Photodynamic therapy in oncology

Photodynamic therapy (PDT) is a cancer treatment modality that is based on the administration of a photosensitiser, which is retained in tumour tissues more than in normal tissues, followed by illumination of the tumour with visible light in a wavelength range matching the absorption spectrum of the photosensitiser. The photosensitiser absorbs light energy and induces the production of reactive oxygen species in the tumour environment, generating a cascade of events that kills the tumour cells. The first generation photosensitiser, Photofrin^® (porfirmer sodium), has been approved for oesophageal and lung cancer in the US and has been under investigation for other malignant and non-malignant diseases. Sub-optimal light penetration at the treatment absorption peak of Photofrin and prolonged skin photosensitivity in patients are limiting factors for this preparation. Several new photosensitisers have improved properties, especially absorption of longer wavelength light which penetrates deeper into tissue and faster clearance from normal tissue. This paper reviews the current use of first- and second-generation photosensitisers in oncology. The use of PDT in oncology has been restricted to certain cancer indications and has not yet become an integral part of cancer treatment in general. The main advantage of PDT is that the treatment can be repeated multiple times safely, without producing immunosuppressive and myelosuppressive effects and can be administered even after surgery, chemotherapy or radiotherapy. The current work on new photosensitisers and light delivery equipment will address some of the present shortcomings of PDT. Much has been learned in recent years about the mechanisms of cellular and tissue responses to PDT and protocols designed to capitalise on this knowledge showed lead to additional improvements.     

我院小儿肿瘤科住院患儿超说明书用药分析

目的：调查我院小儿肿瘤科住院患儿超说明书用药情况,为临床合理用药提供参考。方法：采用回顾性研究方法,随机抽取我院小儿肿瘤科2014年9月至2015年8月的住院患儿300例,依据药品说明书和相关文献,分析超说明书用药情况。结果：300例患儿共计医嘱625 9条,涉及药品228种。300例患儿中,超说明书用药的患儿188例（62.67％）,超说明书用药医嘱1 007条（16.09％）,超说明书用药涉及药品49种。结论：我院小儿肿瘤科普遍存在超说明书用药情况,给医疗纠纷事件的发生埋下了隐患,呼吁有关部门采取有效措施进行监管,关注儿童用药,杜绝不必要的超说明书用药。     

心理护理应用于肿瘤外科护理的效果分析

目的分析对肿瘤外科患者采用心理护理干预效果。方法 156例择期手术患者随机分为试验组和对照组各78例。对照组:采用常规护理;试验组:在对照组常规护理基础上实施心理护理干预。结果试验组在尿管导致不适、切口疼痛、担心疾病预后、引流管牵制等评分上明显优于对照组(P<0.05)。然而两组患者在睡眠障碍评分上进行比较,差异不具有统计学意义(P>0.05)。结论对肿瘤外科患者实施心理护理干预,能够有效地降低患者焦虑和紧张等不良情绪。     

Phase I trials in paediatric oncology — the European perspective

The current recommendations for Phase I trials should allow more confident interpretation of the toxicity and efficacy of new agents by providing a framework for multicentre and international co-operation. An overview of the aims and designs of Phase I trials is presented, along with a summary of current and recently published United Kingdom Childrens Cancer Study Group Phase I trials, and a discussion of some of the difficulties faced in the methodology and evaluation of Phase I studies in children. Address for offprints: E.J. Estlin, Dept. of Child Health, Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom     

住院老年恶性肿瘤患者的死亡分析研究

目的对我院近4年收治的住院老年恶性肿瘤死亡患者的病案资料进行回顾性调查和统计分析,探讨老年恶性肿瘤死亡分布的特征、死亡原因等,以提供临床医生制定相应的防治措施依据。方法从2009年1月～2012年12月收住我院的病案数据库中收集〉60岁老年恶性肿瘤死亡患者的资料,根据ICD-10进行死因分类并流行病学分析,计算年病死率、分析研究其年龄分布、性别与病种的分布、合并症情况、死亡月份的分布、死亡原因。结果随着年龄的增加,病死率逐渐增加,在70～80岁年龄组达到高峰;60～70岁年龄组随着时间的推移,逐年死亡发生率下降,而70岁以上年龄组则发生率逐年增加;前五位的病种依次为：肺癌、肝癌、大肠癌、胃癌、头颈部癌。在男性,前五位的病种依次为：肺癌、胃癌、大肠癌、肝癌、头颈部癌;在女性,前五位的病种依次为：肝癌、大肠癌、胃癌、头颈部癌、胰胆管癌。大多病种死亡人数男性多于女性;合并症大多为老年性痴呆、脑萎缩、心血管病、糖尿病、前列腺增生、肺部感染;死亡月份的分布显波浪状曲线,2月份达到第一个高峰,8月份达到第二个高峰;主要死于全身多器官衰竭、呼吸衰竭、消化道出血、肝性脑病、肠梗阻。结论对老年恶性肿瘤住院患者的病情及各种影响因素应进行充分的评估,采用有效的综合防治措施,以使患者得到改善症状,提高生存质量,延长生存期。     

美国肿瘤专科药师的培养和资格认证

目的：介绍美国肿瘤专科药师的培养和资格认证要求与考核内容,以及肿瘤专科药师的工作内容,以备借鉴。方法：检索、阅读、总结相关内容及文献,并进行介绍。结果：美国肿瘤专科药师培养和认证体系为临床肿瘤治疗团队输送了大量人才,也为药师地位的确立和新业务的拓展提供了基础。     

Targeted approaches to childhood cancer: progress in drug discovery and development

Introduction: Cancer is a leading cause of death in childhood. Encouraging progress has been made in the treatment of childhood malignancies, but there is an unmet need for new drugs to improve survival and reduce treatment-associated toxicities. Drug development in paediatric oncology has specific requirements with regard to the patient population and the regulatory background and presents several unique challenges that need addressing.

Areas covered: This review discusses the current framework of paediatric oncology drug development and some of the specific challenges in pre-clinical and clinical research. The authors discuss the recent developments in the targeting of various signalling pathways. These pathways represent a selection of targets that have been identified by pre-clinical and clinical investigators to be highly relevant in paediatric malignancies.

Expert opinion: The development of targeted agents in paediatric oncology must be driven by knowledge of tumour biology. Predictive and pharmacodynamic biomarkers should be incorporated within paediatric early clinical trials wherever possible. Faster dose-escalation, limited numbers of cohorts and novel adaptive designs can help to make paediatric early clinical trials more efficient. Close collaboration between academic/clinical researchers, the pharmaceutical industry, regulatory bodies and parent groups are crucial in overcoming the challenges associated with paediatric oncology drug development.     

雄激素阻断提高局限性晚期前列腺癌放疗患者总生存率和疾病特异性生存率的Meta分析

目的:探讨雄激素阻断对局限性晚期前列腺癌放疗患者总生存率和疾病特异性生存率的影响。方法:检索Pubmed、OVID、Cochrane Library、CBMdisc、CNKI数据库有关雄激素阻断治疗局限性晚期前列腺癌放疗患者的随机对照试验。利用Jadad量表和分配隐藏进行方法学质量评估,按照纳入和排除标准筛选文献。采用RevMan4.2软件进行统计分析。结果:纳入本次Meta分析的研究6篇。累计病例2896例,其中联合治疗组1581例,单独放疗组1315例。联合治疗组的总生存率(68.4%,1081/1581)较单独放疗组(57.8%,760/1315)有所提高,合并相对危险度RR值为1.14(95%CI1.07～1.20,P<0.00001)。疾病特异性生存率在联合治疗组(87.5%,1383/1581)与单独治疗组(79.4%,1044/1315)差异有统计学意义,合并RR值为1.09(95%CI1.04～1.15,P=0.0008)。结论:与单独放疗相比,雄激素阻断联合放疗能够改善局限性晚期前列腺癌患者总生存率和疾病特异性生存率。     

我国肿瘤科临床药师的发展现状

目的了解我国肿瘤科临床药师工作的开展状况,为不断拓展临床药学工作提供参考。方法检索有关肿瘤科临床药师工作文献52篇,采用文献计量学方法分析文献的发表时间、期刊、研究内容、研究方法等分布特点。结果不同年度时间段,有关文献量呈逐渐上升趋势。文献分布在26种生物医学期刊,其中《中国药房》、《中国医院药学杂志》、《医药导报》、《中国药学杂志》、《中国药师》为刊载临床药师工作相关文献的核心期刊;文献中研究方法主要以综述和实践报告为主,其中临床药师实践类文献2010年以后明显增多。结论自2000年以来,我国肿瘤科临床药师工作取得了一定进步,但肿瘤科临床药师实践工作仍处于探索阶段,有待进一步探索建立临床药师有效培养路径及其药学服务考核评价体系。     

肿瘤科临床药师参与癌痛个体化治疗的实践体会

目的 探讨临床药师如何参与癌性疼痛的治疗,更好地为临床疼痛治疗提供药学服务。方法 临床药师加入疼痛治疗团队,熟练掌握药物不良反应、禁忌证、代谢排泄途径、相互作用等特点,结合考虑患者年龄、并发症、肝肾功能、病史等具体情况,以说明书及相关文献为循证依据,与医师探讨镇痛治疗方案,为患者选用适宜药物。结果 临床药师提出建议及意见多为医师认可并接受,从而提高临床疼痛治疗的合理性,降低或避免不良反应。结论 镇痛治疗中,临床药师可通过全面考虑药物特点并结合患者具体情况,分析比较同类药物,根据患者个体特征,为患者选择最适宜药物。     

美国丹娜法伯癌症中心肿瘤临床药师在门诊化疗中的角色和启示

目的:通过介绍美国丹娜法伯癌症中心门诊化疗模式及肿瘤临床药师的作用,为我国肿瘤临床药师参与门诊化疗工作拓展思路。方法:参观访问美国丹娜法伯癌症中心并参与临床实践,了解其门诊化疗模式及临床药师在其中的工作和角色。结果:美国的门诊化疗是基于医生、药师、护士共同工作的团队模式,临床药师的主要工作内容为审核处方、向医生护士提供用药建议、向患者提供用药咨询与用药教育等,其作用是根据医保政策减少患者和医院的药品花费,利用药学知识降低医护和患者的用药风险,保障门诊化疗的用药安全。结论:美国门诊化疗模式有值得借鉴之处,我国肿瘤临床药师可以根据我国国情开展很多工作,在门诊化疗的发展中发挥较大作用。     

肿瘤专业中药注射剂的现状与思考

通过分析肿瘤专业中药注射剂生产及临床应用现状及存在的问题,探讨肿瘤专业中药注射剂研发思路和方向。目前肿瘤相关中药注射剂有20余种,其应用有越来越普遍之势。社会经济及医、患三方成为推动肿瘤相关中药注射剂制售的现实因素。与此同时肿瘤相关中药注射剂在其基础研究、生产、推广应用及不良反应监测等方面也存在诸多问题。应从科研导向、药品研发、生产销售等各个环节严格把关,才能保障肿瘤专业中药注射剂的疗效和安全性,促进中药注射剂的健康发展。     

中晚期宫颈癌放射治疗前后MRI检查的应用

目的 探讨中晚期宫颈癌放射治疗前后的MRI表现，评价MRI在宫颈癌治疗过程中的临床应用价值。方法对22例中晚期宫颈癌分别进行放射治疗前后MRI检查，对肿瘤大小、信号等进行对比。结果MRI检查成功率为100％，22例患者中．肿瘤明显缩小或消失18例，轻度缩小4例，肿瘤总体信号降低19例．信号不均匀3例，淋巴结缩小或消失6例。宫颈癌放射治疗前后与宫旁组织具有良好的自然对比，观察内容均清晰显示。结论MRI检查对宫颈癌显示清楚，分期可靠，对放射治疗疗效及预后评价具有重要意义。     

临床药师参与肿瘤内科全医嘱审核情况分析

目的 全面了解肿瘤内科医嘱情况,保证临床用药的合理安全。方法 临床药师对肿瘤内科实行全医嘱审核,并将2017年的审核情况进行总结分析。结果 2017年全年,临床药师共审核肿瘤内科医嘱16 754条,其中不合理医嘱201条,总不合理率为1.20%。第1季度、第2季度、第3季度和第4季度不合理率分别为1.62%,1.42%,0.95%和0.77%。不合理医嘱包括化疗药物预处理不适宜、给药频次不适宜、溶媒使用不适宜、给药时间不适宜、适应证不适宜、给药剂量不适宜、给药途径不适宜、重复用药及遴选药品不适宜等9种类型,占不合理医嘱总数的比例分别为17.4%,15.9%,15.4%,13.4%,11.9%,10.9%,9.0%,4.0%和2.0%。结论 2017年肿瘤内科医嘱不合理率按季度呈下降趋势,在一定程度上证实临床药师全医嘱审核和及时干预沟通对合理用药具有较好的作用。     

Positron emission tomography (PET): Expanding the horizons of oncology drug development

Positron emission tomography (PET) allows three-dimensional quantitative determination of the distribution of radioactivity permitting measurement of physiological, biochemical, and pharmacological functions at the molecular level. Until recently, no method existed to directly and noninvasively assess transport and metabolism of neoplastic agents as a function of time in various organs as well as in the tumor. Standard preclinical evaluation of potential anticancer agents entails radiolabeling the agent, usually with tritium or ¹⁴C, sacrifice experiments, and high-performance liquid chromatography (HPLC) analysis to determine the biodistribution and metabolism in animals. Radiolabeling agents with positron-emitting radionuclides allows the same information to be obtained as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling in combination with PET scanning. In phase I/II human studies, classic PK measurements can be coupled with imaging measurements to define an optimal dosing schedule and help formulate the design of phase III studies that are essential for drug licensure [1]. Many of the novel agents currently in development are cytostatic rather than cytotoxic and therefore, the traditional standard endpoints in phase I and II studies may no longer be relevant. The use of a specialized imaging modality that allows PK and pharmacodynamic (PD) evaluation of a drug of interest has been proposed to permit rapid and sensitive assessment of the biological effects of novel anticancer agents. The progress to date and the challenges of incorporating PET technology into oncology drug development from the preclinical to clinical setting are reviewed in this article.     

Serendipitous Discovery of a Prodrug of a PARP‐1 Inhibitor

During SAR development of previously reported pyrrolocarbazole 1 , a potent PARP‐1 inhibitor, compound 14 , was discovered serendipitously to be a prodrug of compound 1 .     

Student Performance in a Pharmacotherapy Oncology Module Before and After Flipping the Classroom

Objective. To determine if a flipped classroom improved student examination performance in a pharmacotherapy oncology module.Design. Third-year pharmacy students in 2012 experienced the oncology module as interactive lectures with optional case studies as supplemental homework. In 2013, students experienced the same content in a primarily flipped classroom. Students were instructed to watch vodcasts (video podcasts) before in-class case studies but were not held accountable (ie, quizzed) for preclass preparation. Examination questions were identical in both cohorts. Performance on examination questions was compared between the two cohorts using analysis of covariance (ANCOVA), with prior academic performance variables (grade point average [GPA]) as covariates.Assessment. The students who experienced the flipped classroom approach performed poorer on examination questions than the cohort who experienced interactive lecture, with previous GPA used as a covariate.Conclusion. A flipped classroom does not necessarily improve student performance. Further research is needed to determine optimal classroom flipping techniques.