联合用药进行抗肿瘤治疗的研究进展

近年来联合用药逐渐成为肿瘤治疗的研究热点,联合用药可以通过发挥药物的协同抗肿瘤作用,达到在减小化疗药物毒副作用的同时增加药物抗肿瘤效果的目的.本文综述了近年来联合用药用于肿瘤治疗的相关研究,包括:抗体-药物偶联物、多药耐药逆转剂联合抗肿瘤药、基因治疗联合抗肿瘤药以及光动力疗法联合抗肿瘤药,为联合用药的设计及应用提供参考.     

抗肿瘤药物的治疗药物监测研究

尽管治疗药物监测(TDM)已广泛应用于多个疾病治疗领域,但在抗肿瘤药物方面的应用仍较为局限。近年来,抗肿瘤药物的暴露量与其疗效和药物不良反应之间的相关性研究越来越多,这有利于抗肿瘤药物个体化精准给药。本文综述了细胞毒类和靶向性(小分子和大分子)抗肿瘤药物的治疗药物监测现状,为肿瘤药物个体化用药提供参考。     

包头肿瘤医院2008～2010 年抗肿瘤药物使用情况分析

目的分析包头肿瘤医院抗肿瘤药物应用情况,作出客观评估,为该类药物的临床应用提供参考。方法采用金额排序法和用药频度分析法对该院2008～2010年抗肿瘤药物的使用情况进行统计。结果按金额排序,中药、抗代谢药及抗肿瘤植物药是抗肿瘤治疗的主要用药,三类药物占总销售金额的近70%;用药频度排名前三位药品分别是他莫西芬、托瑞米芬、来曲唑,三种药物3年分别占总用药强度的47.8%、44.4%、50.1%。结论该院抗肿瘤药物用药金额与用药频度呈逐年上升趋势;肿瘤治疗应考虑疗效与经济成本等多种因素,优化治疗方案、实现个体化给药,从而提高肿瘤联合治疗效果,节约抗肿瘤药物资源。     

某三甲医院恶性肿瘤患者抗肿瘤药物静脉输液顺序的调查分析★

目的分析我院肿瘤内科2019年第4季度恶性肿瘤住院患者药物联合治疗输液顺序的合理性,为临床合理用药提供参考。方法制定抗肿瘤药物联合治疗静脉输液顺序合理性评价标准,提取我院肿瘤内科2019年第4季度接受药物联合治疗患者输液卡上治疗药物的输液时间,分析并评价药物联合治疗输液顺序的合理性。结果 2019年第4季度我院肿瘤内科接受药物联合治疗的患者共计215例次,涉及治疗方案37种。其中3种治疗方案输液顺序不合理,涉及患者10例次,占比12.7%。结论我院肿瘤内科2019年第4季度抗肿瘤药物联合治疗静脉输液顺序总体合理,但仍存在一些亟需改进的不合理之处,以进一步提高合理用药水平。     

广东地区42所医院抗肿瘤药利用分析

目的:评价广东省抗肿瘤药的使用情况及发展趋势.方法:采用金额排序法和频度分析法,统计分析广东省药学会入网医院2003～2006年抗肿瘤药利用情况.结果:抗肿瘤药销售金额呈逐年上升趋势,年平均增长率为17.56%;用药频度除抗肿瘤植物成分药有轻微下降外,其他各类呈上升趋势;抗肿瘤抗生素的日均费用最高;临床用药以国产药为主,销售金额占总金额的50%以上;他莫昔芬用药频度4年来稳居榜首,销售金额排在前10位的药物以植物成分抗肿瘤药居多,其次为其他抗肿瘤药及辅助治疗药.结论:广泛开展综合治疗、利用靶向治疗、完善支持治疗,从而提高肿瘤联合治疗效果,成为肿瘤治疗的新策略.     

DUR和DUE法评价恶性淋巴瘤患者的用药情况

目的评价我院恶性淋巴瘤(ML)患者的用药情况及合理性,为临床合理用药提供参考。方法采用药物利用评价(DUR)和药物利用评估(DUE)法,对2016年上半年出院的ML患者抗肿瘤药物的药物利用指数(DUI)、评价指标和诊断、治疗药物监测及临床治疗效果等进行综合性分析。结果纳入DUI分析的抗肿瘤药物共13种,3种药物DUI>1,1种药物DUI=1,9种药物DUI<1。化疗方案较多采用指南推荐的CHOP、RCHOP一线方案。用药频次前3位的是长春地辛、环磷酰胺和多柔比星,用药频度前3位的是环磷酰胺、长春地辛和多柔比星。74例ML患者均确定了临床分期,仅有52例确定了病理学分型。药品不良反应发生率最高的是胃肠道反应。71例(95.9%)患者经治疗后临床症状得到改善,60例(81.1%)患者浅表淋巴结肿块缩小。结论我院ML患者化疗用药基本合理,临床诊疗规范,应注意加强治疗过程监测。联合DUR和DUE法可以更全面地评价恶性淋巴瘤患者的用药情况。     

沙利度胺联合用药抗肿瘤研究进展

20世纪60年代沙利度胺因其具有致畸性而退出历史舞台,后来研究发现其致畸现象的背后是抗血管生成的作用。而抗血管生成作用这时已被学术界认为是对抗肿瘤生成的一个重要因素。后来,研究人员又发现了沙利度胺的其他抗肿瘤机制,这样沙利度胺便被作为一种极具潜力的抗肿瘤药物而被广泛研究。本文重点综述了沙利度胺的抗肿瘤作用机制以及它与其他药物联合用药用于治疗实体瘤的研究进展。     

住院患者抗肿瘤药物超说明书用药医嘱点评方法探讨与应用评价

目的: 建立住院患者抗肿瘤药物超说明书用药医嘱点评方法,并将其应用于抗肿瘤药物用药合理性综合评价。方法: 基于循证原则和文献方法,针对抗肿瘤药物使用过程中与超说明书应用相关的适应证、给药剂量、给药途径及给药顺序等主要指标建立了评价标准,这个评价标准还包含了抗肿瘤药物使用过程中其他合理用药的评价指标。依据建立的评价标准,随机抽取我院肿瘤内科住院患者2 050份病历,对抗肿瘤药物用药合理性进行综合评价,并根据点评结果积极干预临床用药。结果: 点评结果显示,抗肿瘤药物的超说明书用药情况主要体现在化疗剂量不准确、给药途径不符合说明书规定或序贯给药顺序不恰当,未发现不符合适应证应用的情况;干预后,化疗剂量和给药顺序等超说明书用药相关指标得到明显改善。结论: 建立了以超说明书用药为主要评价内容的抗肿瘤药物医嘱点评方法,制定的评价标准和调查表能够方便临床药师全面深入判断抗肿瘤药物在超说明书用药环节存在的问题,为进一步开展相关研究提供思路。     

钙通道阻滞剂与心血管药物的相互作用

近年来钙阻滞剂在临床上的应用日趋广泛,特别在心血管疾病的治疗中占有重要地位。为了提高疗效常与其它心血管药物联合使用,尤其是与地高辛、β阻滞剂合用较多,有的产生协同作用,有的可使毒、副作用增加。本文综述有关资料以供临床用药时参考。     

我院抗肿瘤中成药利用分析

目的促进医院抗肿瘤中成药安全、合理地使用。方法采用推荐的限定日剂量(DDD)和药物利用指数(DUI)作为药物利用研究和评价单位,统计抗肿瘤中成药的名称、医保类别、总金额、用药频度(DDDs),并统计分析。结果药物金额排序以中成药注射剂用量较大,医保乙类的药物使用最多;用药频度排序中,口服中成药制剂居前。口服制剂的药物治疗指数偏高,可能存在不合理应用,注射剂的DUI较合理。结论抗肿瘤中成药注射剂使用基本合理。     

An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human glioma cells

Transferrin receptor (TfR) has been used as a target for antibody-based therapy of cancer. Anti-TfR antibody together with chemotherapeutic drugs has potential for cancer therapy. In this study, we investigated the in vitro anti-tumor effects of the anti-TfR monoclonal antibody (mAb), 7579, alone or in combination with Nimustine, a chemotherapeutic drug, on the gliomas cell lines U251 and U87MG. Our results indicated that 7579 alone dramatically down-regulated surface expression of TfR on tumor cells and induced S phase accumulation and apoptosis of tumor cells. Compared with 7579 or Nimustine used alone, the combination of 7579 with Nimustine demonstrated enhanced growth inhibitory effect on tumor cells. PI (Propidium iodide)/Annexin V staining analyzed by FCM (flow cytometry) demonstrated that 7579 enhanced the cytotoxic effects of chemotherapeutic drug on tumor cells, indicating the therapeutic effect of 7579 was mediated mainly by promoting tumor cell necrosis. Using the median-effect/combination-index isobologram method, we further evaluated the nature of 7579/chemotherapeutic drug interactions. Synergistic interaction was observed for combination of 7579 with Nimustine. Our study provides additional evidence to develop combination therapies of anti-TfR mAbs-plus chemoimmunotherapy for gliomas.     

水凝胶在肿瘤免疫治疗中的研究进展

近年来,免疫疗法在癌症治疗领域受到了极大的关注,联合治疗已经产生了良好的临床治疗效果。然而,患者对免疫治疗的反应率仍然不高,这需要注意肿瘤部位的药物利用率和全身性副作用。水凝胶作为载药平台具有极大的优点,可将抗肿瘤药物直接递送至肿瘤部位,降低全身毒性,并具有良好的可降解性。本篇综述报道了基于水凝胶平台的药物输送系统的新进展,包括免疫化学治疗、免疫放疗和免疫光热治疗等多种免疫治疗联合治疗。     

Thermosensitive porphyrin-incorporated hydrogel with four-arm PEG-PCL copolymer (II): doxorubicin loaded hydrogel as a dual fluorescent drug delivery system for simultaneous imaging tracking in vivo

Visualization of a drug delivery system could reveal the pharmacokinetic properties, which is essential for the design of a novel drug delivery system. In vivo optical imaging offers an advanced tool to monitor the drug release process and the therapeutic effect by the combination of fluorescence imaging and bioluminescence imaging. Multispectral fluorescence imaging can separate the drug and the carrier without interference. Herein, a dual fluorescent anti-tumor drug delivery system was monitored with the doxorubicin-loaded hydrogel to further explore the application of the porphyrin-incorporated hydrogel with four-arm PEG-PCL copolymer as a drug carrier, based on the beneficial fluorescence and good biocompatibility of the porphyrin incorporated hydrogel. Using nude mice bearing luciferase expressed hepatic tumor as models, the whole process from the drug delivery to the tumor therapeutic effects were real time visualized simultaneously after administration at interval from 0 to 18 d. The imaging results suggest that the fluorescence signals of the drug and the carrier can be separated and unmixed from the drug-loaded hydrogel successfully, avoiding the interference of the fluorescence signals. The tumor growth or inhibition can be real time tracked and analyzed quantitatively by bioluminescence imaging. Noninvasive continuous tracking the in vivo drug delivery process simultaneously is a potential trend for the precise drug delivery and treatment.     

Immunotherapy with tumor-targeted superantigens (TTS) in combination with docetaxel results in synergistic anti-tumor effects

In this study we explored the possibility of combining immunotherapy against cancer with the well-established cytostatic drug docetaxel. Tumor-targeted superantigens (TTS) utilizes the powerful T cell activating property of a superantigen such as staphylococcal enterotoxin A (SEA) in fusion with an anti-tumor Fab-fragment to target this T cell activity against tumor cells. TTS fusion proteins are efficient in a number of experimental tumor models including the B16 mouse melanoma transfected with a human tumor-associated antigen (GA733-2 or EpCam) recognized by the C215 monoclonal antibody. The distinct mechanisms of action of TTS and docetaxel provide the prerequisites for successful combination treatment. However, as a result of the anti-proliferative properties of cytostatic drugs, chemotherapy may modify TTS induced immune activation during combination treatment.Here we evaluated the anti-tumor effects of combining C215Fab-SEA with docetaxel against B16-C215 tumors growing in the lung of C57Bl/6 mice. Both compounds generated a significant reduction in the number of B16-C215 lung tumors when administered alone. Prior treatment with docetaxel at therapeutic doses did not interfere with superantigen induced T cell activation but rather appeared to enhance the response, while simultaneous treatment was suppressive. Combining TTS and docetaxel significantly improved tumor therapy, further reducing the number of lung tumors as compared to mono therapies. Importantly, the combination treatment at timely settings synergistically prolonged long term survival in B16-C215 tumor bearing mice. The results of this study demonstrate that TTS immunotherapy is highly compatible with docetaxel and suggest a significant potential of the combination for human cancer therapy.     

Preparation and characterization of zinc oxide nanoparticles

In the present study, the zinc oxide nanoparticles (ZnO NPs) were prepared by using a sol-gel method. The characterizationof ZnO NPs, such as particle size, morphology, crystal form, optical properties and pH-responsive behavior, was carried out. The in vitro anti-tumor activity of ZnO NPs was evaluated on PC-3M and 4T1 cell lines. The results indicated that ZnO NPs were spherical NPs with uniform particle size, excellent fluorescence properties, and pH-responsive behavior. The in vitro anti-tumor activity of ZnO NPs was observed on PC-3M and 4T1 cell lines. Considering to above characteristics, ZnO NPs could be used as drug delivery carries for loading active compound performing therapeutic and diagnostic effect.     

Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is a promising treatment for breast cancer. However, its therapeutic efficiency is often compromised due to the heat-induced up-regulation of heat shock proteins, which confer photothermal resistance. To solve this urgent problem, PEGylated two-dimensional boron nanosheets (B-PEG)—which allow both multimodal imaging and photothermal conversion—were loaded with gambogic acid (GA), which can inhibit heat shock protein 90 (Hsp90). Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment. It could be used to administer mild PTT as well as chemotherapy for breast cancer, provide improved anti-tumor effects, and reduce the toxicity of PTT, all while inhibiting breast cancer growth. This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.     

Magnetic poly epsilon-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

We prepared magnetic (Fe(3)O(4)) poly epsilon-caprolactone (PCL) nanoparticles (mean diameter 164 +/- 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.     

Magnetic poly ε-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

We prepared magnetic (Fe₃O₄) poly ε-caprolactone (PCL) nanoparticles (mean diameter 164 ± 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.