Management of patients with advanced non-small-cell lung cancer

Lung cancer is one of the most lethal cancers, causing more deaths of men and women than any other cancer in the United States. Non-small-cell lung cancers account for most the newly diagnosed cases of lung cancer. Many patients with non-small-cell lung cancer present with advanced-stage disease and are not appropriate candidates for combined modality therapy. Although these patients have incurable disease, they have a chance of achieving improved 1-year survival rates and palliation of symptoms with chemotherapy. The performance status of patients with advanced non-small-cell lung cancer is the most important determinant of response to chemotherapy.     

老年人晚期非小细胞型肺癌适形放疗的临床研究

目的 探讨老年人晚期非小细胞型肺癌适形放射治疗的价值。方法 对24例老年晚期非小细胞型肺癌患者实施适形放疗，进行低姑息性达根治剂量的治疗。结果 全组1、2、3年的生存率分别是：91．67％、54．16％、43．33％；放疗期间无急性放射性肺炎发生；统计分析显示：治疗前是否合并上腔静脉综合征、肿瘤体积大小、治疗前后生活质量(KPS)评分、适形放疗剂量为有意义的预后因素。结论 适形放疗对老年人晚期非小细胞型肺癌有治疗意义。     

吉西他滨联合铂类治疗晚期非小细胞肺癌的临床分析

目的评价吉西他滨联合不同铂类化疗药物治疗ⅢB～Ⅳ期非小细胞肺癌（NSCL）的临床疗效和毒副反应。方法45例经细胞学或病理学证实ⅢB～Ⅳ期NSCLC患者（初治35例,复治10例）,患者的预计生存时间均超过2个月。按三种方案联合化疗：（1）吉西他滨＋顺铂（GEM／DDP）,每3周重复1次;（2）吉西他滨＋卡铂（GEM／CBP）,每3周重复1次;（3）吉西他滨＋顺铂（GEM／DDP）,每4周重复1次。按美国癌症研究所（NCI）实体瘤疗效评价标准（Recist标准）对目标病灶评价,毒性反应按2007中国肺癌临床指南（NCI—CTCV2．0）标准进行评价。随访患者中位生存时间并计算1年生存率。结果共完成158个周期全身化疗,平均每个病人接受3．5个周期化疗。吉西他滨联合顺铂3周及4周方案、吉西他滨联合卡铂三种方案的有效率分别为45．8％（11／24）、45．5％（5／11）和50％（5／10）,总有效率为46．7％（21／45）,35例初治患者中有效18例,有效率51．4％,10例复治患者中有效3例,有效率30％。毒副反应主要为白细胞减少、血小板减少、消化道反应、皮疹和搔痒。中位生存时间（MST）为8．9个月,1年生存率为38．7％。结论吉西他滨联合铂类化疗药物治疗晚期NSCL疗效较好,且毒性反应少,耐受性好。     

Targeted therapy in advanced non-small-cell lung cancer

Molecularly targeted therapies have recently expanded the options available for patients with advanced non-small-cell lung cancer (NSCLC). Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathway. The former has emerged as a key regulator of cancer cell proliferation and invasion, and several EGFR inhibitors have been developed. Erlotinib, a small-molecule inhibitor of the EGFR intracellular tyrosine kinase, has been found to improve survival compared with placebo in previously treated patients with advanced NSCLC and is Food and Drug Administration (FDA)-approved in this setting. Clinical and molecular predictors of response to erlotinib, such as a history of never smoking and EGFR gene mutation or amplification, are presently being evaluated to select patients for earlier therapy with erlotinib. Additional EGFR inhibitors are also being examined in randomized trials. The VEGF pathway, a key mediator of angiogenesis, has become an attractive target in multiple malignancies, including lung cancer. Bevacizumab, a monoclonal antibody to VEGF, received FDA approval for use in advanced non-squamous-cell NSCLC in 2006 after a phase III trial reported a significant survival advantage when bevacizumab was added to standard first-line chemotherapy. Small-molecule inhibitors of the VEGF receptor tyrosine kinase, such as sunitinib and sorafenib, have also shown promise in phase II trials and are being further investigated in phase III studies. Because preclinical data suggest a synergistic effect when VEGF and EGFR inhibitors are combined, the concurrent use of erlotinib and bevacizumab has additionally been evaluated in a phase II trial, with encouraging early results suggesting at least equivalent activity to standard salvage chemotherapy, with less toxicity. Several other novel agents are being examined, including inhibitors of histone deacteylases and the 26S proteosome. Research efforts are currently focusing on tailoring such therapies according to predictive clinical and molecular markers.     

埃克替尼联合放疗治疗晚期非小细胞肺癌的研究进展

研究证实埃克替尼治疗表皮生长因子受体突变的非小细胞肺癌(NSCLC)患者疗效明确,并具有放疗增敏效果。国内有大量的研究表明埃克替尼联合放疗能显著提高NSCLC患者生存时间,特别是对老年患者或脑转移患者,且不良反应较小。因此,埃克替尼联合放疗有可能成为治疗晚期NSCLC患者的有效治疗手段。现对其相关研究进展作一综述。     

Targeted drugs for unselected patients with advanced non-small-cell lung cancer: a network meta-analysis

Background

Currently, targeted therapy has shown encouraging treatment benefits in selected patients with advanced non-small cell lung cancer (NSCLC). However, the comparative benefits of targeted drugs and chemotherapy (CT) treatments in unselected patients are not clear. We therefore conduct a network meta-analysis to assess the relative efficacy and safety of these regimens.

Methods

PubMed, EMBASE, Cochrane Library and abstracts from major scientific meetings were searched for eligible literatures. The odds ratio (OR) for objective response rate (ORR) and safety was used for pooling effect sizes. Bayesian network meta-analysis was conducted to calculate the efficacy and safety of all included treatments. All tests of statistical significance were two sided.

Results

A total of 13,060 patients from 24 randomized controlled trials (RCT) were assessed. The targeted agents included bevacizumab (Bev), gefitinib (Gef), erlotinib (Erl) and cetuximab (Cet). Network meta-analysis showed that Bev + CT had a statistically significantly higher incidence of ORR relative to the other six different treatments, including placebo (OR =6.47; 95% CI, 3.85–10.29), Erl (OR =2.81; 95% CI, 2.08–3.70), CT (OR =1.92; 95% CI, 1.61–2.28), Gef (OR =1.40; 95% CI, 1.10–1.75), Erl + CT (OR =1.46; 95% CI, 1.17–1.80) and Gef + CT (OR =1.75; 95% CI, 1.36–2.22), whereas placebo and Erl were associated with statistically significantly lower incidence of ORR. Trend analyses of rank probability revealed that Bev + CT had the highest probability of being the best treatment arm in term of ORR, followed by Cet + CT. Meanwhile, Cet + CT showed significant severer rash and thrombocytopenia compared with Bev + CT. Gef was probable to be the rank 3 for ORR but was associated with relatively low risk for grade ≥3 toxicities.

Conclusions

Our study suggested that Bev + CT may offer better ORR in the treatment of unselected patients with advanced NSCLC. Future studies will be needed to investigate whether the increase of ORR with targeted drugs would be translated into survival benefits.     

Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials

Background: Elderly patients are underrepresented in chemotherapy trials for advanced colorectal cancer (CRC) and non‐small‐cell lung cancer (NSCLC). However, the change in underrepresentation over time has not been documented. Aims: This study aimed to quantify (i) the change in the median age of patients enrolled in clinical trials for metastatic CRC and NSCLC between 1982–1991 and 1992–2001 compared with the general colorectal and lung cancer population, and (ii) the proportion of trials with an upper age limit for eligibility. Methods: A retrospective review of data from the Victorian Cancer Registry and all large published randomized chemotherapy trials for advanced CRC and NSCLC between 1982 and 2001 was conducted. Results: The median age of patients with CRC enrolled in clinical trials remained constant between the two decades (62.0 and 62.2 years), whereas the median age of the CRC population increased from 68.4 to 70.2 years, increasing the median age difference from 6.4 to 8.0 years. The median age of patients with lung cancer in clinical trials increased from 59.8 to 61.8 years, whereas the median age of the lung cancer population increased from 67.4 to 70.4 years, widening the age difference from 7.6 to 8.6 years. More trials set an upper age limit for eligibility in the first decade than in the second decade for both CRC (51 vs 29%, P = 0.04) and NSCLC (68 vs 41%, P = 0.03). Conclusion: International clinical trials for CRC and NSCLC are becoming increasingly unsuitable for application to Australian patients because of the increasing age discrepancy, despite fewer trials restricting eligibility by age.     

Role of systemic therapy in advanced non-small-cell lung cancer

Increasing evidence supports the investigation of chemotherapy in patients with non-small-cell lung cancer (NSCLC). Randomized studies in patients with stage IV disease have shown increased survival in chemotherapy-treated patients compared to best supportive care and indicate the ability of chemotherapy to alter the natural history of this disease. Randomized studies involving adjuvant and neoadjuvant chemotherapy have also shown encouraging results. These studies and results of recent pilot studies utilizing neoadjuvant chemotherapy and concomitant chemoradiotherapy indicate a potential benefit from the use of chemotherapy in patients with NSCLC and call for its continued intensive investigation in clinical trials.     

Patients preferences in chemotherapy for advanced non-small-cell lung cancer

OBJECTIVE: To determine how Japanese patients with lung cancer weigh potential survival, chemotherapy response rate, and symptom relief against the potential toxicity of different treatments in cancer chemotherapy. METHODS AND PATIENTS: We used a questionnaire describing a hypothetical situation about stage IV non-small-cell lung cancer. Seventy-three patients with lung cancer who had received chemotherapy and 120 patients with other respiratory disease as the control group were asked to rate the minimal benefit that would make two hypothetical treatments acceptable. For "chance of cure," "response but not cure," and "symptom relief," the subjects could give answers from 1% to 100% and for prolonging life could give answers from 1 to 60 months. RESULTS: Patients with lung cancer were significantly more likely than were patients with other respiratory diseases to accept either intensive or less-intensive treatments for a potentially small benefit for "chance of cure," "response but not cure," and "symptom relief". The degree of survival advantage that patients require before accepting cancer treatment with its associated toxicity varied widely. If their lives were prolonged 3 months, 19% and 21% of patients with lung cancer would choose to receive intensive and less-intensive treatment, respectively. When the chance of symptom relief was 70%, 73% of patients with lung cancer were willing to choose intensive chemotherapy. Factor associated with patients' choice of chemotherapy in both groups was age. CONCLUSION: Oncologists must consider the substantial range of attitudes to chemotherapy among patients when making treatment decisions and they must give patients the opportunity to be included in this process.     

New molecular targeted therapies for advanced non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted.     

长春瑞滨联合奥沙利铂治疗晚期非小细胞肺癌的临床观察

目的观察长春瑞滨(NVB)加奥沙利铂(LOHP)治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法经病理组织学或细胞学证实的48例晚期非小细胞肺癌患者,随机分为治疗组25例及对照组23例,分别给予NVB LOHP及NVB CDDP治疗,21天为一个周期,均治疗2周期以上。结果治疗组总有效率为44.0%,对照组总有效率为39.1%(P>0.05)。毒副反应以白细胞降低,胃肠道反应和周围神经炎为主,而～度消化道反应、肾脏损害及心功能下降主要发生在对照组,周围神经炎主要发生在治疗组(P<0.05),但均可耐受。结论长春瑞滨加奥沙利铂与长春瑞滨加顺铂治疗晚期非小细胞肺癌相似,均有较好的近期疗效,而长春瑞滨加奥沙利铂组的毒副反应较轻,临床应用更安全,更适合于老年患者。     

Gemcitabine方案复治晚期非小细胞肺癌

目的：探讨Gemcitabine(健择）与顺铂联合化疗方案复治常规方案无效晚期非小细胞肺癌的临床疗效及其不良反应。方法：健择与顺铂联合方案复治22例晚期晨小细胞肺癌二周期，健择每周期第1、8、15天静脉滴注1000mg/m^2，顺铂每周期第1天静脉滴注100mg/m^2，结果：可评价疗效22例，8例获得部分缓解（PR），总有效率36％，全组均可评价不良反应，约30％分别发生Ⅲ-Ⅳ度的血红蛋白下降，白细胞下降，血小板下降和恶心／呕吐，其他毒副反应均轻度可耐受，结论：健择与顺铂联合方案复治常规方案无效晚期非小细胞肺癌有一定的疗效，毒副作用可耐受，是复治晚期非小细胞肺癌较理想的治疗方案之一。     

Survival outcomes of radiofrequency ablation compared with surgery in patients with early-stage primary non-small-cell lung cancer: A meta-analysis

BackgroundThis study compared the overall survival (OS) of patients with early-stage primary non-small-cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA) versus surgery.MethodsA systematic search was performed in MEDLINE, Embase, Cochrane Central Register, and all available Chinese databases to identify relevant publications from inception to April 2019. This meta-analysis compared hazard ratios (HRs) for OS. A multivariate fixed effects model was used to perform a meta-analysis to compare survival between treatments.ResultsSix retrospective studies were included in the quantitative synthesis. Compared with surgery, RFA was associated with a similar long-term OS. The HRs and 95% confidence intervals (CIs) for 2-, 3- and 5-year OS were 1.74 [0.82, 3.71], 1.15 [0.65, 2.02] and 2.69 [0.41, 17.47], respectively, while those of the pooled data were 1.47 [0.94, 2.32] in patients with early-stage primary NSCLC.ConclusionsRFA did not differ signi?cantly from surgery in terms of the 5-year OS in patients with early-stage primary NSCLC. Randomized, controlled clinical trials are warranted to compare these two treatments.     

中晚期非小细胞肺癌放疗联合热疗84例临床观察

目的观察放疗联合热疗效中晚期非小细胞肺癌（NSCLC）的疗和毒副反应。方法采用放疗联合热疗治疗84例中晚期NSCLC（外周型或转移部位适合热疗）,观察症状改善,近期疗效、远期疗效和毒副反应。结果联合治疗明显改善转移灶引起的症状,可测量病灶全部达到PR以上疗效。而且联合治疗明显改善各种肺癌伴随着症状,所有患者局部疗效达到NC以上,46例PR,4例CR,局控率72％,1年生存率63％,2年生存率26％。毒副反应多以Ⅰ、Ⅱ度为主。结论放疗联合热疗治疗中晚期NSCLC（外周型或转移部位适合热疗）患者完全可以耐受,局控率明显提高,生存率较以往报道有一定的提高。