晚期食管癌患者药物治疗方案的应用与评价

目的 评价我院晚期食管癌患者药物治疗方案中依从指南用药和未依从指南用药的有效性、安全性、经济性，为规范临床晚期食管癌患者诊疗提供依据。方法 将135例住院晚期食管癌患者分为依从指南组（60例）和未依从指南组（75例），比较两组的抗肿瘤药物平均相对剂量强度；根据实体瘤疗效评价标准和常见不良事件评价标准比较抗肿瘤药物治疗方案的疗效及安全性；统计患者的住院费用、药品费用和抗肿瘤药物费用，比较抗肿瘤药物治疗方案的经济性。结果 未依从指南组患者的平均相对剂量强度、客观缓解率、疾病控制率和药品不良反应发生率均高于依从指南组，但差异无统计学意义（P> 0.05）。未依从指南组患者的住院费用、药品费用和抗肿瘤药物费用均显著高于依从指南组（P <0.001）。结论 与未依从指南者比较，晚期食管癌患者药物治疗方案依从指南者的安全性和有效性可能无明显差异，但经济性较优。     

追踪评价新型抗肿瘤药物用药的适宜性、有效性和安全性

目的 追踪评价新型抗肿瘤药物用药的适宜性、有效性和安全性，完善药品供应，保障患者用药的可及性和连续性，促进临床合理用药经验的积累。方法 参考药品使用说明书建立新型抗肿瘤药物用前适应证审核标准；参考《新型抗肿瘤药物临床应用指导原则》和药品说明书建立追踪评价标准；采用追踪方法学评价实施新型抗肿瘤药物用前审核制度以来通过审核的患者用药的适宜性、有效性和安全性。结果 2018年度共审核通过41例新型抗肿瘤药物用药患者，适宜性评价结果为3例不符合用药指征，2例不符合给药方法。有效性评价结果为客观有效率53.7%（22/41），疾病控制率80.5%（33/41）；追踪时间截至2020年5月，24例无进展生存期>12个月，占比58.5%（24/41），14例患者死亡，占比34.1%（14/41）。安全性评价结果为7例使用贝伐珠单抗未检测尿常规，4例使用曲妥珠单抗未检查心脏超声；可能由新型抗肿瘤药物引起的不良反应，包括4例使用曲妥珠单抗发生心脏不良反应，2例使用索拉菲尼或奥西替尼发生皮肤及皮下组织不良反应，1例使用贝伐珠单抗发生出血不良反应，不良反应发生率17.1%（7/41）。结论 实施新型抗肿瘤药物用前审核制度可以保障患者用药的可及性和连续性，临床药师应积极实施新型抗肿瘤药物的药物重整、药学监护和用药教育，提高患者用药的适宜性、有效性和安全性。     

老药新用抗肿瘤作用的研究进展

化学药物治疗是肿瘤治疗的传统方法之一,在肿瘤治疗中占有重要的地位。目前,临床常用的抗肿瘤药物存在疗效欠佳,毒副作用大等缺点,而研发新的抗肿瘤药物具有耗时长、投入大等问题。近年来有研究发现,大量临床安全性明确且已被广泛应用于临床的非抗肿瘤药物也可能具有抗肿瘤作用,如黄芪、雷公藤、二甲双胍、阿司匹林等,并对其进行了深入的研究。本文将对这些非抗肿瘤药物抗肿瘤作用的研究进展作一综述。     

我院2000～2004年抗肿瘤药使用分析与趋势

目的:对我院抗肿瘤药物用药的现状和趋势做出评价。方法:对我院2000~2004年抗肿瘤药物进行回顾性分析。结果:抗肿瘤药销售金额逐年上升;抗肿瘤辅助治疗药格拉司琼连续5年销售金额名列第一;5年中抗雌激素类抗肿瘤药他莫昔芬用药频度排名稳居榜首,其他类抗肿瘤药顺铂位居第二;国产药物销售金额始终最大;医保类药物具有较高使用率。结论:我院抗肿瘤药物结构基本合理;推广和使用国产药物,利于降低药品费用。     

抗肿瘤药物肝损伤研究进展

本文对抗肿瘤药物肝损伤的危险因素、诊断标准和临床分型、特异性易感基因检测的研究现状进行归纳,同时结合自身研究成果,总结抗肿瘤药肝损伤的防治措施,提出建设抗肿瘤药物肝损伤分子检测与临床评价技术平台,将对预测药物肝损伤的发生、指导临床化疗药物使用和新型药物开发具有重要的意义。     

抗肿瘤药物不良反应报告84例分析

目的了解我院抗肿瘤药物不良反应（ADR）发生的特点及规律,为临床安全用药提供参考。方法采用回顾性分析研究方法,对我院2008年至2010年上报的84例抗肿瘤药物ADR报告进行统计、分析与评价。结果 84例ADR中,男39例,女45例;50岁以上中老年患者较多,占60.71%;涉及抗肿瘤药物7大类、52种,抗肿瘤植物药的ADR发生频率排首位;变态反应43例和消化系统反应27例,分别占36.13%和22.69%。结论应加强对肿瘤患者ADR的监测工作,以保证用药安全性。     

《中国执业药师》杂志2011年专栏征稿通知

为提高《中国执业药师》杂志稿件的学术水平,为广大药学工作者提供一个展示、交流的平台,本刊2011年将组织如下专栏。抗菌药物的合理应用与安全性评价;抗肿瘤药物的研发与应用;临床药学监护;儿科药物的研发与应用;内分泌与     

《中国执业药师》杂志2012年专栏征稿通知

为提高《中国执业药师》杂志稿件的学术水平,为广大药学工作者提供一个展示、交流的平台,本刊2012年将组织如下专栏。抗菌药物的合理应用与安全性评价;抗肿瘤药物的研发与应用;临床药学监护;儿科药物的研发与应用;内分泌     

《中国执业药师》杂志2012年专栏征稿通知

为提高《中国执业药师》杂志稿件的学术水平,为广大药学工作者提供一个展示、交流的平台,本刊2012年将组织如下专栏。抗菌药物的合理应用与安全性评价;抗肿瘤药物的研发与应用;临床药学监护;儿科药物的研发与应用;内分泌     

纳米粒作为抗肿瘤药物载体的研究进展

近年来纳米粒作为抗肿瘤药物载体的制备、作用机制及其体内外药效学评价等方面取得较大的进展.纳米粒作为抗肿瘤药物的载体具有许多优点,并可通过多种方式提高所携药物的药效学特征,显示纳米粒在肿瘤治疗领域具有广泛的应用前景.     

Neovastat--a novel antiangiogenic drug for cancer therapy

Neovastat (AE-941) is an antiangiogenic drug isolated from marine cartilage. It interferes with several steps associated with the development of angiogenesis through its ability to induce endothelial cell apoptosis, and to inhibit matrix metalloproteinase activities and vascular endothelial growth factor-mediated signaling pathways, suggesting that Neovastat behaves as a multifunctional antiangiogenic drug. Neovastat is orally bioavailable, and shows significant antitumor and antimetastatic properties in animal models. An excellent safety profile with few side effects has been monitored in more than 800 patients who have been exposed to Neovastat, some of whom for more than 4 years. This indicates that Neovastat is suitable for long-term use, either alone or in combination with other anticancer therapies. Accordingly, Neovastat is currently under evaluation in three pivotal clinical studies with two phase III clinical trials in patients with lung and renal carcinoma, and a phase II clinical trial in patients with multiple myeloma is ongoing.     

Immune reconstitution inflammatory syndrome associated with bacterial infections

Drug safety of atypical antipsychotics is important due to the increasing mortality gap between patients with schizophrenia and the general population. This editorial discusses the safety evaluation of ziprasidone with a focus on the risk of the potentially fatal cardiac arrhythmia, torsades de pointes (TdP). The exact incidence of antipsychotic-induced TdP remains unknown because capturing TdP warrants continuous monitoring and tens of thousands of patient-years due to the rarity of TdP. For this reason, surrogate markers such as the QTc interval are used despite their limitations. New surrogate markers Tpeak-Tend and T-wave morphology have seen the light of day but their validity remain unknown. Large pragmatic trials have been conducted, but their contributions to drug safety evaluations are controversial. Finally, psychiatrists should have in mind that safety evaluation should include more than the risk of TdP. Some atypical antipsychotics are associated with life-shortening side effects, such as severe weight gain and type 2 diabetes, which may contribute more to the overall mortality than TdP. In addition to this, suboptimal treatment may result in life-shortening behaviors such as suicide. A shared decision including a thorough discussion of risks and benefits with the patients is essential.     

The safety of atypical antipsychotics: does QTc provide all the answers?

Drug safety of atypical antipsychotics is important due to the increasing mortality gap between patients with schizophrenia and the general population. This editorial discusses the safety evaluation of ziprasidone with a focus on the risk of the potentially fatal cardiac arrhythmia, torsades de pointes (TdP). The exact incidence of antipsychotic-induced TdP remains unknown because capturing TdP warrants continuous monitoring and tens of thousands of patient-years due to the rarity of TdP. For this reason, surrogate markers such as the QTc interval are used despite their limitations. New surrogate markers Tpeak-Tend and T-wave morphology have seen the light of day but their validity remain unknown. Large pragmatic trials have been conducted, but their contributions to drug safety evaluations are controversial. Finally, psychiatrists should have in mind that safety evaluation should include more than the risk of TdP. Some atypical antipsychotics are associated with life-shortening side effects, such as severe weight gain and type 2 diabetes, which may contribute more to the overall mortality than TdP. In addition to this, suboptimal treatment may result in life-shortening behaviors such as suicide. A shared decision including a thorough discussion of risks and benefits with the patients is essential.     

新药研发中毒理学研究方法的进展--非临床安全性评价的新工具

近年来在新药非临床安全性评价中越来越多采用新方法和新技术，以适应不同特点新药的开发和使安全性评价更具预测性。现综述国外近几年在非临床安全性评价中采用的新工具，包括生物标记物，以及毒理基因组学、毒理蛋白质组学、代谢组学和系统毒理学方面的新技术。     

Aerosolized chemotherapy

Regional chemotherapy has been proposed as a treatment modality in a number of cancer settings. In primary or metastatic lung cancer, administration of chemotherapy via inhalation could increase exposure of lung tumor to the drug, while minimizing systemic side effects. Several proof of concept studies in animal models of metastatic or primary lung cancer have demonstrated the safety, pharmacokinetic advantage, and antitumor effect of aerosol administration of several chemotherapeutic agents including doxorubicin, gemcitabine and liposome-encapsulated formulations of paclitaxel and 9-nitrocamptothecin (9-NC). Recent phase I studies have demonstrated the feasibility of aerosol delivery of doxorubicin and liposomal formulations of 9-NC and cisplatin in patients with primary and metastatic lung cancer with a limited pharmacokinetic profile consistent with the observed low systemic toxicity. Further studies integrating safety, pharmacokinetic, and efficacy considerations are required to determine whether there is a place for local administration of chemotherapy via inhalation in lung cancer.     

pH敏感型纳米递药系统在肿瘤靶向治疗中的作用

目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。     

A regulatory perspective on issues and approaches in characterizing human metabolites

This document captures the current thinking within FDA/CDER on the non-clinical safety assessment of human drug metabolites in new drug products. Examples are provided, which define a scientific based approach to the safety evaluation of human metabolites in new drug candidates. A discussion of the need for, and the adequacy of, the assessment of human drug metabolites with specific regard to their potential as mediators of toxicity is presented from a regulatory perspective.     

Enhanced antitumor efficacy and decreased toxicity by self-associated docetaxel in phospholipid-based micelles

To overcome the poor aqueous solubility of docetaxel (DTX) and the side effects of the emulsifier in the marketed formulation, we have developed a DTX-loaded micelle using a nontoxic and biodegradable amphiphilic diblock copolymer, methoxy polyethylene glycol-distearoylphosphatidylethanolamine (mPEG(2000)-DSPE). The prepared micelles exhibited a core-shell structure, and DTX was successfully encapsulated in the core with an encapsulation efficiency of 97.31 ± 2.95% and a drug loading efficiency of 3.14 ± 0.13%. The micelles were spherical with a hydrodynamic diameter of approximately 20 nm, which could meet the requirement for in vivo administration, and were expected to enhance the drug's antitumor efficacy and to decrease its toxicity. To evaluate the DTX-loaded micelles, we chose a well marketed formulation, Taxotere(?), as the control. The prepared DTX micelle had a similar antiproliferative effect to Taxotere(?) in vitro but a significantly better antitumor efficacy than Taxotere(?) in vivo, which may be caused by passive targeting of the tumor by the micelles. In addition, the safety evaluation revealed that the DTX micelle was a qualified drug for use in vivo. Based on the experimental results, we propose that mPEG(2000)-DSPE micelle is a potent carrier for DTX.     

Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo

Pegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles and ultrasound (US) is a promising strategy for enhancing the antitumor effects of chemotherapeutics by improving drug delivery. Recently, several preclinical studies have shown the drug delivery potential of lipid bubbles (LBs), newly developed monolayer microbubbles, in combination with low-intensity US (LIUS). This study aimed to elucidate whether the combined use of LBs and LIUS enhanced the intratumoral accumulation and antitumor effect of PLD in syngeneic mouse tumor models. Contrast-enhanced US imaging using LBs showed a significant decrease in contrast enhancement after LIUS, indicating that LIUS exposure induced the destruction of LBs in the tumor tissue. A quantitative evaluation revealed that the combined use of LBs and LIUS improved the intratumoral accumulation of PLD. Furthermore, tumor growth was inhibited by combined treatment with PLD, LBs, and LIUS. Therefore, the combined use of LBs and LIUS enhanced the antitumor effect of PLD by increasing its accumulation in the tumor tissue. In conclusion, the present study provides important evidence that the combination of LBs and LIUS is an effective method for enhancing the intratumoral delivery and antitumor effect of PLD in vivo.