bevacizumab治疗乳腺癌的基础和临床研究

分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。     

Activity of Angiogenesis Inhibitors in Metastatic Epithelioid Hemangioendothelioma: A Case Report

This report describes a patient with metastatic epithelioid hemangioendothelioma treated with bevacizumab and nanoparticle albumin-bound paclitaxel.The treatment was well tolerated and led to the stabilization of an aggressive variant of the disease. This case report is the first one that describes the activity of the combination of chemotherapy and bevacizumab in epithelioid hemangioendothelioma.Literature describing the activity of bevacizumab and other agents(thalidomide,lenalidomide,and interferon) believed to possess anti-angiogenic activities is also reviewed.     

抗血管生成剂bevacizumab治疗结直肠癌

抗血管生成剂bevacizumab能靶向结合血管内皮生长因子，从而抑制肿瘤血管新生；各期临床试验结果均显示可使结直肠癌患者获益。目前认为5mg／kg，每2周1次静脉注射的给药方式安全有效。bevacizumab的不良反应主要有高血压、蛋白尿、创伤愈合延迟、出血、胃肠穿孔和动静脉血栓事件。     

抗血管生成剂bevacizumab治疗结直肠癌

抗血管生成剂bevacizumab能靶向结合血管内皮生长因子,从而抑制肿瘤血管新生;各期临床试验结果均显示可使结直肠癌患者获益。目前认为5mg/kg,每2周1次静脉注射的给药方式安全有效。bevacizumab的不良反应主要有高血压、蛋白尿、创伤愈合延迟、出血、胃肠穿孔和动静脉血栓事件。     

贝伐单抗临床研究进展

血管生成对于实体瘤的生长和转移十分重要, 多种肿瘤细胞分泌血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF),通过这种方式诱导血管生成。应用血管内皮生长因子单克隆抗体 (rhMAb-VEGF,bevacizumab,Avastin,贝伐单抗)抗肿瘤血管生成,可以抑制肿瘤生长。以血管表皮生长因子作为治疗靶点,提供了恶性肿瘤治疗又一个新策略。     

Study protocol of the Asian XELIRI ProjecT (AXEPT)：a multinational,randomized, non-inferiority,phase III trial of second-line chemotherapy for metastatic colorectal cancer,comparing the effcacy and safety of XELIRI with or without bevacizumab versus FOLFIRI with or without bevacizumab

Background:Capecitabine and irinotecan combination therapy (XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer (mCRC). Recently, in the Association of Medical Oncology of the German Cancer Society (AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan (200mg/m2 on day 1) and capecitabine (1600mg/m2 on days 1–14), repeated every 3weeks, has shown favorable tolerability and effcacy which were comparable to those of capecitabine and oxaliplatin (XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab (BIX) as second?line chemotherapy was well tolerated and had promising effcacy in Japanese patients. Methods:The Asian XELIRI ProjecT (AXEPT) is an East Asian collaborative, open?labelled, randomized, phase III clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI (5?lfuorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with mCRC. Patients with 20years of age or older, histologically conifrmed mCRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the ifrst?line regimen will be eligible. Patients will be randomized (1:1) to receive standard FOLFIRI with or with?out bevacizumab (5mg/kg on day 1), repeated every 2weeks (FOLIRI arm) or XELIRI with or without bevacizumab (7.5mg/kg on day 1), repeated every 3weeks (XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conifdence interval (CI) upper limit of the hazard ratio was pre?speciifed as less than 1.3. Conclusion:The Asian XELIRI ProjecT is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.     

小细胞肺癌的靶向治疗进展

近年来,小细胞肺癌（SCLC）靶向治疗药物的研究明显增加。靶向治疗药物包括血管生成抑制剂、酪氨酸和Src家族激酶抑制剂、重组分子、bcl-2抑制剂、sonichedgehog信号传导通路抑制剂等,其中,研究最为广泛的是血管生成抑制剂贝伐单抗（bevacizumab）、小分子酪氨酸激酶抑制剂和沙利度胺（thalidomide）。文章就一些主要的靶向药物治疗小细胞肺癌的情况作一综述。     

贝伐单抗临床研究进展

血管生成对于实体瘤的生长和转移十分重要,多种肿瘤细胞分泌血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF),通过这种方式诱导血管生成.应用血管内皮生长因子单克隆抗体(rhMAb-VEGF,bevacizumab,Avastin,贝伐单抗)抗肿瘤血管生成,可以抑制肿瘤生长[1].以血管表皮生长因子作为治疗靶点,提供了恶性肿瘤治疗又一个新策略.     

肾细胞癌分子靶向治疗的研究进展

近年来。肾细胞癌（RCC）分子生物学研究取得了很大的进展，已确认的信号通路包括血管内皮生长因子和磷脂酰肌醇3激酶（P13K）-Akt-哺乳动物雷帕霉素靶蛋白（mTOR）通路等。RCC的靶向治疗已成为研究热点，新型靶向药物sunitinib、sorafenib、temsirolimus和bevacizumab在临床前期和临床试验中的疗效令人鼓舞.     

贝伐单抗在部分实体肿瘤中临床应用的研究进展

随着临床研究的深入,抗血管内皮生长因子(vascular endothelial growth factor,VEGF)抗体的靶向治疗越来越受到重视,其中贝伐单抗(bevacizumab,BV)成为关注的焦点,并于今年2010年5月在中国成功上市。本文就BV在转移性结直肠癌(metastatic colorectal cancer,mCRC)、非小细胞肺癌(non-small cell lung cancer,NSCLC)、转移性乳腺癌(metastatic breast cancer,mBC)及转移性肾细胞癌(metastatic renal cell carcinoma,mRCC)的靶向治疗中的研究进展作一综述。     

Quality of referral: What information should be included in a request for diagnostic imaging when a patient is referred to a clinical radiologist?

Referral to a clinical radiologist is the prime means of communication between the referrer and the radiologist. Current Australian and New Zealand government regulations do not prescribe what clinical information should be included in a referral. This work presents a qualitative compilation of clinical radiologist opinion, relevant professional recommendations, governmental regulatory positions and prior work on diagnostic error to synthesise recommendations on what clinical information should be included in a referral. Recommended requirements on what clinical information should be included in a referral to a clinical radiologist are as follows: an unambiguous referral; identity of the patient; identity of the referrer; and sufficient clinical detail to justify performance of the diagnostic imaging examination and to confirm appropriate choice of the examination and modality. Recommended guideline on the content of clinical detail clarifies when the information provided in a referral meets these requirements. High‐quality information provided in a referral allows the clinical radiologist to ensure that exposure of patients to medical radiation is justified. It also minimises the incidence of perceptual and interpretational diagnostic error. Recommended requirements and guideline on the clinical detail to be provided in a referral to a clinical radiologist have been formulated for professional debate and adoption.     

基于单病种数据库的临床科研系统的设计与研发

基于单病种数据库的临床科研系统针对特定病种的疾病,收集和整理临床数据,对疾病的发病、治疗、转归等进行记录,使得医院系统中临床数据资源价值得到极大提升,促进肿瘤临床科研水平的提高.文章分析了数据中心的现状,介绍了基于肿瘤通用标准数据集的单病种数据模型的架构,详细阐述了临床科研系统的功能,主要包括病例多维度综合查询、临床科研表单录入、随访数据共享等,讨论了系统在实际运用中存在的不足,并对科研系统的数据应用前景进行展望.     

循证医学证据对乳腺癌临床实践的影响

循证医学是遵循证据的医学,提倡将医生的个人临床实践和经验与从外部得到的最好的临床证据以及患者的意愿和要求结合起来,为患者的诊治做出最佳决策。循证医学越来越深刻地影响乳腺癌诊治的临床实践。来自于大型随机对照研究的循证医学证据可以改变临床实践,并为其提供更多选择。但是,也可能仅仅是证据,并不改变临床实践。     

Clinical trials: are they a good buy?

PURPOSE: Concern that clinical trials may be too costly has been used to justify traditionally restrictive insurer policies regarding clinical trials. Additionally, fear of insurer reimbursement denial can be a significant barrier to clinical trial participation. In this study, we reviewed the empirical data on costs of clinical trials versus standard care and summarized the current status of policy initiatives related to clinical trial insurance reimbursement. METHODS: Electronic and print data sources were searched for studies on the costs of oncology clinical trials. Information on policy initiatives for clinical trial reimbursement was obtained from the American Society of Clinical Oncology, the American Society of Hematology, and the Coalition of National Cancer Cooperative Groups and from searches of World Wide Web sites. RESULTS: Five pilot studies provided information for 377 patients on phase II/III clinical trials matched with controls on standard care. Cost estimates ranged from 10% lower to 23% higher costs/charges for clinical trials in comparison to standard medical care. Medicare, 14 states, and several private insurers now cover the costs of patient care in "qualifying" clinical trials. CONCLUSION: Findings from small pilot studies suggest that phase II and III clinical trials result in at most modest increases in cost over standard treatment costs. Also, an increasing number of policy makers have decided to support clinical trial reimbursement initiatives. It is hoped that economic data from large observational studies will facilitate widespread and permanent decisions that support reimbursement for phase I, II, and III clinical trial participation.     

Consideration of clinical development for new anticancer drugs on Japan, proposal from approval reviewer

There become problems about a delay on clinical development of anticancer drug in Japan and drug lag. I consider causes and solutions of the problems from a position of drug approval reviewer. I think the drug lag may cause by stating later state in global clinical development or stagnation of clinical trial activities. To prevail against drug lag,it is necessary to attend to multinational clinical studies,and to mature Japanese clinical trial environment and post-market planning. Then, I believe that the most important point is to make a start on early stage of global clinical development.     

The Role of Ultrasound in the Diagnosis of Parenchymal Disease in Transplanted Kidneys

The accuracy of ultrasonic diagnosis of parenchymal disease in renal transpiants was deter mined by comparing the ultrasonic diagnosis with the clinical diagnosis in 120 studies on 50 patients. The clinical diagnosis was based on clinical, biochemical and radionuclide studies, and in some cases, biopsy. At the time of the original ultrasound report clinical information was available (biopsy reports were not). All ultrasound studies were subsequently reported in random order without any clinical information and without comparison with previous or subsequent scans. This study suggests that ultrasound with or without clinical information cannot be used as a reliable basis for the diagnosis of parenchymal disease of transplanted kidneys.     

The use of halogenated thymidine analogs as clinical radiosensitizers: rationale, current status, and future prospects: non-hypoxic cell sensitizers

The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. Early clinical studies in Japan using selective intra-arterial infusions of BUdR and conventional fractionated radiation suggested improved survival in patients with primary brain tumors, although there were significant catheter-related complications. Based on recent in vivo and clinical pharmacology studies on continuous intravenous infusions of these drugs, clinical trials are underway evaluating the potential of radiosensitization in high grade gliomas and other poorly radioresponsive tumors using the technically safer intravenous route of administration. In this paper, we review the basic strategy for the use of these analogs, the ongoing clinical trials and the potential areas for future experimental and clinical studies.     

Idiotype vaccines for lymphoma: Potential factors predicting the induction of immune responses

Over the last two decades, lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand, as well as clinical benefit on the other. More recently, however, three large-scale, independent, randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial's study design than on each vaccination strategy per se. Independently of these considerations, a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that, even to date, no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced, idiotype-specific immune as well as clinical responses. The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines.     

抗肿瘤药物临床试验的研究进展

抗肿瘤药物的传统临床试验需要场地,数字临床试验不需要场地或需要场地较少,患者招募、资料收集和结果分析均在线完成.虚拟临床试验通过人工智能分析虚拟患者对数字药物的治疗反应,场地需求小且费用减少.未来的精准临床试验将让更多的受试人群入组试验并接受更优的治疗选择.抗肿瘤药物的临床试验将进入数字、虚拟和精准医学时代.     

Economic Analysis in Phase III Clinical Cancer Trials

Randomized phase III clinical trials provide important information on the efficacy of new pharmaceutical agents for cancer patients. Policy makers are showing increased interest in both economic and clinical data on new agents in order to approve pharmaceuticals for widespread use, and clinical trials have been viewed as the proper setting to evaluate these outcomes for new agents. With the recent approval of new pharmaceutical agents that have high costs, early assessments of economic benefit have taken on larger importance to physicians and patients. The integration of economic and clinical analysis in phase III clinical trials raises methodological and practical issues related to study design, collection of data on resource utilization, and generalizability of data to other settings. In this paper, we review these issues and discuss their relationship to clinical trials for new pharmaceutical products.