非小细胞肺癌的靶向治疗进展

化学治疗晚期非小细胞肺癌疗效似已达到平台,靶向药物是进一步提高疗效的关键.尽管第一代靶向治疗药物开发的种类繁多,但仅有少数药物在前瞻性、随机的Ⅲ期临床试验中显示出生存优势.第二代靶向治疗药物--多靶点抑制剂,可同时阻断肿瘤多个的信号传导,临床试验的初步结果表明,毒副作用可以耐受,效果较好,治疗晚期非小细胞肺癌已显示出较好的应用前景.     

小细胞肺癌靶向治疗研究进展

20世纪90年代以来,肺癌靶向治疗的研究工作不断深入。目前,全球有近80种靶向治疗制剂已经或正在进行临床试验,其中与肺癌相关者近50种。以肿瘤血管生成和表皮生长因子受体(ep iderm al grow thfactor receptor,EGFR)为靶点的药物占总数的60%,首个EGFR抑制剂——吉非替尼已于2005年2月在我国批准上市。小细胞肺癌(sm all cell lungcancer,SCLC)对放疗、化疗较为敏感,近期疗效较好,但极易出现复发,生存期短,国内外大量学者对小细胞肺癌的靶向治疗进行了研究。本文就小细胞肺癌中信号转导抑制剂的靶向治疗,以血管生成为靶点的靶向治疗及以…     

非小细胞肺癌靶向治疗的进展

自本世纪初靶向治疗新药Gefitinib应用于非小细胞肺癌，短短7～8年中，非小细胞肺癌的靶向治疗经历了曲折的发展，人们对靶向治疗的态度也经历了惊叹、怀疑、肯定、客观的过程。随着对靶向药物了解的深入，以及新的靶向药物的不断涌现，晚期非小细胞肺癌的治疗策略可能面临改变。     

非小细胞肺癌的靶向性治疗

靶向性治疗是指使用药物特异性干扰参与肿瘤发生和进展的异常分子或生物学通路治疗非小细胞肺癌的靶向药物包括EGFR家族抑制剂，血管生成抑制剂，信号传导抑制剂，凋亡诱导剂，类花生酸（eicosanoid）通路抑制剂。获得批准上市的有Gefitinib和Erlotinib，但更多的在进行临床试验。     

非小细胞肺癌伴随诊断的研究进展

非小细胞肺癌是最常见且死亡率最高的肿瘤，不同的非小细胞肺癌患者的驱动基因不同，且大多数患者通常发现晚，预后差。针对不同患者制定个性化治疗方案，选择适合的靶向药物是非小细胞肺癌的最佳治疗方案。伴随诊断通过整合多种体外诊断技术，为患者提供精确的靶向用药信息，避免患者因选择不适合的靶向药物造成不良后果。本文对非小细胞肺癌伴随诊断中的靶向生物标记物、检测技术及伴随诊断的国内外现状进行概述。     

放疗联合分子靶向药物治疗非小细胞肺癌的研究进展

目的 随着对肿瘤和正常组织放射生物学机制的深入研究以及分子靶向药物对放射生物学机制影响的进一步认识,出现了许多联合放疗和分子靶向药物的临床前期和临床试验,初步验证了这种联合治疗模式的可行性和疗效。本文就放疗联合分子靶向药物治疗非小细胞肺癌的可能机制和临床试验的初步结果作一综述。     

三代EGFR-TKI一线治疗非小细胞肺癌临床试验统计学解读：AENEAS研究、FLAURA研究和FURLONG研究

摘 要：针对表皮生长因子受体（EGFR）的靶向治疗显著改善了具有EGFR敏感突变非小细胞肺癌患者的预后。EGFR-TKI已成为携带EGFR敏感突变非小细胞肺癌患者的标准一线治疗，并改变了晚期非小细胞肺癌领域的治疗格局。目前，国内外先后有多个三代EGFR-TKI药物相关研究开展，包括AENEAS研究、FLAURA研究和FURLONG研究等。基于此，笔者针对该领域临床试验进行统计学解读，通过研究终点设计、终点评估方法、关键亚组分析等角度进行剖析，以期有助于深入理解非小细胞肺癌领域临床试验设计及其对结果解读的影响，助力提升该领域中EGFR-TKI药物开发并惠及广大患者。     

检测NSCLC血清循环EGFR突变值得推广

正靶向治疗的涌现极大的改善了晚期非小细胞肺癌患者的预后。目前国内外多宗大规模的临床试验已经证明,对于有表皮生长因子受体(EGFR)基因突变的进展期非小细胞肺癌患者,接受EGFR酪氨酸激酶     

分子靶向治疗在Ⅲb/Ⅳ期非小细胞肺癌一线治疗中的应用

Ⅲb/Ⅳ期非小细胞肺癌一线化疗的疗效已进入瓶颈期.分子靶向药物的出现,给晚期非小细胞肺癌的一线治疗带来了划时代的变革,极大地改善了晚期非小细胞肺癌患者的生活质量、提高了生存期.全文就分子靶向治疗在晚期非小细胞肺癌一线治疗中的应用作一综述.     

中医药维持治疗晚期非小细胞肺癌的可行性探讨

晚期非小细胞肺癌维持治疗越来越受肯定,现以化疗或靶向治疗模式为主,但化疗药物的毒性蓄积,甚至过度治疗等问题却成为维持化疗的瓶颈,靶向药物的价格昂贵也给患者维持带来不便,中医药治疗晚期肺癌在改善临床症状、提高生活质量及延长生存期方面彰显优势.全文就中医药维持治疗晚期肺癌的可行性作一分析.     

Docetaxel in advanced non-small cell lung cancer

Based on the survival benefit demonstrated in large randomized clinical trials, docetaxel is approved for the treatment of advanced non-small cell lung cancer (NSCLC) in both the first- and second-line settings. The efficacy of docetaxel in combination with cisplatin is equivalent to some, and superior to other, platinum-based doublets for first-line management of NSCLC, and has a manageable toxicity profile. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy of patients with advanced NSCLC. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II studies. This article reviews recent studies of docetaxel as a single agent and in combination regimens with cytotoxic and more recent targeted agents in the management of advanced NSCLC.     

晚期非小细胞肺癌维持治疗的临床研究进展

 4～6个周期含铂类的一线化疗方案是晚期非小细胞肺癌目前的标准治疗,但对一线治疗后有效和稳定的患者,如何选择安全有效的药物来拓展一线治疗疗效及带来进一步的临床获益是目前值得关注的问题。文章就以化疗和分子靶向药物作维持治疗的临床进展作一介绍。     

Docetaxel in the treatment of advanced non-small-cell lung cancer

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non-small-cell lung cancer (NSCLC). Docetaxel is the only agent currently approved for both first- and second-line treatment of advanced NSCLC. Multiple randomized clinical trials have established the efficacy of platinum–docetaxel regimens for the first-line treatment of advanced NSCLC. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II trials. This review article summarizes recent studies of docetaxel as a single agent and in combination regimens with cytotoxic or targeted therapies in the management of patients with advanced NSCLC.     

Docetaxel in the treatment of advanced non-small-cell lung cancer

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non-small-cell lung cancer (NSCLC). Docetaxel is the only agent currently approved for both first- and second-line treatment of advanced NSCLC. Multiple randomized clinical trials have established the efficacy of platinum-docetaxel regimens for the first-line treatment of advanced NSCLC. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II trials. This review article summarizes recent studies of docetaxel as a single agent and in combination regimens with cytotoxic or targeted therapies in the management of patients with advanced NSCLC.     

EGFR inhibitors with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer

Currently, a combination of chemotherapy and radiotherapy is the standard treatment approach for locally advanced non-small cell lung cancer (NSCLC). However, the clinical outcomes are still disappointing, with the 5-year survival rate being only approximately 20%. Further improvement in treatment outcome for patients with locally advanced NSCLC will require the development of more effective combined-modality therapies. Increasing attention has focused on the integration of targeted agents into current therapies. Many preclinical studies in this area have targeted the epidermal growth factor receptor (EGFR) signaling pathway to increase radiosensitivity. The in vitro rationale for targeting EGFR and concurrent ionizing radiation is well established, but to date, rare clinical data could provide proof-of-principle. In this review article, we briefly discuss pre-clinical data and the rationale and report all the different published clinical trials focusing on efficacy and toxicity in order to clarify and to summarize the present state-of-the-art of this particular combination in NSCLC.     

ZD1839 (Iressa) in non-small cell lung cancer

Despite the advent of cisplatin-based combination chemotherapy for advanced non-small cell lung cancer (NSCLC), the prognosis for this patient population remains poor. Novel biologically targeted agents currently in development have the potential for greater efficacy against NSCLC, and possibly less toxicity than is associated with conventional cytotoxic chemotherapy. The epidermal growth factor receptor (EGFR) is recognized as a potentially useful target, and the small molecule, orally active EGFR-tyrosine kinase inhibitor ZD1839 (Iressa) is currently the furthest along in clinical development of the anti-EGFR agents. This review summarizes the currently available clinical data on the use of ZD1839 in the treatment of NSCLC.     

Successful treatment using apatinib with or without docetaxel in heavily pretreated advanced non-squamous non-small cell lung cancer: A case report and literature review

Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC. Moreover, addition of anti-angiogenic agents to chemotherapy showed robust efficacy in advanced NSCLC, regardless of tumor histology. Here, we present the case of a heavily pretreated lung adenocarcinoma patient who was treated with apatinib and apatinib continuation plus docetaxel re-challenge. He was negative for several driver genes, including EGFR, ALK, KRAS, ROS1, HER2, RET and BRAF. The previous treatment included platinum-based doublets, pemetrexed monotherapy, docetaxel plus bevacizumab, gefitinib monotherapy, nab-paclitaxel monotherapy, irinotecan plus oxaliplatin and radiotherapy. He obtained a partial response after both apatinib monotherapy and apatinib plus docetaxel treatment, with progression-free survival durations of 5 months and 6 months, respectively. This case indicated that apatinib monotherapy or apatinib plus docetaxel might be regarded as a therapeutic option for heavily pretreated patients with advanced non-squamous NSCLC.     

Should progression-free survival be the primary measure of efficacy for advanced NSCLC therapy?

Non-small-cell lung cancer (NSCLC) is a leading cause of malignancy-related mortality in the Western world. Despite advances in early detection and standard treatment, NSCLC is frequently diagnosed at an advanced stage and therefore patients have a poor prognosis. However, its heterogeneity provides ample opportunity for multiple treatment approaches and target pathways. Considerable progress has been made in identifying novel targets, leading to a growing number of treatment options. Overall survival (OS) may not always be the most appropriate primary end point for assessment of efficacy, as it is likely that patients with NSCLC will receive multiple lines of therapy during their treatment. Additionally, crossover appears as an ethical necessity to many investigators if molecular targeted agents display outstanding early efficacy. While improving OS remains the goal for clinicians, progression-free survival (PFS) is increasingly being utilised as an alternative end point. In this article, we will evaluate the value of PFS as a primary measure of efficacy for advanced NSCLC, compare the clinical situation with that in other solid malignancies and review the growing number of treatment options for NSCLC.     

Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer

Despite the optimization of chemotherapy regimens, treatment outcomes for advanced non-small cell lung cancer (NSCLC) are still considered to be disappointing. Thus, clinical research of new treatment strategies is warranted. Several targeted agents have been introduced into clinical trials in NSCLC, but to date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. One of the main reasons for the failure of several clinical trials of targeted therapy in lung cancer is that there is multilevel cross-stimulation among the targets of the new biological agents along several pathways of signal transduction that lead to neoplastic events; blocking only one of these pathways, as most first-generation targeted agents do, allows others to act as salvage or escape mechanisms for cancer cells. Sorafenib and sunitinib are two oral multitargeted receptor tyrosine kinase inhibitors. Sorafenib is a multikinase inhibitor that inhibits the kinase activity of both C-RAF and B-RAF and targets the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and stem cell factor receptor [KIT]). Sunitinib is a multitargeted inhibitor of PDGFR, KIT, fms-like tyrosine kinase 3, and VEGFR. The kinases targeted and inhibited by sorafenib and sunitinib directly and indirectly regulate tumor growth, survival, and angiogenesis, and this might be expected to result in broad antitumor efficacy. Sorafenib and sunitinib have been approved by the U.S. Food and Drug Administration for the treatment of metastatic renal cell carcinoma; sunitinib has also been approved for the treatment of gastrointestinal stromal tumors. Their mechanism of action, preclinical data, and phase II studies suggest efficacy in the treatment of advanced NSCLC.     

晚期非小细胞肺癌的中医维持治疗

晚期非小细胞肺癌（ＮＳＣＬＣ）维持治疗是肿瘤学专家在化疗疗效达到“瓶颈”后为延长患者生存时间所提出的一种新型治疗模式,主要包括化疗维持和靶向维持,目前维持治疗尚存在较多的争议,临床上尚未完全推行。本文通过论述中医药治疗晚期ＮＳＣＬＣ的现状及优势,分析中医药进行维持治疗的优势及可行性,并对维持治疗的发展进行探索,希望中医药在晚期ＮＳＣＬＣ维持治疗中能有新的突破和进展。