Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Selection of a patient subgroup with advanced esophageal squamous carcinoma who could benefit from second-line chemotherapy

Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months.     

Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy

BackgroundIn the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC).MethodsAfter four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]).ResultsFollowing first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life.ConclusionsPatients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy.     

Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI withchemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trialsare inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKIand chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods:We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Libraryand Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS),overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis,covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR0.88 [0.68- 1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapyafter first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS(HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05- 2.21], p=0.03). However, combinationtherapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improvedthe ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62- 0.88],p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuationof EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combinationtherapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic andpredictive factors to find the group with the highest benefit of the combination strategy.     

晚期非小细胞肺癌一线化疗疗效与生存关系的分析

背景与目的第三代新药组成的方案在晚期NSCLC一线化疗中使大部分患者能够取得疾病控制(CR PR SD),我们进行了本项回顾性分析以探讨一线化疗疾病控制与疾病未控(PD)患者之间生存的差别,以及疾病控制患者有效(CR PR)和稳定(SD)患者之间生存的差别,明确与患者生存有关的预后因素。方法本项回顾性分析纳入了完成第三代新药组成的铂类或非铂类方案一线化疗的118例IIIB期(伴恶性胸水)/IV期NSCLC患者,一线化疗的疗效按RECIST标准根据影像学结果评价为CR,PR,SD,PD四种情况。结果一线化疗后CR PR SD共86例(72.9%)[其中CR2例(1.7%),PR47例(39.8%),SD37例(31.4%)],PD32例(27.1%)。CR PR SD和PD患者MST有统计学差别,为17.8月和8.4月(P=0.001)。CR PR和SD患者MST无统计学差别,为18.1月和15.5月(P=0.917),中位PFS无统计学差别,为7.1月和6.9月(P=0.622)。Cox多因素回归分析显示分期(IIIB期或IV期)、化疗线程(≤3线或≥4线)、一线化疗疾病是否控制是总生存的独立预后因素。结论本研究结果表明,晚期NSCLC患者一线化疗有效和稳定的患者其生存较进展患者好,疾病稳定患者的生存获益与有效患者无明显差别。     

晚期NSCLC一线化疗疾病控制与生存关系的分析

目的回顾性分析一线化疗疾病控制（DCR）与进展（PD）患者之间生存的差别,探讨DCR可否预测生存。方法本文回顾性分析本院一线含铂联合化疗86例ⅢB期/Ⅳ期非小细胞肺癌（NSCLC）患者,化疗的疗效按WHO标准分为CR,PR,SD,PD。结果一线化疗后DCR共64例（74.4%）[其中CR 0例,PR 30例（34.9%）,SD 34例（39.5%）],PD 22例（25.6%）。DCR和PD患者中位生存期（MST）有统计学意义,为14.2月和5.1月（P〈0.001）。CR＋PR和SD患者MST有统计学意义,为15.0月和11.0月（P=0.030）。COX多因素回归分析显示一线化疗疾病控制（P=0.017）,ECOG评分（P=0.046）是总生存的独立预后因素。结论本研究提示晚期NSCLC患者一线化疗疾病控制患者其生存较进展患者好,疾病控制比化疗有效似乎更能反映化疗疗效,预测生存期。     

GEMOX方案和FOLFOX方案一线治疗晚期十二指肠癌的疗效观察

目的 探讨GEMOX方案和FOLFOX方案一线治疗晚期十二指肠癌的疗效和安全性。方法 回顾分析本院2008年6月至2016年1月收治的30例晚期十二指肠癌患者的临床及随访资料,其中10例未接受化疗,20例接受化疗（GEMOX方案9例、FOLFOX方案11例）,分别采用RECIST 1.1版与NCI-CTC 4.0版标准评价疗效和不良反应,Kaplan-Meier法进行生存分析。结果 GEMOX方案和FOLFOX方案均无CR和PR病例,其中GEMOX方案获SD 6例、PD 3例,疾病控制率（DCR）为66.7％,FOLFOX方案获SD 4例、PD 7例,DCR为36.4％,两组DCR的差异无统计学意义（P＞0.05）。GEMOX方案和FOLFOX方案的中位总生存期（OS）分别为27.9个月和15.2个月（P=0.179）;GEMOX方案的中位无进展生存期（PFS）为8.0个月,优于FOLFOX方案的4.4个月,差异有统计学意义（P=0.038）。常见不良反应多为1～2级,主要为白细胞减少、中性粒细胞减少、乏力、恶心、皮疹等。20例接受化疗患者的中位OS为26.9个月,优于10例未接受化疗的4.4个月,差异有统计学意义（P＜0.001）。结论 化疗可延长晚期十二指肠癌患者的生存时间。GEMOX方案和FOLFOX方案均对晚期十二指肠癌一线治疗有效,且耐受性良好,其中GEMOX方案的中位PFS可能更长。     

索拉非尼治疗转移性肾癌的疗效与安全性观察

目的:评估63例转移性肾细胞癌（metastatic renal cell carcinoma,mRCC）患者服用索拉非尼的疗效及安全性。方法:前瞻性观察2010年6月至2018年6月就诊于西安交通大学第一附属医院肿瘤内科及中华慈善总会索拉非尼援助赠药项目mRCC患者共计71例,其中63例可评价疗效及安全性。使用SPSS 18.0 软件进行K-M单因素生存分析,所得阳性因素导入COX回归模型进行多因素分析,明确影响索拉非尼治疗mRCC疗效的因素。结果:63例可评价mRCC患者中,无CR患者,PR 18例,SD 22例,PD 23例,ORR为28.57%（18/63）,DCR为63.49%（40/63）;中位PFS为14月（3~51月）,中位OS为29月（6~69月）;所有不良反应均可控或随剂量减少而降低。索拉非尼作为mRCC一线治疗者39例,二线及以上治疗者24例。一线和二线及以上治疗的ORR及DCR均无统计学差异,且中位PFS分别为24月（4~51月）和13月（3~42月）（P=0.021）。COX回归分析示,索拉菲尼是否为一线治疗是影响PFS的独立危险因素（P=0.030）。结论:索拉非尼治疗mRCC疗效确切,不良反应较少,并且是否为一线治疗是影响患者中位PFS的独立预测因素。     

雷替曲塞联合奥沙利铂二线治疗晚期胃癌的疗效及安全性

目的:观察雷替曲塞联合奥沙利铂二线治疗晚期胃癌的疗效及安全性。方法:选取2010年1月至2015年10月化疗失败后的30 例晚期胃癌患者，随机分成2组（各15例），一组予雷替曲塞联合奥沙利铂治疗（观察组），即雷替曲塞3 mg/m2，d1；奥沙利铂85 mg/m2，d1。另一组予卡培他滨联合奥沙利铂治疗（对照组），即卡培他滨 1 000 mg/m2，bid po，d1~14，奥沙利铂 130 mg/m2，d1。以上两组方案21 d 为1个周期，每2 个周期评价疗效。结果:观察组 vs 对照组疾病控制率（DCR）73.33% vs 66.67%（P=0.69），总有效率（RR）20% vs 13.33%（P=0.62），中位无进展生存时间（mPFS）3.91 个月 vs 3.72个月（P=0.32），中位生存时间（mOS）8.07个月 vs 6.48个月（P=0.64）。恶心、呕吐发生率、白细胞减少、血小板减少、周围神经毒性、口腔黏膜炎、腹泻、转氨酶升高及心脏毒性，两组比较无差异。结论:对于晚期胃癌的二线化疗，雷替曲塞联合奥沙利铂疗效不劣于其他方案，且毒副反应可耐受，可作为晚期胃癌的一种治疗选择。     

βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

Background:Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both βIII- and βV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.Methods:Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of βIII- and βV-tubulin was morphometrically quantified.Results:Median pre-treatment H-score for βIII-tubulin was 110 (range: 0-290), and 160 for βV-tubulin (range: 0-290). Low βIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high βV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high βV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy.Conclusion:Expression of βV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of βIII-tubulin. Prospective evaluation of βIII/βV-tubulin expression in NSCLC is warranted.     

纤维蛋白原预测晚期非小细胞肺癌化疗的疗效及预后

目的:探讨纤维蛋白原在晚期非小细胞肺癌(NSCLC)患者中对预测化疗疗效及预后的临床意义。方法:我们回顾性分析了251例晚期非小细胞肺癌患者化疗前后纤维蛋白原水平与临床病理特征、化疗前后纤维蛋白原水平的变化与化疗疗效、化疗前后纤维蛋白原水平变化与不同化疗方案、化疗前纤维蛋白原与预后的关系。结果:男性患者化疗前纤维蛋白原水平高于女性(P=0.001),ECOG 1分的患者化疗前后纤维蛋白原水平均高于ECOG 0分的患者(P=0.000、P=0.002)。化疗前有高纤维蛋白原血症的153例患者化疗后纤维蛋白原水平显著降低(P=0.004),在这部分人群中,疾病部分缓解（PR）组、疾病稳定(SD)组和疾病进展（PD）组纤维蛋白原水平降低差异有统计学意义（P=0.001、P=0.003、P=0.033）。总体人群化疗前高纤维蛋白原血症患者的纤维蛋白原在PD组明显升高(P=0.016)。不同化疗方案与纤维蛋白原水平变化不相关(P=0.545)。高纤维蛋白原组、低纤维蛋白原组的中位PFS分别为142天和204天,中位OS分别为317天和427天,差异有统计学意义（P＜0.001）。而且两组患者中位PFS及中位OS在DP、TP和GP方案组差异有统计学意义。Cox风险比例模型显示,ECOG 1分及纤维蛋白原升高是影响PFS和OS的独立因素。结论:晚期非小细胞肺癌患者纤维蛋白原的变化与化疗疗效相关,高纤维蛋白原水平是预后不良因素。     

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective:To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after first-line chemotherapy in Chinese population. Methods:Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time (OS), the second end point was disease control rate (DCR) and progression-free survival time (PFS). DCR included complete response (CR) plus partial response (PR) and plus stable disease (SD). The impact of epidermal growth factor receptor (EGFR) mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography (DHPLC). Results:Among 75 enrolled patients, the overall response rate was 37% and the DCR (CR + PR +SD) was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type (25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively). In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS (P=0.029 and 0.017, respectively), however, rash status was the predictor in terms of PFS (P=0.027).Conclusion:Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.     

GP和FP治疗转移性鼻咽癌的疗效观察

目的：观察吉西他滨＋顺铂（GP）方案和氟尿嘧啶＋顺铂（FP）方案治疗晚期复发转移性鼻咽癌的疗效及不良反应。方法：选择放疗后复发转移性鼻咽癌60例,分别采用GP方案或FP方案静脉化疗,21天为1周期。结果：GP组：CR5例、PR19例,有效率（CR＋PR）80％;FP组：CR2例、PR14例,有效率（CR＋PR）53．3％两组有效率有显著差异（P=0．0283）。中位PFS（无进展生存期）GP组8个月,FP组3个月（P=0．0001）。中位OS期（总生存期）GP组11个月,FP组7个月（P=0．0002）。两组毒性均能耐受。结论：GP方案较FP可以更好改善复发转移性鼻咽癌的RR、PFS和OS。     

Clinical Efficacy of Bevacizumab Concomitant with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients withadvanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomlydivided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessedfor disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinicalefficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), diseasecontrol rate (DCR) and rate of adverse responses between two groups were observed and compared. Results:ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group,respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexedgroup were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groupsincluded high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomitingand proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitantwith pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients withadvanced NSCLC.     

贝伐珠单抗联合化疗治疗4例晚期持续/复发性子宫肉瘤

目的：观察贝伐珠单抗（bevacizumab,BEV）联合化疗治疗晚期持续/复发性子宫肉瘤的临床疗效。方法回顾性分析中国医学科学院肿瘤医院院2006年5月至2014年5月接受贝伐珠单抗与化疗联合治疗的4例晚期持续/复发性子宫肉瘤患者的临床资料,评价治疗的总有效率、临床获益率、无进展生存时间（progres-sion free survival,PFS）和总生存时间（overall survival,OS）,并评价治疗的安全性和毒性反应。结果4例患者中,1例达完全缓解,无瘤生存时间为96个月;1例达部分缓解,PFS为13个月,OS为25个月;1例为疾病稳定,PFS为9个月,OS为24个月;1例为疾病进展,PFS为3个月,OS为9个月。治疗总有效率为50％（2/4）,临床获益率为75%（3/4）,平均PFS为30.25个月,平均OS为38.5个月。4例患者发生的与治疗相关的毒副反应主要是骨髓抑制和胃肠道反应,其中有1例患者为4度血液学毒性（血小板减少）,其余3例均为2度骨髓抑制（WBC减少）;非血液学毒性主要是胃肠道反应（恶心、呕吐）,其中2例患者为2度,2例患者为1度。结论BEV联合化疗可有效控制晚期持续/复发性子宫肉瘤,且耐受性良好,可作为治疗晚期持续/复发性子宫肉瘤安全、有效的候选方案。     

FOLFIRI方案二线治疗晚期十二指肠癌的临床观察

目的 探讨FOLFIRI方案二线治疗晚期十二指肠癌的疗效和安全性。方法 回顾分析本院2008年6月至2016年1月接受FOLFIRI方案二线治疗的晚期十二指肠癌患者9例,分别采用RECIST 1.1版与NCI-CTC 4.0版标准评价近期疗效和不良反应。采用Kaplan-Meier法进行生存分析。结果 9例患者均可评价疗效和不良反应,共完成化疗41个周期,中位化疗4个周期（3～8个周期）。9例患者获PR 1例,SD 5例和PD 3例,总有效率和疾病控制率分别为11.1％和66.7％,中位无进展生存期为6.5个月,中位生存期为19.3个月。常见不良反应多为1～2级,主要为白细胞减少、中性粒细胞减少、贫血、乏力、恶心等。结论 FOLFIRI方案对一线治疗失败后的晚期十二指肠癌具有较好的疗效,且耐受性较好。     

Comparison of Efficacy and Toxicity of First Line Chemotherapy with or without Epirubicin for Patients with Advanced Stage Soft Tissue Sarcoma

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin intreating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed acohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and ResearchInstitute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in groupB and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier methodwas used to estimate progress free survival (PFS). Results: According to RECIST criteria , patients in grouptreated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%).Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patientsachieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin basedregimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observedin 13 patients (52%). By Fisher’s exact test, the DCR difference between the two groups was statistically significant(p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic andhematologic toxicities were not statistically significant between the two groups, and the addition of epirobicinwas not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-basedchemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regardingefficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line forpatients with advanced STS.     

存在内科合并症的老年晚期非小细胞肺癌患者一线含铂双药与单药方案化疗的对照研究

目的 探讨含铂双药与第3代化疗药物单药方案化疗在有内科合并症的老年晚期非小细胞肺癌（NSCLC）患者中的疗效和安全性。方法 回顾性分析150例有内科合并症（依据察尔森指数筛选）经细胞学或病理组织学确诊的老年晚期NSCLC患者。按照接受一线化疗方案分为第3代化疗药物单药组（28例）和含铂双药组（122例）,比较两组的疗效及不良反应。结果 所有患者均可评价疗效。单药组获PR 6例（21.4％）,SD 2例（7.1％）,PD 20（71.4％）,有效率为21.4％;双药组获PR 48例（39.3％）,SD 10例（8.2％）,PD64例（52.5％）,有效率为393％,两组有效率差异无统计学意义（P＞0.05）。单药组和双药组的中位无进展时间（PFS）分别为5.0个月和7.0个月（P=0.617）,中位总生存期（OS）分别为7.4个月和10.7个月（P=0.473）。经年龄、ECOG评分和察尔森指数1～2分分层后发现,单药组与双药组的PFS或OS差异均无统计学意义（P＞0.05）;而经察尔森指数3～4分分层后发现,单药组和双药组的中位PFS分别为3.5个月和8.3个月（P=0.001）,中位OS为5.0个月和8.3个月（P=0.019）。不良反应主要包括中性粒细胞减少、贫血、血小板减少和恶心呕吐,单药组不良反应基本为1～2级,双药组3～4级不良反应发生率较单药组高。结论 含铂双药方案一线治疗有内科合并症的老年晚期NSCLC的疗效与第3代化疗药物单药方案类似,而在察尔森指数3～4分患者中前者远期疗效更好,但总体不良反应发生率略高。     

安罗替尼三线以上治疗非小细胞肺癌疗效观察

目的:观察安罗替尼在晚期非小细胞肺癌三线以上治疗中的疗效和不良反应。方法:二线或多线治疗后进展的晚期非小细胞肺癌患者75例（其中55例为二线治疗后,15例为三线治疗后,5例为4线治疗后）。所有患者均给予安罗替尼 12 mg,每天1次口服,连续服用14天,停用1周,每21天重复,直到疾病进展或不能耐受不良反应为止。不能耐受不良反应的患者,根据情况将剂量降至每天10 mg或每天8 mg。每6周复查CT评价疗效。结果:75例患者中,PR 6例,SD 45例,PD 24例,ORR 8.0%,DCR 60.0%,PD 32.0%,PFS和OS分别为5.2个月（95%CI:4.4~6.0）和8.0个月（95%CI:6.1~9.9）。分层结果,45例腺癌中,PR 4例,SD 27例,PD 14例,ORR 8.9%,DCR 68.9%,PD 31.1%。30例鳞状细胞癌中,PR 2例,SD 18例,PD 10例,ORR 6.7%,DCR 66.7%,PD 33.3%。腺癌组与鳞状细胞癌组的DCR比较,P=0.840,无统计学差异,腺癌组与鳞状细胞癌组的PFS分别为4.5个月（95%CI:3.9~5.1）和5.2个月（95%CI:4.2~6.2）,Log-Rank P=0.033,有统计学差异,OS分别为6.7个月（95%CI:3.2~10.2）和8.0个月（95%CI:5.9~10.1）,Log-Rank P=0.057,无统计学差异。不良反应主要是疲劳、食欲减退、手足综合征、头痛和高血压。结论:安罗替尼三线以上治疗非小细胞肺癌有效,鳞状细胞癌患者的PFS显著高于腺癌患者,不良反应可以耐受。     

Docetaxel-carboplatin chemotherapy combined with cetuximab in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC)--results of the nonrandomised phase II study TaxErb

This open label, single arm phase II study was designed to evaluate the efficacy and safety of the addition of cetuximab to first line chemotherapy with carboplatin and weekly docetaxel in patients with advanced non small-cell lung cancer (NSCLC). From February 2007 to December 2008 74 patients with NSCLC (stage IIIB and IV), ECOG PS ≤2 and no prior systemic chemotherapy were enrolled and treated with carboplatin (area under the curve=5 on day 1) and docetaxel (35 mg/m(2) on days 1, 8, and 15). Cycles were repeated every 4 weeks for a minimum of 4 and a maximum of 6 cycles. Cetuximab (400mg/m(2) on day 1 with subsequent doses of 250 mg/m(2) weekly) was administered until progression or intolerable toxicity up to a maximum treatment duration of 12 months. The primary endpoint was the overall response rate (CR+PR) according to RECIST. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Patients received a median of 4 cycles of docetaxel-carboplatin-chemotherapy. The median number of administrations of cetuximab was 14. Sixty-seven patients were evaluable for response. Partial response was seen in 29/67 patients corresponding to an overall response rate (ORR) of 43.3% (95%CI, 28.5-53.7). No patient experienced complete response. The clinical benefit rate (PR+SD) was 79.1%. The 1-year rates for PFS and OS were 11.2% and 64.4%, respectively. Median PFS was 4.8 months (95%CI, 3.70-5.31) and median OS 12.9 months (95%CI 8.26-∞). Adverse events were mainly grades 1-2. Skin toxicity (76% of pts), dyspnea (36.5%) and anemia (31.1%) were most frequent. Results from this phase II study suggest that the addition of cetuximab to first-line doublet carboplatin and weekly docetaxel results in a considerable clinical efficacy with an acceptable toxicity profile for patients with advanced or metastatic NSCLC.