沙利度胺联合昂丹司琼预防肺癌化疗所致恶心呕吐的临床研究

目的:探讨沙利度胺联合昂丹司琼对肺癌患者接受含顺铂双药方案化疗所致恶心呕吐的有效性和安全性。方法:将 2014年2月至2016年2月我院肿瘤科收治的60 例肺癌患者随机分成试验组(30例)和对照组(30例),均采用含顺铂25mg/m2 d1~3双药方案化疗。对照组用昂丹司琼注射液8mg qd d1~3化疗前30min 静脉滴注,试验组在对照组基础上加用沙利度胺片100mg口服 d1~5。结果:试验组和对照组急性恶心控制的有效率为 90% vs 80%,完全缓解率为73% vs 67%,差异均无统计学意义(P均＞0.05)。试验组和对照组第2~5天延迟性恶心控制的有效率分别为:87% vs 53%（P=0.011）,80% vs 47%（P=0.016）,80% vs 50%（P=0.030）,87% vs 74%（P=0.331）。试验组和对照组第2~5天延迟性恶心完全缓解率分别为:67% vs 37%（P=0.039）,57% vs 27%（P=0.036）,60% vs 23%（P=0.009）,67% vs 40%（P=0.070）。试验组和对照组急性呕吐控制的有效率为93% vs 90%,完全缓解率为84% vs 77%,差异均无统计学意义(P均 ＞0.05)。试验组和对照组第2~5天延迟性呕吐控制的有效率分别为:90% vs 73%（P=0.182）,83% vs 70%（P=0.360）,87% vs 73%（P=0.333）,94% vs 80%（P=0.255）。试验组和对照组第2~5天延迟性呕吐完全缓解率分别为:76% vs 46%（P=0.034）,66% vs 33%（P=0.020）,70% vs 40%（P=0.038）,73% vs 50%（P=0.110）。试验组和对照组的不良反应均可耐受,镇静、嗜睡、乏力、便秘、头痛和皮疹的发生率差异均无统计学意义(P均＞0.05)。结论:沙利度胺联合昂丹司琼能有效预防肺癌患者含顺铂双药化疗引起的恶心呕吐,能提高延迟性恶心呕吐的控制率,未增加特殊不良反应,安全性较好,是可供选择的止吐药物。     

蛋白质组学及其研究技术在肺癌分子生物标志物研究中的应用

肺癌是全球发病率和死亡率较高的恶性肿瘤。细胞从正常状态转变为肿瘤的过程中，细胞内蛋白质表达谱必然会发生一系列变化，肿瘤分子标记物就是细胞在非正常状态下产生的分子．以高通量结合生物信息学为特点的蛋白质组学分析技术可以从细胞整体水平上检测到这种变化近年来，为了降低肺癌的死亡率并提高其治疗效果，研究人员利用这一新的手段如利用激光捕获显微切割技术和双相凝胶电泳结合基质辅助激光解析电离飞行时间质谱（MALDI-TOF MS）和表面增强激光解析电离色行时间质谱（SELDI—TOF MS）寻找有效的肺癌标记物。本文对蛋白质组学技术在肺癌生物标志物研究中的应用作了综述。     

A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.     

Effect of thalidomide on colorectal cancer liver metastases in CBA mice

BACKGROUND AND AIMS: Thalidomide has undergone resurgence in the treatment of specific malignancies. One of the possible actions of thalidomide may be an antiangiogenic effect. This study investigates the effects of thalidomide on tumor growth and long-term survival in a murine model of colorectal liver metastases. METHODS: Liver metastases were produced in male CBA mice by intrasplenic injection of a dimethyl hydrazine induced MoCR colon cancer murine cell line. Thalidomide was administered daily at doses ranging from 50 to 300 mg/kg by intraperitoneal injection. Tumor growth was assessed using quantitative stereological analysis. The effect on long-term survival was determined at the maximum tolerated dose using Kaplan-Meier analysis. The microvascular effects of thalidomide were assessed by laser Doppler flowmetry (LDF) and microvascular resin casting. Immunohistochemistry was used to determine vascular endothelial growth factor (VGEF) and basic fibroblast growth factor (bFGF) expression. RESULTS: Thalidomide, (50-300 mg/kg) caused no significant reduction in tumor growth by day 21 following induction of liver metastases and caused systemic toxicity at a dose of 300 mg/kg. At a dose of 200 mg/kg given beyond 35 days, thalidomide significantly reduced tumor growth compared to control, (P = 0.029). No significant impact on survival was however observed (P = 0.93). LDF and microvascular resin casting showed no differences in blood flow or tumor microvascular architecture. VGEF and FGF were expressed in tumors, but remained unaltered by thalidomide administration compared to matched controls. CONCLUSIONS: Thalidomide caused a significant reduction in the volume of colorectal liver metastases during the late phase of tumor growth. There was however no improvement in survival. Tumor growth reduction in this model did not appear to be due to microvascular changes or altered expression of VGEF or basic FGF. Further investigation into potential mechanisms of action of thalidomide and its synergistic use with other therapies is required.     

Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first-line, systemic chemotherapy

BACKGROUND: Few studies have assessed formally whether treatment outcomes have improved substantially over the years for patients with advanced nonsmall cell lung cancer (NSCLC) enrolled in Phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS: The literature was searched to identify trials that addressed the role of chemotherapy regimens in the first-line setting for the treatment of advanced NSCLC. Trends were tested by using multiple regression analysis. RESULTS: In total, 121 Phase III trials were identified that involved 42,768 patients with 263 chemotherapy arms and 11 best supportive care (BSC) arms, all of which were initiated between 1982 and 2002. Although the number of randomized patients and the proportion of patients with metastatic disease had increased over the years, the number of patients with a poor performance status who were accrued into the trials had decreased. Cisplatin-based chemotherapy was been investigated most frequently during the period. The multiple regression analysis revealed a significant improvement in median survival and in the median time to disease progression over the years, with annual prolongations of 0.1203 months (3.609 days) and 0.0617 months (1.851 days), respectively (P< .0001 and P < .0130, respectively). In addition, the use of cisplatin and carboplatin was associated significantly with survival prolongation. The median survival for patients who received BSC also increased progressively over the years (P = .0487). CONCLUSIONS: The survival of patients with NSCLC in Phase III trials improved slowly but steadily over time, although the main factors responsible for this improvement remain unknown. Nonetheless, the current results also suggested that novel targets and new agents will be required in the future fight against advanced NSCLC.     

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.     

An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer

The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.     

Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: meta-analysis of phase III trials

Background

Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations.

Methods

We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria - non-smokers with adenocarcinomas - associated with increased likelihood of EGFR mutations.

Results

Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64 years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p < 10⁻¹⁵), as well as improved progression-free survival (PFS; hazard ratio 0.45, p < 10⁻¹⁶). Overall survival (OS) was not significantly different between treatment groups (p = 0.35).

Conclusions

This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice.     

循环miRNAs在肺癌诊断和治疗中的研究进展

肺癌是全世界男性和女性癌症死亡的第一原因。尽管近些年对癌症信号通路的了解和在新的治疗方法开发上有了新进展,但是肺癌的不良预后和高复发率依然存在。循环miRNAs在许多实体瘤（如肺癌）中,可作为稳定表达的非侵入性诊断标志物。一些miRNAs异常可能与肿瘤细胞常规化疗的耐药性有关,影响着肿瘤细胞的药物敏感性。这些miRNAs的调控,通过使用miRNAs类似物,可以调节关键基因网络和信号通路,通过抑制肿瘤细胞增殖来提高抗癌治疗的疗效,增加药物敏感性。因此,miRNAs疗法提供了新的抗肿瘤方法:更有效的个性化治疗、提高药物疗效、预测不同抗癌药物的反应。本综述的目的是为肺癌循环miRNA提供一个作为潜在诊断生物标志物、大规模临床筛选诊断的可行性评估以及miRNAS抗癌耐药机制对肺癌的治疗的概述。最后,miRNA分析的局限性和潜在性需要今后进一步探索。     

Prognostic value of nonangiogenic and angiogenic growth patterns in non-small-cell lung cancer

An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P<0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117-2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169-3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage.     

Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials

Background  

Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer (NSCLC) is based on large randomized controlled trials. The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials.     

Front-line paclitaxel and topotecan chemotherapy in advanced or metastatic non-small-cell lung cancer: a phase II trial

Purpose: Based on previous experience, we combined topotecan with paclitaxel (weekly administration) in patients with non-small-cell lung cancer (NSCLC). Our primary objective was to determine the response rate and survival and our secondary objective, the safety of the regimen. Methods: From October 2003, until March 2005, 45 patients all with histologically or cytologically confirmed NSCLC were enrolled. All patients were chemotherapy and radiotherapy naive. Both agents were infused on day 1 of every week once for three consecutive weeks, every 28 days. Three infusions were considered as one course. The treatment plan was to give three courses (nine infusions) and then to evaluate the response. Topotecan (1.75 mg/m²) was infused for 30 min and paclitaxel (70 mg/m²) for 90 min; these doses had been established as the maximum tolerated dose in a previous phase I–II trial. Results: Eighteen/45 (40%) patients responded, 2 (4.4%) complete responses and 16 (35.6%) partial responses. Twenty-one (46.7%) patients had stable disease, and 6 (13.3%) disease progression. The median duration of response was 8 months and median time to tumor progression 9 months. Grade 3 and 4 neutropenia was observed in two patients (in these two patients, the dose of both drugs was reduced by 25% and G-CSF was given), grade 4 thrombocytopenia in one patient and grade 4 anemia in one patient. Conclusion: This novel combination of topotecan–paclitaxel in a weekly administration rendered a 40% response rate, with very low toxicity in stages IIIA, IIIB and IV NSCLC patients.     

A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics.

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.     

A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer.

PURPOSE: The aim of this study was to determine the role of chemotherapy dose intensity in patients with initially unresectable non-metastatic non-small-cell lung cancer (NSCLC), with survival as primary end point, by testing two different regimens as induction chemotherapy followed by thoracic irradiation. PATIENTS AND METHODS: Patients had pathologically proven NSCLC, an initially unresectable non-metastatic tumour without homolateral malignant pleural effusion, no prior history of malignancy and had received no prior therapy. Treatment was randomised for chemotherapy between three courses of MIP (mitomycin C 6 mg/m2; ifosfamide 3 g/m2; cisplatin 50 mg/m2) or SuperMIP (mitomycin C 6 mg/m2; ifosfamide 4.5 g/m2; cisplatin 60 mg/m2, carboplatine 200 mg/m2), followed by chest irradiation (60 Gy; five times per week, for 6 weeks). If the tumour became resectable after chemotherapy, surgery was performed, followed by mediastinal irradiation. RESULTS: A total of 351 patients were eligible: 176 in the MIP arm and 175 in the SuperMIP arm, with 43% and 51% stages IIIA and IIIB, respectively. There was a significantly higher objective response rate with SuperMIP (46%) compared with MIP (35%) (P=0.03) [95% confidence interval (CI) for the difference between the response rates, 1% to 22%]. After induction chemotherapy, surgery was performed in 54 (15%) patients (27 per arm) and chest irradiation in 203 (57%) patients (102 in the MIP arm and 101 in the SuperMIP). In terms of survival, there was no statistically significant difference between the two study arms (P=0.16), with median survival times of, for MIP and SuperMIP, respectively, 12.5 (95% CI 10.1-14.9) and 11.2 (95% CI 9.7-12.8) months. Haematological toxicity and dosage reductions were higher with SuperMIP, which was nevertheless associated with a significantly increased absolute dose intensity. CONCLUSIONS: High dose-intensity induction chemotherapy does not improve survival in initially unresectable non metastatic NSCLC.     

Elevated progesterone receptor membrane component 1/sigma-2 receptor levels in lung tumors and plasma from lung cancer patients

Cancer is one of the leading causes of death, and there is an urgent need for new biomarkers and therapeutic targets. The progesterone receptor membrane component 1 (Pgrmc1) protein is upregulated in multiple types of cancer, and Pgrmc1 is required for tumor cell proliferation, motility and tumor formation in vivo. Furthermore, a small molecule inhibitor of Pgrmc1 suppressed the growth of lung, breast and cervical cancer cell lines. Recently, Pgrmc1 was identified as the sigma-2 receptor, a putative type of opioid receptor, and sigma-2 receptors are induced in cancers. However, Pgrmc1 shares no homology with known opioid or hormone receptors but is related to cytochrome b(5), and Pgrmc1 binds to heme and has reducing activity. In this study, we have analyzed Pgrmc1 levels in clinical tumor samples from squamous cell lung cancers (SCLC) and lung adenocarcinomas compared to corresponding nonmalignant tissue. Pgrmc1 levels increased significantly (p ≤ 0.05) in 12/15 SCLC samples and was elevated in poorly differentiated tumors. Pgrmc1 was highly expressed in SCLC cell lines, and SCLC cell survival was inhibited by siRNA knockdown of Pgrmc1 or the Pgrmc1 inhibitor AG-205. In adenocarcinomas, 6/15 tumors significantly had elevated Pgrmc1 levels, which correlated with patient survival. Pgrmc1 localizes to secretory vesicles in cancer cells, and Pgrmc1 was secreted by lung cancer cells. Furthermore, Pgrmc1 was significantly elevated in the plasma of lung cancer patients compared to noncancer patients. Together, the results demonstrate that Pgrmc1 is a potential tumor and serum biomarker, as well as a therapeutic target, for lung cancer.     

反应停、紫杉醇对Lewis肺癌小鼠的抑瘤作用

目的　研究反应停、小剂量紫杉醇对 L ewis肺癌小鼠皮下移植瘤和肺转移瘤的抑制作用 ,并探讨其与肿瘤细胞凋亡和细胞周期的关系。方法　 50只荷 L ewis肺癌小鼠随机分为四组 ,分别给予生理盐水、反应停、小剂量紫杉醇、反应停联合小剂量紫杉醇治疗 ,第 2 1天处死动物 ,称取鼠重、瘤重、肺重 ,计数肺转移结节数 ,免疫组化染色记数肿瘤组织微血管密度 ,流式细胞仪检测肿瘤细胞凋亡率及细胞周期。结果　反应停、小剂量紫杉醇单独及联合治疗组肿瘤重量与对照组间差异无显著性 (P>0 .0 5)。反应停、小剂量紫杉醇单独及联合治疗组肺重、肺转移结节数及肿瘤组织微血管密度均小于对照组 ,差异有显著性 (P<0 .0 5)。各治疗组肿瘤细胞凋亡率及 G1、S、G2 期肿瘤细胞百分数与对照组间差异无显著性 (P>0 .0 5)。结论　反应停、小剂量紫杉醇不能抑制 L ewis肺癌皮下移植瘤生长 ,但可抑制肿瘤肺转移 ,两药间无协同或拮抗作用。反应停、小剂量紫杉醇不诱导 L ewis肺癌细胞凋亡 ,不影响肿瘤细胞生长周期     

局限期小细胞肺癌化疗及联合放化疗的远期疗效观察

目的　观察单纯化疗及放射治疗联合化疗对局限期小细胞肺癌的疗效以及不同放射治疗剂量对疗效的影响。方法　回顾性分析黑龙江省肿瘤医院 1988年 2月至 1998年 3月收治的经病理证实的局限期小细胞肺癌 12 8例 ,单纯化疗 42例 ,同步放化疗 3 8例 ,交替放化疗 48例。放疗总剂量≤ 45Gy 2 0例 ,≥60Gy2 3例 ,>45Gy且 <60Gy 43例。 结果　同步治疗组、交替治疗组和单纯化疗组的 3年生存率分别为2 3 .7%、2 0 .8%和 4.8% ,同步治疗组和交替治疗组分别与单纯化疗组比较 ,差异均有显著性 (P <0 .0 5 ,P <0 .0 5 ) ,同步治疗组与交替治疗组之间 ,无显著性差异 (P >0 .0 5 )。胸部照射≤ 45Gy和≥ 60Gy剂量组的 2年局部复发率分别为 5 5 .0 %和 8.7% ,有显著性差异 (P <0 .0 1)。结论　化疗联合放射治疗能提高局限期小细胞肺癌患者的生存期。局部复发率与胸部照射剂量有密切关系。     

Blood‐based detection of lung cancer using cysteine‐rich angiogenic inducer 61 (CYR61) as a circulating protein biomarker: a pilot study

Lung cancer is the most often diagnosed cancer and the main cause of cancer deaths in the world compared with other tumor entities. To date, the only screening method for high‐risk lung cancer patients is low‐dosed computed tomography which still suffers from high false‐positive rates and overdiagnosis. Therefore, there is an obvious need to identify biomarkers for the detection of lung cancer that could be used to guide the use of low‐dosed computed tomography or other imaging procedures. We aimed to assess the performance of the protein cysteine‐rich angiogenic inducer 61 (CYR61) as a circulating biomarker for the detection of lung cancer. CYR61 concentrations in plasma were significantly elevated in 87 lung cancer patients (13.7 ± 18.6 ng·mL⁻¹) compared with 150 healthy controls (0.29 ± 0.22 ng·mL⁻¹). Subset analysis stratified by sex revealed increased CYR61 concentrations for adenocarcinoma and squamous cell carcinoma in men compared with women. For male lung cancer patients versus male healthy controls, the sensitivity was 84% at a specificity of 100%, whereas for females, the sensitivity was 27% at a specificity of 99%. The determination of circulating CYR61 protein in plasma might improve the detection of lung cancer in men. The findings of this pilot study support further verification of CYR61 as a biomarker for lung cancer detection in men. Additionally, CYR61 is significantly elevated in women but sensitivity and specificity for CYR61 are too low for the improvement of the detection of lung cancer in women.     

A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m² d1) and either cisplatin (75 mg/m² d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed–platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations.