帕唑帕尼治疗晚期肾细胞癌的临床研究进展

靶向治疗是目前治疗晚期肾癌的新手段,多靶点的蛋白酪氨酸激酶抑制剂药物的研究也是近年来抗肿瘤药物研究的热点,盐酸帕唑帕尼为一种新型多靶点酪氨酸激酶抑制剂,临床用于治疗晚期肾癌。该药在临床前和临床研究中表现出了较强的抗肿瘤活性且耐受性较好。本文通过文献检索对该药在治疗肾癌的临床研究进展等方面进行了综述。     

晚期肾癌病人靶向药物治疗的药学监护

晚期肾癌靶向药物的作用机制及临床应用已成为治疗晚期肾癌的主要方法,但其带来包括皮肤黏膜毒性反应、高血压、疲劳、消化道反应、甲状腺功能障碍、血液学毒性和血糖、血脂代谢异常等不良反应。从治疗晚期肾癌靶向药物的药品不良反应的发现和处理及药物相互作用为切入点进行药学监护,通过严密的检测和预估来管控不良反应,作个体化给药,使患者的用药依从性增加,对提高靶向治疗效果和改善患者的生存质量尤为重要。     

索拉非尼治疗晚期肾癌的现状

随着临床对肾癌发病机制研究的不断深入,其细胞学、分子生物学领域的不断进展,其细胞信号转导路中的一些关键分子已经成为治疗的靶点,不断有新的分子靶向治疗药物问世,索拉非尼是2005年被美国FDA批准用于晚期肾癌治疗的靶向药物,美国国家综合癌症网络制定的2008年版《肾癌诊治指南》中推荐索拉非尼作为部分患者的一线治疗或者所有患者的二线治疗用药。现就索拉非尼在肾癌晚期的治疗现状、机制及应用前景作一简介。     

2011年版中国《肾细胞癌诊治指南》药物治疗原则解读

肾癌组织病理学分类复杂多样,但从临床药物治疗上分为透明细胞癌和非透明细胞癌两大类型。在我国目前对于转移性肾癌患者,药物治疗推荐分子靶向药物——索拉非尼为一线方案,其他分子靶向药物的推荐有待于中国的临床试验结果;细胞因子IFN-α或IL-2治疗对透明细胞癌类型肾癌也为一线推荐方案,而化疗可作为转移性非透明细胞类型肾癌的选择方案。伴有肾癌骨转移患者,推荐应用双膦酸盐药物,以减少骨相关事件的发生。局限性及局部浸润性肾癌患者术后尚无标准的可推荐的辅助治疗方案。     

肾癌靶向治疗现状

分子靶向治疗对肾透明细胞癌的疗效优于传统的免疫治疗,而对其他类型的肾癌亦有一定的疗效,为晚期肾癌患者带来了新的希望。本文对已经批准上市以及正在进行研究的肾癌靶向治疗药物作一综述。     

肾癌靶向治疗及联合用药的研究进展

分子靶向治疗能特异性地作用于病变部位,凭借其高效低毒的优势,成为肾癌治疗方案的新宠,然而因肾癌存在多种耐药基因,易对单一靶向药物产生耐药,大大降低其疗效,因此研究者们试图将不同靶点的药物联合应用,以期进一步提高治疗效果。文中归纳总结了肾癌的发病机制、靶向治疗的主要靶点以及联合用药的研究进展,以期为肾癌的临床用药提供参考。     

肾细胞癌新辅助靶向治疗的不良反应及其防治

肾细胞癌靶向药物主要有索拉菲尼、舒尼替尼、帕唑帕尼、贝伐珠单抗(联合IFN-α)、替西罗莫司、依维莫司及最近批准的阿西替尼,肾癌术前新辅助治疗和术后辅助治疗极大改善了进展期或转移性肾癌患者的预后。与此同时,靶向治疗药物也会引起手足皮肤反应、高血压、乏力、消化道反应等药物相关性不良反应。因此临床中及时发现并采取有效干预措施,对改善患者生活质量和提高靶向治疗效果尤为重要。     

肾癌靶向治疗药物的研究进展

肾细胞癌的发病率占恶性肿瘤的2%,传统的治疗方法是使用细胞因子(干扰素或者白介素-2),但这些免疫治疗生存优势小,疗效有限,需要开发更有效的药物。肾癌分子生物学的研究,揭示血管内皮生长因子和相关受体以及RAS/RAF/MEK/ERK和PI3K/Akt/mTOR信号传导通路与肾癌的发病密切相关,这些受体和通路促进了肿瘤细胞的生长和增殖。最近开发的药物,包括酪氨酸激酶抑制剂、单克隆抗体和mTOR抑制剂,能靶向作用于肾癌的酪氨酸激酶和细胞内通路,产生抗肿瘤作用。文中总结了肾癌发病的分子生物学机制,靶向治疗药物的作用机制以及临床评价的研究进展。     

CXCL12/CXCR4在肾癌中的研究进展

肾癌是泌尿系统常见的恶性肿瘤之一,早期症状不明显,发现时往往已发生了转移。近年来发现趋化因子CXCL12及其受体CXCR4在肾癌转移中发挥着重要的作用,对CXCR4检测有利于判断肾癌转移及患者的预后。CXCR4靶向治疗已在动物模型及临床前试验中取得了成功,有望成为治疗肾癌新的突破口。     

索拉非尼治疗肾癌的研究现状

2005年12月美国FDA批准索拉非尼用于晚期肾癌的治疗,2006年9月SFDA也批准索拉非尼在我国上市,从此开创了肾癌靶向治疗新时代。在美国国立综合癌症网络(National Comprehensive Cancer Network,NCCN)制定的2012年版《肾癌诊治指南》中,仍推荐索拉非尼作为晚期肾癌患者的一线治疗备选药物之一,中华医学会泌尿外科学会(CUA)制定的《肾细胞癌诊治指南》中推荐索拉非尼作为转移性肾癌的一线和二线治疗药物。索拉非尼上市6年来,临床上进行了一系列深入研究。     

MTT法检测肾脏肿瘤药物敏感性的分析

目的：分析肾脏肿瘤化疗药物的体外敏感性。方法：对19例肾脏肿瘤手术切除标本进行常规MTT药敏试验，检测临床常用的16种化疗药物的体外抑制率，并对检测结果进行分析。结果：肾脏肿瘤对化疗药物的敏感性不高，而且不同个体对同一药物及不同药物对同一个体的敏感性差异较大。结论：单一药物的化疗不是肾脏肿瘤治疗的理想方案。     

Emerging drugs for renal cell carcinoma

Importance of the field: The treatment of metastatic renal cell carcinoma (RCC) has evolved significantly over the past 5 years and targeted therapy has become the standard of care. However, complete and lasting responses to these drugs are still uncommon. Currently, novel agents are being tested in clinical trials.

Areas covered in this review: We discuss approved targeted agents in RCC and emphasize on emerging therapies. We searched the US National Library of Medicine (PubMed) using the terms ‘renal cell carcinoma’, ‘targeted therapy’ and ‘novel agents’, from 1990 to the present. We also searched for abstracts from the meetings of the American Society of Clinical Oncology and Genitourinary Cancers Symposium from 2007 to the present.

What the reader will gain: This paper provides understanding of the approved treatments for advanced RCC as well as the novel agents and their targeted biological pathways.

Take home message: Despite dynamic and recent advances in the management of metastatic RCC much about the molecular biology of this tumor has yet to be delineated. Even more so, strategies of sequential treatment, combination of targeted drugs, mechanisms of resistance, optimal dosages and scheduling remain areas of potential development interest.     

Emerging antiangiogenics for renal cancer

Introduction: Antiangiogenic therapy is considered to be the backbone of treatment strategy in metastatic renal cell carcinoma (mRCC). New, more focused, targeted drugs are emerging, while other targeted drugs oriented toward resistance or alternative mechanisms are under development.

Areas covered: Antiangiogenic agents include two types of agents: the monoclonal antibody, targeting vascular endothelial growth factor (VEGF), bevacizumab and the tyrosine kinase inhibitors (TKIs). Data regarding efficacy and safety of these agents are reported. Differences between the first generation of TKIs, sunitinib, sorafenib, and the new generation, pazopanib, axitinib and tivozanib are also detailed. Most of these agents have been approved in the treatment of kidney cancer in specific settings of the disease.

Expert opinion: The class of antiangiogenic drugs for treatment of mRCC is already relatively full. After ‘me-too' drugs, more targeted drugs against VEGFR have been developed but have to demonstrate a benefit in first-line treatment. Another option for the development is to combine a known drug with an antiangiogenic inhibition profile and at least one additional target involved in resistance to an antiangiogenic or in an alternative pathway. The cost of approach with targeted drugs, including antiangiogenics, has led to a tremendous increase in the cost of care in mRCC.     

Can Analgesic-abuse Nephropathy is a Fertile Groundfor for Rare Collecting Duct (Bellini Duct) Renal Cell Carcinoma or Merely a Coincidence?

Nonsteroid antiinflammatory drugs have been implicated as nephrotoxic drugs, causing both acute and chronic adverse effects that range from reversible ischemia to chronic kidney disease and urothelial tumors to renal cell carcinoma specially papillary subtype. We report one case of collecting duct (Bellini duct) renal cell carcinoma in patient with analgesic-abuse nephropathy. This young individual was suffering from ankylosing spondylitis since the age of 16 years and was consuming diclofenac and paracetamol (acetaminophen) combination for >15 years. He developed hypertension, secondary glomerulopathy, chronic kidney disease and collecting duct renal cell carcinoma.     

Sorafenib for the treatment of renal cancer

INTRODUCTION: Sorafenib was the first oral antiangiogenic multikinase inhibitor (Raf kinases, VEGF receptors 1 - 3, PDGF-beta, Flt-3, c-kit) for advanced renal cell carcinoma (RCC) to be approved. Since 2005, a total of six drugs have been approved for the treatment of RCC. AREAS COVERED: The preclinical and clinical development of sorafenib that led to its approval for advanced RCC is reviewed in this paper. Its safety, tolerability and efficacy are summarized and compared with other approved treatment options for RCC. Preliminary data on sequential treatment strategies and combination trials with other targeted drugs are also discussed. EXPERT OPINION: The efficacy and good tolerability of sorafenib in patients with RCC has already been confirmed by numerous studies. The drug proved to be suitable for patients of any age, with respect to efficacy and safety. Sequential use of sorafenib and other targeted drugs is characterized by only limited cross-resistance and many studies seem to indicate more clinical benefits and longer overall progression-free survival when sorafenib is administered as a first-line therapy. However, the optimal sequential therapy remains to be determined within prospective trials, such as the SWITCH study. In addition, we need predictive biomarkers to preselect the patients with the best chances of benefiting from sorafenib, in the context of personalized medicine.     

VEGF inhibitors in metastatic renal cell carcinoma: current therapies and future perspective

Metastatic renal cell carcinoma (RCC) is predominantly refractory to treatment with traditional cytotoxic chemotherapies, and until recently management options were limited to immunotherapy, palliative care, or phase I trials. The past five years have witnessed a major change in the treatment of advanced RCC with the introduction of targeted therapies that derive their efficacy through affecting angiogenesis. The main class of agents involves drugs that target the vascular endothelial growth factor (VEGF). Several VEGF inhibitors are now approved for the treatment of metastatic RCC. The field is expanding rapidly with goals including 1) developing novel more potent and better tolerated agents and 2) defining the role of combination and sequential anti-VEGF regimens.     

Programmed Cell Death Pathways and Current Antitumor Targets

Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.     

靶向药物联合化疗治疗晚期非小细胞肺癌的临床分析

目的 分析研究靶向药物联合化疗治疗晚期非小细胞肺癌（NSCLC）的疗效.方法 选取2011-2012年我院收治的晚期NSCLC患者46例,将其随机划分为两组.甲组采用常规的化疗药物治疗,乙组在给予常规化疗基础上使用靶向药物治疗,比较两组治疗效果.结果 甲组临床疗效优于乙组,差异有统计学意义（P＜0.05）;两组患者血红蛋白、血小板、白细胞下降及皮疹、消化道反应发生率比较差异无统计学意义（P＞0.05）.结论 给予晚期NSCLC患者采用靶向药物联合化疗治疗,可显著提高临床治疗效果.