治疗研究进展

非小细胞肺癌(NSCLC)是一种常见的恶性肿瘤,尽管化学治疗适度提高了晚期NSCLC病人的生存率,但总体来说预后仍不乐观。而分子靶向药物治疗具有符合生理、低毒和理论上高效的特点,已越来越成为晚期NSCLC治疗的热点。以肿瘤血管生成为靶点的血管内皮生长因子拮抗药贝伐单抗和抗肿瘤血管生成靶向药物血管内皮抑素显示出明显生存优势;以表皮生长因子受体为靶点的酪氨酸激酶抑制药吉非替尼、厄洛替尼和多激酶抑制药索拉非尼,不良反应少、易耐受、疗效高,显示出较好的应用前景。     

用于转移性黑色素瘤患者的Avastin

一项由214名患者参加的大型、随机、名为BEAM的Ⅱ期临床试验中,由罗氏(基因泰克)开发的Avastin(贝伐单抗)显示出可改善转移性黑色素瘤患者的总生存期(OS)、无进展生存期(PFS)和应答率的趋势,为这种大多数治疗均已无能为力且中位生存期不超过1年的顽疾的治疗带来了希望.     

恶性黑色素瘤的分子靶向药物治疗研究进展

恶性黑色素瘤(MM)是预后不良的疾病.转移性MM现可用的全身治疗、化疗和免疫治疗,有效率低,有效持续时间短,5年生存率<10%,急需有效的新治疗方法.细胞毒T-淋巴细胞抗原-4(CTLA-4)抗体——易普利单抗(ipilimumab)和tremelimumab已在临床上研究,经严格的Ⅲ期试验对曾治的转移性MM与对照组比较,ipilimumab有延长总生存期益处.威罗菲尼(Vemurafenib,PLX4032)是癌基因BRAF激酶抑制剂,对未曾治疗有BRAF(V600E)突变的MM患者有很高的有效率,且能延长无进展生存期和总生存期.因此,美国食品药品管理局(FDA)先后批准应用ipilimumab和vemurafenib治疗晚期MM患者.临床试验化疗或靶向药联合应用可能更有益.其他靶向药物,包括血管生成和雷帕霉素靶蛋白抑制剂正在研究.     

甲磺酸伊马替尼致黄疸

患者女,51岁,既往无药物过敏史及其他疾病史。于2003年发现白细胞增高,2004年无明显诱因出现乏力,偶伴头晕,2006年症状加重。2006年8月4日来院,查WBC     

甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果分析

目的 探讨甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果.方法 选择我院2008年5月至2011年5月慢性粒细胞白血病患者共50例,以上患者随机分为观察组和对照组.两组患者均根据具体临床分期等情况给予不同化疗方案.观察组给予甲磺酸伊马替尼治疗.评定两组患者治疗效果,记录两组不良反应发生情况.结果 观察组缓解率为96.0%,对照组缓解率为76.0%,观察组缓解率与对照组比较,差异有统计学意义(P<0.05);观察组恶心呕吐发生率、下肢浮肿发生率、皮疹发生率、肝功能异常发生率分别与对照组比较,差异有统计学意义(P<0.05).结论 甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果显著,治疗过程中不良反应发生率低,值得借鉴.     

甲磺酸伊马替尼治疗高危胃肠间质瘤预后的研究

目的探讨靶向药物甲磺酸伊马替尼对高危胃肠间质瘤(GIST)患者预后的影响。方法回顾性分析2008年1月~2013年5月手术治疗的97例原发高危GIST患者的临床病理及术后随访资料。结果 97例患者中男性51例,女性46例,平均年龄57岁。肿瘤位于小肠(45.3%)、胃(42.3%)、结直肠(12.4%)。其中术后随访89例,中位随访时间33(6~96)个月,复发率43.8%(39例),死亡率20.2%(18例)。1,3和5年生存率分别为94.1%,83.2%和64.3%。术后43例服用甲磺酸伊马替尼,中位时间为28(9~74)个月。单因素和多因素预后分析显示,术后是否服用甲磺酸伊马替尼辅助治疗是影响预后的独立危险因素(P<0.05)。结论术后给予靶向药物甲磺酸伊马替尼辅助治疗可明显改善原发高危GIST患者的预后。     

离子色谱法测定甲磺酸伊马替尼中甲磺酸

目的 建立离子色谱法测定甲磺酸伊马替尼中甲磺酸的检测方法.方法 采用IonPac AS11-HC阴离子分析柱(250mm×4.0 mm),柱温30℃,电导检测器,进样量10μL,淋洗液为10 mmol/L氢氧化钾溶液,体积流量1mL/min,采集时间10min.结果 甲磺酸在38.5～192.6 μg/mL线性关系良好(r=0.999 7),准确度的RSD为0.23％.结论 本法准确、可靠,可作为甲磺酸伊马替尼中甲磺酸的测定方法.     

胃肠道间质瘤诊断与治疗的临床研究

目的：分析胃肠道间质瘤临床常用的诊断与治疗方法,并对其方法的有效性、安全性进行研究。方法：选择2005年1月～2010年1月在本院进行了手术治疗的胃肠道间质瘤患者共65例作为治疗组,随机选择同一时段86例胃、结直肠癌患者做为对照组,比较分析治疗组与对照组的CT、消化道造影、内镜＋活检资料的临床价值。将该组胃肠道间质瘤患者按照手术后是否服用甲磺酸伊马替尼分为两组,治疗组：手术＋甲磺酸伊马替尼,对照组：手术。分析二者在疗效上的差异。结果：CT、消化道造影、内镜＋活检等临床资料显示出能够帮助诊断的显著性的差异。是否服用甲磺酸伊马替尼在复发、转移、生存时间等方面具有显著性差异。结论：临床资料不能确诊胃肠道间质瘤,但能够提供相当准确的临床诊断;GIST术后复发率很高,甲磺酸伊马替尼对防止转移、复发、延长生存时间有良好的疗效。     

Protein kinase inhibitors in melanoma

Introduction: The most commonly mutated oncogene identified to date in melanoma is BRAF (～ 50%), an upstream mediator of the mitogen-activated protein kinase (MAPK) pathway. Recently, BRAF-kinase inhibitors as well as MEK-kinase inhibitors were introduced into the clinics.

Areas covered: Substantial Phase II and III clinical trials were searched in patients with advanced melanoma treated with BRAF-kinase inhibitors, MEK-kinase inhibitors and cKIT inhibitors.

Expert opinion: For patients with a BRAF, NRAS or cKIT mutation the treatment with selective, targeted drugs is considered as feasible and results in a high rate of confirmed tumor responses. In patients with BRAF mutation the progression free survival and overall survival is prolonged in patients who were treated with BRAF kinase inhibitors or MEK kinase inhibitors compared to patients receiving chemotherapy with dacarbazine. A major problem is the development of resistance to the inhibitors through multiple different mechanisms. One approach to overcome resistance is to combine BRAF and MEK inhibitors. Treatments with kinase inhibitors are more efficacious than chemotherapies, however, they compete with the newly developed immune checkpoint blockers, and may in future be preferentially applied in second- or x-line.     

口服阿片类药物的滥用现状分析与建议

口服阿片类药物主要用于中、重度癌痛的治疗,随着使用人群不断增加,滥用问题日趋明显。口服类阿片药物滥用已成为国家药监部门重点关注问题。对典型口服阿片类药物羟考酮及其复方制剂、曲马多及其复方制剂、复方地芬诺酯片进行滥用和监管现状分析,从不同层面展开思考,并提出建议,以期为我国口服阿片类药物的监管和合理用药提供参考。     

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

Introduction: Gastrointestinal stromal tumor (GIST) is the most common nonepithelial malignancy of the GI tract. With the discovery of KIT and later platelet-derived growth factor α (PDGFRA) gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST.

Areas covered: This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans.

Expert opinion: It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival.     

抗逆转录病毒药物的现状与研发

获得性免疫缺陷综合征（AIDS）是威胁人类健康的最危险疾病之一,是由人免疫缺陷病毒（HIV-1）感染引起。从HIV-1病毒发现后的30余年,已有大量的抗逆转录病毒药物投入研发,抑制病毒复制增殖周期的关键阶段。抗逆转录病毒药物延长了患者生命,同时也产生了病毒的耐药变异,因此需要开发针对耐药的新药物。简述美国已上市的抗逆转录病毒药物信息,重点关注抗逆转录病毒药物的研发进展以及非临床研究中的相关问题。     

靶向抗肿瘤药物个体化用药的研究现状

随着靶向抗肿瘤药物在肿瘤治疗中地位日益提高,越来越多作用于不同靶点的药物在临床上应用;通过对药物生物标志物的研究来预测疗效和预后,对患者进行个体化治疗。本文对靶向抗肿瘤药物在个体化用药的现状和应用前景作一综述。     

The safety and efficacy of dabrafenib and trametinib for the treatment of melanoma

Introduction: The introduction of BRAF and MEK inhibitors into clinical practice improved the prognosis of metastatic melanoma patients. The combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown its superiority to single agent therapy and is characterized by a tolerable spectrum of adverse events which shows a decrease in incidence over time on treatment.

Areas covered: The current scientific literature on safety and adverse events (AEs) related to BRAF and MEK-inhibition has been investigated with special focus on the large phase 3 studies (COMBI-v, COMBI-d and CoBRIM) as well as recent updates presented at oncology and melanoma meetings. Additionally, published case series/case reports were screened for information on AEs.

Expert opinion: Even though almost every patient (98%) under combination therapy with dabrafenib and trametinib experiences at least one adverse event, these are generally mild to moderate, reversible and can be managed with dose reductions or interruptions. However, due to an increased life expectancy, there is a substantial need to prevent and treat also mild adverse events, as they play a central role for the quality of life of patients. Ongoing clinical trials will have to demonstrate the efficacy as well as safety of triple combination with anti-PD-1/anti-PD-L1 antibodies.     

芥子气损伤防治药物的研究进展

芥子气是典型的糜烂性毒剂,其主要损伤机制是与生物分子作用,形成烃化物。近年对芥子气损伤机制的研究集中在DNA烃化、DNA链断裂、聚(ADP-核糖)聚合酶(PARP)激活、钙紊乱、蛋白水解酶激活和炎症反应等方面,而防治药物的研究也相应地得到进一步扩展。本文综述了不同作用机制的抗芥子气损伤药物的研究进展。     

样本医院儿童用药现状分析

目的：调查研究样本医院儿童用药的基本情况以及重点药物的使用情况，分析可能的危险因素。方法：回顾分析样本医院2017年7月至2018年6月门诊及住院患者中1~14岁儿童的用药情况，进行分类、排序、汇总分析，结合说明书，判断其医嘱是否超说明书，并对重点药物进行进一步分析研究。结果：样本医院处方占比最多的药物依次是平喘类药物、头孢菌素以及维生素类药物，处方占比最高的20种药物总权重是72.98%，前20种药物中有19种药物说明书中明确规定了针对儿童的用法用量；注射用盐酸氨溴索有96.31%的患者用药频率为每天一次，100%的6岁以下儿童存在单次用药剂量过大问题，6~12岁患者中有52%的人存在剂量过大问题；阿奇霉素注射剂存在超说明书情况，但基本能做到对症使用，按需给药。结论：样本医院在儿童用药选择方面卓有成效，但在个别重点药物使用上存在超说明书使用现象，需要重点关注，并制定相关措施进行干预和保障。     

Successes and setbacks of early investigational drugs for melanoma

Treatment of advanced and metastatic melanoma is a rapidly changing field. Over the past 10 years, there have been six new drugs approved by the FDA for the treatment of metastatic melanoma. These approved drugs include a number of immune checkpoint inhibitors and MAPK-pathway-targeted therapies. The discovery of such agents as ipilimumab, pembrolizumab, nivolumab, vemurafenib, trametininb and dabrafenib have revolutionized the way in which melanoma in managed. While these agents have succeeded in both early and later phase clinical trials, a large number of investigational therapies have not yet been developed or researched past Phase I clinical studies. Furthermore, there are dozens of potential agents in Phase I and Phase II clinical development that appear promising and are currently being explored. The field currently aims to determine the optimal sequence and combination of these therapies to best overcome such setbacks as toxicity and resistance and build upon the successes previously seen.