铂类抗肿瘤药物的发展历程及临床评价

近年来,铂类抗肿瘤药物的临床研究进展迅速,其抗肿瘤谱广,抗肿瘤活性增强,不良反应降低,已成为目前有关抗肿瘤药物研发的重要领域。新的铂类抗肿瘤药物将从那些在临床研究中显示出低毒性、抗肿瘤谱广、与现有药物无交叉耐药性的化合物中产生。该文对铂类抗肿瘤药物的抗肿瘤机理、研究进展和未来研究趋势进行了综述;     

回顾铂类化合物的发展历程及临床评价

目的:简述铂类化合物抗肿瘤药的进展和临床应用评价.方法:通过国内、外近期文献进行综述.结果和结论:近30年来,铂类化合物的临床研究进展迅速,其抗肿瘤谱广,抗癌活性增强,不良反应降低.已成为目前有关抗肿瘤药物研发的重要领域,铂类化合物将在抗肿瘤中发挥更大作用.     

铂类抗肿瘤药物及其临床研究进展

铂类药物是一类细胞周期非特异性抗肿瘤药物，抗瘤谱广，DNA是其作用靶点。药物进入体内后，以水合阳离子形式与DNA等生物大分子结合形成共价键。使DNA链局部扭结或解旋，致使DNA复制、转录失败，从而造成肿瘤细胞死亡。以铂为中心的结构变化衍生出了多种新型铂类药物。该文介绍了铂类药物及其临床研究的进展。     

铂类抗肿瘤药物的研究进展

目的综述铂类抗肿瘤药物的作用机制及新型铂类抗肿瘤药物的设计策略。方法查阅国内外近10年相关文献,对其进行归纳、总结,从铂类抗肿瘤药物的研究概况、作用机制及新型药物的设计策略几方面进行了介绍。结果铂类药物在抗肿瘤领域发挥着重要作用,为解决现有药物存在的耐药性、组织毒性等缺点,靶向给药、Pt(Ⅳ)模式前药、单功能团铂类抗肿瘤药物等更先进的设计策略越来越受到重视。结论铂类药物及新型铂类药物仍是抗肿瘤药物的研究热点,值得进一步研究开发。     

铂类抗肿瘤药的进展与临床评价

目的:探讨铂类抗肿瘤药的临床特点及其研究进展,为临床应用提供参考。方法:通过查阅国内外相关文献,系统地了解铂类抗肿瘤药的临床作用及相关不良反应;并检索近年上市、未获批准及正在进行临床研究的铂类药物,以分析其临床发展趋势。结果与结论:在过去的10年间,药物研发转向注重药物运输靶向介质,这些新药在保留传统铂类化合物的活性的同时,在很大程度上减少了传统铂类药物的不良反应。     

铂类抗肿瘤药物的应用现状及合理性探析

目的 研究铂类抗肿瘤药物实际应用现状与应用合理性分布情况。方法 在本院药学部抗肿瘤药物应用记录表中选出13 400份铂类抗肿瘤药物处方,选定时间为2021年1月至2022年1月,比较铂类抗肿瘤药物的处方使用量、销售金额、用药期间不良反应发生率与不合理用药行为占比率。结果 13 400份铂类抗肿瘤药物处方中奥沙利铂处方占比率60.07%,奈达铂20.90%,顺铂11.19%,卡铂7.88%;销售金额奥沙利铂最高,卡铂药物每日规定剂量最多为200 mg/m²;其中150例奈达铂药物使用者不良反应率33.33%,奥沙利铂3.33%,不良反应率数据有统计学意义(P <0.05)。4种常用铂类药物不合理用药率均低于1%。结论 铂类抗肿瘤药物实际应用中奥沙利铂、奈达铂、顺铂与卡铂药物的使用量较大,奥沙利铂销售总金额最高,奈达铂易出现不良反应,需在药物应用环节严控用药合理性,加强不良反应监督,充分展现药效。     

奈达铂联合紫杉醇治疗晚期非小细胞肺癌的临床观察

铂类化合物是临床上治疗实体瘤的常用药物,奈达铂作为一种第二代铂类抗癌药,具有抗肿瘤谱广,不良反应轻,与其他铂类药物无完全交叉耐药等特点,本文结合临床实践,对其近期疗效和不良反应进行对比分析,现报道如下。     

几种铂类抗肿瘤药物的临床应用进展

恶性肿瘤是世界公认的对人类健康危害最严重的疾病之一 ,其危害性仅次于心血管疾病。因此 ,加强肿瘤治疗的研究 ,提高现有各种治疗手段的效果 ,降低癌症死亡率 ,减少复发率 ,改善癌症患者的生活质量 ,是临床医务工作者的急迫职责。在肿瘤治疗中 ,化疗是当前肿瘤治疗的重要方法之一。在众多化疗药物中 ,铂类配合物是一类抗肿瘤作用较强、抗肿瘤谱较广的药物。现介绍临床使用以及正在研究中的铂类金属抗肿瘤药物。1　临床使用的铂类抗肿瘤药物从Rosenberg偶然发现铂配合物能抑制细胞分裂后 ,即开创了铂类抗肿瘤药物的研究。随着上世纪 70年代…     

第三代铂类抗肿瘤药物洛铂(Lobaplatin)

铂配合物的生物活性发现于1965年,第一代铂类药物顺铂、顺氯氨铂、锡铂,第二代铂类药物卡铂、奈达铂、依铂、碳铂、卡波铂,第三代铂类药物奥沙利铂、洛铂、赛特铂、诺贝铂等陆续问世,目前,还有多个铂类抗肿瘤药物进入临床研究阶段,如环铂、欧玛铂、SK12053、L—DDP、TRK-710、BBR3464。因现在临床使用的抗肿瘤药均为静脉给药,     

吉西他滨联合铂类治疗卵巢癌的研究进展

吉西他滨(gemcitabine,GEM)是嘧啶类抗肿瘤药物,已广泛用于实体瘤的治疗,在卵巢癌治疗中,吉西他滨单药或铂类联合方案,是晚期复发转移卵巢癌的标准方案之一.另有临床研究显示,吉西他滨与铂类联用可作为卵巢癌的一线治疗方案.本文简要介绍了吉西他滨联合铂类治疗卵巢癌的相关信息.     

铂类抗肿瘤配合物的研究进展

铂类药物因抗癌谱广、疗效显著而在临床中被广泛使用。自1978年顺铂应用于临床以来,卡铂、奥沙利铂相继被美国FDA批准,乐铂、奈达铂和依铂分别在中国、日本以及韩国上市。然而,铂类药物的毒副作用和耐药性大大限制了其应用和开发。为提高铂类药物的疗效以及克服其缺陷,大量的新型铂类配合物被设计合成,并在不同阶段开展疗效试验。除与顺铂类似的铂(Ⅱ)配合物之外,近年来作为前药的铂(Ⅳ)配合物也被广泛研究。从铂(Ⅱ)配合物和铂(Ⅳ)配合物2个方面,总结近年来铂类抗肿瘤配合物取得的研究进展,并对配体的选择与配合物设计、作用机制、抗肿瘤效果以及临床应用前景进行概述,以期对今后的新药开发和临床应用有所裨益。     

Nanocarriers for delivery of platinum anticancer drugs

Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs.     

铂类抗肿瘤药物的研究现状

自从顺铂作为第一代抗肿瘤药物被开发利用以来，人们一直在寻找广谱、高活性、低毒性和无交叉耐药性的铂类抗肿瘤药物，合成和筛选出各种铂络合物。分别介绍根据不同设计思路合成的四价铂络合物、具有活性配体的铂络合物、生物载体为配体的靶向铂络合物、反式铂络合物和具有立体位阻效应的铂络合物及其抗肿瘤活性，综述当前铂类抗肿瘤药物的研究现状。     

抗肿瘤药培美曲塞的临床应用研究近况

抗肿瘤药培美曲塞能抑制叶酸代谢所依赖的几个关键酶的活性,从而多靶点、多方位地抑制肿瘤细胞的生长。临床前研究与临床试验都表明,培美曲塞能抗多种肿瘤,且与许多其它抗癌药有协同增效作用。虽然目前该药仅被批准用于恶性胸膜间皮瘤和非小细胞肺癌,但其在临床上还有更大的潜力。介绍近年来培美曲塞的临床应用研究情况,包括与铂络合物、吉西他滨、长春瑞滨、紫杉醇和伊立替康等药物联用的临床疗效以及单独或与其它抗癌药联用于治疗头颈部癌、乳腺癌、胃癌、肠癌及膀胱癌等的初步临床研究结果。     

Drug discovery research on in vivo antitumor-active azolato-bridged dinuclear Pt(II) complexes

Cis-diamminedichloridoplatinum(II) (cisplatin), which was first introduced as a clinical anticancer agent in the 1970s, is still among the most-utilized agents in current cancer chemotherapy. The discovery of cisplatin antitumor activity has catalyzed drug discovery research on antitumor platinum coordination compounds with improved efficacy. Some of new compounds show fewer side effects or expanded clinical applications. Apart from some clinical inconveniences, such as side effects, the high therapeutic efficacy of platinum-based agents implies that further modifications may lead to more effective anticancer platinum drugs which are effective against cancers that are typically resistant to chemotherapy, such as pancreatic cancer, and platinum-refractory cancer. Most of the cisplatin analogs cause cross-resistance to cisplatin, probably because of the similar biological consequences. It is suggested that platinum complexes which interact with DNA; the most probable target molecule, through a mechanism different from that of cisplatin can provide unique anticancer spectra required for next-generation anticancer drugs. Therefore, we synthesized a series of azolato-bridged dinuclear Pt(II) complexes with a general formula, [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-azolato)](2+), which can form 1,2-intrastrand crosslinks with a minimal DNA distortion, whereas clinical platinum-based drugs provide 1,2-intrastrand crosslink with severe DNA distortion. Indeed, they exhibit much higher in vitro cytotoxicity than cisplatin, and we have recently found one of the dinuclear Pt(II) complexes exhibits markedly high in vivo antitumor efficacy against pancreatic cancer. Here, I update our drug-discovery research on the series of azolato-bridged dinuclear Pt(II) complexes that may be more effective and safer than current anticancer chemotherapeutic agents.     

铂类抗肿瘤药物耐药机制的研究进展和应对策略

铂类抗肿瘤药物是目前临床应用最广泛的一线化疗药物,疗效显著。但临床使用过程中出现的非小细胞肺癌、乳腺癌、卵巢癌等铂类药物耐药问题,严重影响了铂类药物的疗效,也极大限制了铂类药物的使用。铂类药物耐药是由多种因素引起的,目前关于铂类药物的耐药机制主要有以下几个方面：减少细胞内铂的积累、促进细胞内铂的失活、DNA的损伤修复能力增强、肿瘤细胞凋亡抑制作用增强等。本文就铂类抗肿瘤药物的耐药机制和应对策略做一综述,为铂类抗肿瘤药物的研发提供思路,为克服临床铂类药物耐药问题提供参考。     

Recent developments in the field of anticancer platinum complexes

Cisplatin, carboplatin and oxaliplatin continue to be among the most efficient anticancer drugs in world-wide clinical use so far. In particular, cisplatin has shown a remarkable therapeutic efficacy in a broad spectrum of solid tumors and outstanding activity against metastatic testicular germ-cell cancer with cure rates of about 90% of cases. Nevertheless, the dose-limiting severe toxic side-effects of platinum-based chemotherapy, the problem of inherent or therapy-induced resistance, the limited activity in a range of tumors, and the meager tumor selectivity are the motivation for tremendous efforts and inventions in the development of novel anticancer platinum drugs. This article reviews the most recent patents in this field of research, covering the following strategies in the design of promising anticancer platinum complexes: (i) synthesis of new anticancer platinum complexes, using combinatorial chemistry and high throughput synthesis and screening, (ii) activation of platinum complexes in the tumor tissue, (iii) accumulation of platinum complexes at the tumor site, (iv) novel platinum complexes, displaying activity against cisplatin resistant cells and as inhibitors of specific biological functions, and (v) direct derivatives of classical anticancer platinum drugs in clinical use.     

Recent developments in the field of tumor-inhibiting metal complexes

25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.