Non-surgical therapy for patients with advanced non-small cell lung cancer

Abstract Non-small cell lung cancer is the major cancer problem in the Western World. Treatment and prognosis are highly stage dependent, although overall only 5–10% of patients will be alive 5 years after diagnosis. Patients with early stage disease are treated with surgery alone. However, for patients with locally advanced disease there is increasing evidence that combined modality approaches, incorporating chemotherapy, radiotherapy and/or surgery result in modest improvements in survival. For patients with metastatic non-small cell lung cancer there is evidence from metaanalyses and randomised studies that chemotherapy results in improvements in both duration and quality of life. Despite these advances, there is substantial room for further improvement and therefore, wherever possible, patients should be enrolled in well designed clinical studies.     

Non-surgical therapy for the patients with advanced non-small cell lung cancer

Abstract Radiation therapy (RT) and chemotherapy have been the two main treatment modalities for advanced non-small cell lung cancer (NSCLC). New techniques in RT, including hyperfractination and 3-dimensional conformal RT (3-DCRT), have changed conventional RT, which has been regarded as standard modality for locally advanced NSCLC. Introduction of cisplatin into chemotherapeutic regimens for NSCLC has changed the status of chemotherapy to standard therapy for patients with stage IV or stage IIIb with effusion. Radiation therapy or chemotherapy alone have already showed their limitations, even although they could improve the survival of NSCLC patients. Combined treatments with these two have become powerful alternatives for patients with unresectable and locally advanced NSCLC. Sequential or concurrent chemoradiotherapy could improve the response rate and survival rate without a remarkable increase in toxicities. Gene therapy is a novel therapeutic approach based on molecular oncology and tumour immunology. The practical contribution of gene therapy to clinical oncology is still minimal. From the research data, gene therapy has shown its potential to become a new treatment modality or to lead us to as yet undiscovered novel approaches to the treatment of lung cancer.     

晚期非小细胞肺癌脑转移的靶向治疗

脑转移是非小细胞肺癌(NSCLC)常见的转移部位,出现脑转移的患者生活质量下降,预后不佳.目前脑转移的主要治疗方式为全脑放疗,常规化疗对脑转移治疗效果不佳.近期多个个案报道和小规模的回顾性研究发现以吉非替尼和厄洛替尼为代表的表皮生长因子受体-酪氨酸激酶抑制剂对NSCLC脑转移体现出良好治疗效果.特别是对于存在表皮生长因子受体基因突变的患者,效果更加显著.提示该类药物可能是治疗NSCLC脑转移的一个好选择.     

Management of advanced non-small cell lung cancer: current trends

Carcinoma of the lung continues to be the leading cause of cancer-related deaths for Americans. Major efforts have been made in the treatment of advanced non-small cell lung cancer; chemotherapy and investigations in the last decade have yielded a number of new agents and combinations. Despite progress with newer agents for the treatment of non-small cell lung cancer, only 14% of patients with the disease are alive 5 years after the initial diagnosis. Toward improving the outcome of patients with advanced non-small cell lung cancer, a few trends can be identified. These include further work on combination chemotherapy, the introduction of novel biologic agents into treatment, and predicting which patients will respond to chemotherapy. These trends are discussed in this review.     

Current and emerging medical treatments for non-small cell lung cancer: a primer for pulmonologists

Pulmonary physicians commonly develop relationships with lung cancer patients through the evaluation and staging of the disease prior to the discussion of treatment options with oncologists. Given the relationship that develops, a pulmonologist is often asked about aspects of the treatment plan that may be slightly outside of their comfort zone. The aim of this overview of medical treatment of non-small cell lung cancer is to provide the pulmonologist with an overview of the evidence guiding current practice so that they can be more comfortable answering their patients' questions while awaiting the expert opinion of the oncologist. We discuss standard chemotherapeutic agents, their common side effects, and their use in the adjuvant and neoadjuvant setting, as definitive therapy for locally advanced disease, as palliative therapy for advanced disease, and as maintenance therapy. We also discuss the mechanisms of action and side effects of targeted therapies (including inhibitors of vascular endothelial growth factor [VEGF], epidermal growth factor receptor [EGFR] signaling and the anaplastic lymphoma kinase [ALK] protein), their currently accepted uses, and upcoming phase III trials, the results of which may influence standard practice.     

Evidence-based outcomes for patients with advanced non-small cell lung cancer

A majority of patients diagnosed with non-small cell lung cancer (NSCLC) will have advanced disease at diagnosis. In the past, systemic therapy (chemotherapy) has demonstrated only slight improvement in survival, hence, practitioners were reluctant to refer patients for cytotoxic therapy. In the past few years, newer chemotherapeutic agents, with increased activity against NSCLC, have been shown to significantly improve median and 1-year survival rates and improve quality of life. Although advanced NSCLC is considered incurable disease, it is, however, potentially treatable disease. This chapter will address the evidence regarding currently available therapies for patients with advanced stage NSCLC.     

非小细胞肺癌的个体化治疗与耐药分子指标的检测

近年研究表明,细胞信号转导中相关因子如蛋白激酶C、PI3-K/Akt、核转录因子及表皮生长因子等的表达异常,肿瘤细胞DNA修复的异常及其它相关基因如β-微管基因突变及β微管蛋白同型表达的改变、核苷酸还原酶基因的异常表达及多态性、肿瘤基因stathmin的表达异常与非小细胞肺癌（non-small cell lung cancer,NSCLC）耐药的产生也存在密切联系。耐药分子指标的检测不仅可以更深入地明确临床NSCLC患者的耐药机制,而且可为NSCLC患者的个体化治疗、耐药的逆转研究及分子靶向治疗等提供重要参考依据。     

Weekly paclitaxel for advanced non-small cell lung cancer patients not suitable for platinum-based therapy

Platinum-based combinations are efficacious in the treatment of advanced non-small cell lung cancer (NSCLC) but their toxicity makes them unsuitable for elderly and for patients with co-morbidities. We assessed the efficacy and toxicity of low-dose of paclitaxel in patients who were elderly or who had contraindications against cisplatin therapy. Seventy-one patients (median age 68; range 42-82 years) with unresectable NSCLC were treated with weekly paclitaxel (80 mg/m2) infusion (1 h) for several cycles without intervening rest periods. Thirty-seven patients had PS 1 and 34 had PS 2 status. A total of 614 courses were administered (median 9, range 2-20). There were no episodes of grade 4 toxicities and only 1 patient had grade 3 thrombopenia. Grade 3 anemia or neutropenia were not observed and severe non-hematological toxicity was uncommon: grade 1-2 fatigue in 52%; grade 1-2 motor neuropathy in 42% and grade 3 in 5.5%; grade 1-2 sensory neuropathy in 46.3% of patients. Twenty-seven of the 67 evaluable patients (40.3%) had an objective response, whereas 26 patients (38.8%) had stable disease. The median overall survival for the entire group was 8.4 months (95% CI = 5.6 to 11.2) and the 1-year and 2-year survival was 37.4% and 12.1%, respectively. The median time-to-progression was 5.4 months (95% CI = 3.3 to 7.4). Our data show that low-dose weekly paclitaxel is active and well tolerated in this group of patients with NSCLC and poor prognosis and, as such, is useful for patients in whom platinum-based combinations are not suitable.     

Accelerated dose escalation with proton beam therapy for non-small cell lung cancer

Local tumor control remains challenging in many cases of non-small cell lung cancer (NSCLC), particularly those that involve large or centrally located tumors. Concurrent chemotherapy and radiation can maximize tumor control and survival for patients with locally advanced disease, but a substantial proportion of such patients cannot tolerate this therapy, and sequential chemoradiation regimens or radiation given alone at conventionally fractionated doses produces suboptimal results. An alternative approach is the use of hypofractionated proton beam therapy (PBT). The energy distribution of protons can be exploited to reduce involuntary irradiation of normal tissues, particularly the low-dose irradiation problematic in intensity-modulated (photon) radiation therapy (IMRT). Here we summarize current evidence on the use of hypofractionated PBT for both early-stage and locally advanced NSCLC, and the possibility of using hypofractionated regimens for patients who are not candidates for concurrent chemotherapy.KEYWORDS : Hypofractionation, early-stage disease, locally advanced disease, proton beam therapy (PBT), stereotactic ablative body radiation (SABR), intensity-modulated proton therapy (IMPT), passive scattering, dosimetric comparisons, clinical studies     

MEK抑制剂治疗非小细胞肺癌的研究进展

随着对肿瘤分子机制的深入研究,非小细胞肺癌的分子靶向治疗已获得重大进展。蛋白激酶抑制剂是新近研发的靶向药物之一,其通过阻碍细胞内分子传导,影响肿瘤细胞的生存与增殖而起作用。丝裂原细胞外激酶（mitogenextracellularkinase,MEK）在Ras／Raf／MEK／ERK信号通路中发挥重要作用,大量的基础及临床研究提示MEK广泛作用于多种信号通路并在各类实体肿瘤中过度表达,因此MEK抑制剂可能具备广谱的抗肿瘤的优势。本文以新型MEK抑制剂司美替尼（selumetinib,AZD6244,ARRXY-142886）为例,重点阐述Ras／Raf／MEK／ERK信号通路、MEK抑制剂的作用机制及研究进展。     

Evidence-based outcomes for patients with non-small cell lung cancer undergoing resection

Surgery plays a vital role in the management of Stages I-IIIa NSCLC. Careful patient selection and improved perioperative care now allow pulmonary resection to be performed with a very low morbidity and mortality even in older patients, or in patients undergoing pneumonectomy or extended operations. Most patients with Stage IIIb disease are not candidates for surgery, but resection can be curative for highly selected groups of patients with T4 tumors when these are not associated with nodal metastases. Surgery in conjunction with induction chemotherapy or chemoradiation has become a standard approach to the management of Stage IIIa (N2) disease and, in that setting, can be performed safely and effectively. The role of surgical resection in the treatment of NSCLC will undoubtedly continue to evolve as we gain a better understanding of the biology and multimodality therapy of this disease.     

Photodynamic therapy for the treatment of non-small cell lung cancer

Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.     

培美曲塞维持治疗晚期非小细胞肺癌的Meta分析

目的本研究旨在对培美曲塞维持治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性进行分析。方法计算机检索PubMed、Medline、Embase、维普、中国期刊全文数据库等数据库,收集培美曲塞单药维持治疗对比最佳支持治疗(BSC)Ⅲb及Ⅳ期非小细胞肺癌的随机对照试验,用Cochrane协作网提供的Revman 5软件对数据进行Meta分析。结果共纳入3个随机对照研究(RCT),共1 257例患者。Meta分析结果显示:与对照组相比,培美曲塞维持治疗组能提高患者疾病控制率(DC)(OR=1.95,95%CI:1.52².50,P<0.000 01),且纳入研究均显示,培美曲塞维持治疗在无进展生存期(PFS)及总生存期(OS)方面也有积极意义。培美曲塞维持治疗组G3/4级不良反应均少见,其中乏力、恶心呕吐及贫血有统计学差异(P<0.05),而粒细胞减少无统计学差异(P=0.35)。结论培美曲塞维持治疗对比最佳支持治疗晚期NSCLC,可显著提高疾病控制率、延长无进展生存期及总生存期,并且严重不良反应少见。