一线序贯应用厄洛替尼与化疗治疗晚期非小细胞肺癌的临床研究

 目的　评价化疗后序贯给予厄洛替尼在一线治疗非小细胞肺癌（NSCLC）中的客观缓解率和不良反应。方法　23例PS 0～1分的ⅢB～Ⅳ期NSCLC患者一线接受GC化疗方案（吉西他滨1250 mg／m2 第1、8天,顺铂75 mg／m2 第1天或卡铂AUC＝5第1天）,并序贯给予厄洛替尼（150 mg,第15天至第28天）,每28 d为1个周期,观察患者的客观疗效及不良反应。结果　23例患者接受95个周期的化疗,所有患者均可评价疗效。完全缓解（CR）0例,部分缓解（PR）7例（30.4 %）,疾病稳定（SD）14例（60.9 %）,疾病进展（PD）2 例（8.7 %）;总体客观缓解（RR）30.4 %,疾病控制（DCR ）91.3 %。Ⅲ度以上不良反应为白细胞减少3例（13.0 %）,皮疹2例（8.7 %）,恶心呕吐、血小板减少各2例（8.7 %）,没有出现治疗相关的间质性肺病。结论　GC化疗方案序贯厄洛替尼治疗模式的近期疗效较好,不良反应在患者可耐受范围内,远期疗效有待进一步观察。     

厄罗替尼一线治疗中晚期非小细胞肺癌老年患者的临床观察

目的:评价厄罗替尼一线治疗中晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)老年患者的疗效和安全性.方法:2007年5月-2008年12月首次确诊的35例70～81岁中晚期NSCLC老年患者,其中鳞状细胞癌18例、腺癌13例、细支气管肺泡癌4例;吸烟者19例,不吸烟者16例.所有患者均接受厄罗替尼150 mg/d口服治疗,直至疾病进展或出现无法耐受的不良反应.对所有患者均进行随访,观察近期疗效和不良反应,并计算生存情况.结果:35例患者中,1例获得完全缓解,16例获得部分缓解,10例疾病稳定,8例疾病进展;总有效率为48.6％ (17/35),疾病控制率为77.1％ (27/35).中位至疾病进展时间为6.4个月,中位总生存期为12.7个月,1年生存率为48.6％ (17/35).性别、病理类型和吸烟史与疾病控制率相关(P＜0.05).不良反应主要为皮疹和腹泻,只有1例患者因较为严重的皮疹和腹泻而减少厄罗替尼剂量.结论:厄罗替尼一线治疗中晚期NSCLC老年患者可取得较好的疾病控制率和临床获益,不良反应可以耐受.     

Efficacy and safety of first-line erlotinib in elderly patients with advanced non-small cell lung cancer

TaRceva LUng cancer Survival Treatment (TRUST) was an open-label, phase IV study of advanced non-small cell lung cancer (NSCLC). Patients failing or unsuitable for chemotherapy or radiotherapy received erlotinib 150 mg/day until progression. We examined a subpopulation of elderly patients (≥70 years) receiving first-line erlotinib (n=485) in TRUST. In this subpopulation, disease control rate (n=356 with best response data available) was 79% (vs. 69% for the overall TRUST population; p<0.0001); median progression-free survival (PFS) was 4.57 months [95% confidence interval (CI), 3.68-5.22]; median overall survival (OS) was 7.29 months (95% CI, 6.27-8.67); and one-year survival, was 36.6%. PFS and OS were significantly longer in patients developing rash, compared to those without, and in those with good performance status (PS; 0/1), compared to poor PS (≥2). Eighty-seven subpopulation patients (18%) had an erlotinib-related AE; other than the protocol-defined frequent adverse events (AEs); 4% had a grade ≥3 erlotinib-related AE, 7% had an erlotinib-related serious AE. In the subpopulation, dose reductions were required in 27%, most (97%) were reductions to 100 mg/day; treatment was discontinued in 10%, and one death was associated with treatment-related toxicity (<1%). Erlotinib was effective and well-tolerated and may be considered for elderly patients with advanced NSCLC who are unsuitable for standard first-line chemotherapy or radiotherapy.     

A cross-market cost comparison of erlotinib versus pemetrexed for first-line maintenance treatment of patients with locally advanced or metastatic non-small-cell lung cancer

Erlotinib and pemetrexed were approved by the European Medicines Agency for first-line maintenance treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) to prolong overall survival after first-line therapy. An adjusted, matched, indirect comparison of erlotinib and pemetrexed suggested that survival benefits were not statistically significantly different between treatments. We conducted a cost-comparison analysis of erlotinib versus pemetrexed in first-line maintenance treatment of locally advanced or metastatic, non-squamous NSCLC in France, Germany, Italy and Spain, performed from the perspective of national health-care decision-makers or purchasers. The analysis was limited to direct costs and comprised drug-acquisition costs, administration costs and costs of treating adverse events (AEs). A one-way sensitivity analysis on administration, acquisition and AE costs was also performed. Total monthly per-patient treatment costs for erlotinib in France, Germany, Italy and Spain were €2140, €2732, €1518 and €2048, respectively, and for pemetrexed €3453, €5534, €2921 and €3164, respectively. AE cost was greater for pemetrexed in all countries, as was administration cost. As an oral treatment, erlotinib is not associated with any administration costs, except in Germany, where the cost is lower than for pemetrexed. The sensitivity analysis showed acquisition costs to be the main driver of total monthly per-patient costs. Erlotinib appears to be a cost-saving treatment alternative to pemetrexed, producing comparable survival benefits, based on an indirect comparison, at a lower cost.     

Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer

BackgroundGiven the growing number of drugs available for non-small-cell lung cancer (NSCLC), an effect of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. We examined the relation between postprogression survival (PPS) and OS in phase III trials of first-line chemotherapy for advanced NSCLC.Patients and methodsA literature search identified 69 trials that were published during the past decade. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the relation between OS and either PFS or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment.ResultsThe average PPS was longer in recent trials than in older trials (6.5 versus 4.4 months, P < 0.0001). For all trials, PPS was strongly associated with OS (r = 0.82), whereas PFS was moderately associated with OS (r = 0.43). The correlation between OS and PPS in recent trials was stronger than that in older trials (r = 0.89 and 0.66).ConclusionsOur findings indicate that, especially for recent trials, PPS is highly associated with OS in first-line chemotherapy for advanced NSCLC, whereas PFS is only moderately associated with OS.     

Safety profiles of erlotinib therapy in patients with advanced non-small-cell lung cancer

Erlotinib is an orally available, small-molecule EGF receptor tyrosine kinase inhibitor. It has shown promising activity in chemotherapy-relapsed patients with advanced non-small-cell lung cancer and is now approved in many countries. To date, there have been a number of clinical studies of erlotinib therapy demonstrating its safety as well as its efficacy. This article summarizes clinical study results in advanced non-small-cell lung cancer, so that we can comprehensively understand the toxicities expected with erlotinib in non-small-cell lung cancer patients.     

老年晚期非小细胞肺癌一线治疗

非小细胞肺癌(non-small-cell lung cancer,NSCLC)是发病率和死亡率很高的恶性肿瘤之一。随着肿瘤精准治疗快速发展,针对NSCLC的治疗手段也层出不穷。老年患者在NSCLC患者中所占比例最高,如何针对老年患者群体制定合理治疗方案非常重要。本文结合NSCLC治疗传统手段与最新进展,从驱动基因阳性和驱动基因阴性两个方面展开讨论,总结老年晚期NSCLC一线治疗的基本策略,以期为临床治疗提供参考。     

盐酸埃克替尼治疗老年晚期非小细胞肺癌患者的临床观察

目的 观察盐酸埃克替尼治疗老年晚期非小细胞肺癌的近期疗效及安全性.方法 回顾性分析老年晚期非小细胞肺癌患者24例,均口服单药盐酸埃克替尼,每次125 mg,每日3次,直至病情进展或出现无法耐受的不良反应.观察近期疗效及不良反应.结果 全组24例患者中无完全缓解患者,部分缓解6例,病情稳定11例,病情进展7例,客观缓解率25.0％ (6/24),疾病控制率70.8％ (17/24);24例患者中有14例(58.3％)口服盐酸埃克替尼后有不同程度的症状缓解,咳嗽、胸闷、气喘症状改善最为明显.安全性方面,皮疹发生率20.8％,腹泻发生率12.5％,为Ⅰ～Ⅱ级不良反应;无患者因无法耐受药物不良反应而停药.结论 盐酸埃克替尼单药治疗老年晚期非小细胞肺癌有较好的近期疗效,安全性好,值得临床进一步研究.     

厄罗替尼治疗晚期非小细胞肺癌19例临床疗效

目的评价厄罗替尼治疗ⅢB～Ⅳ期非小细胞肺癌（NSCLC）的疗效和患者不良反应。方法19例患者均为经病理证实的、至少接受过一种方案全身化疗的晚期NSCLC患者。厄罗替尼150mg／次,1次／d,口服,直至病情进展或出现不能耐受的不良反应。采用实体瘤疗效评价标准（RECIST）评价疗效,美国国立癌症研究所毒性评价标准（CTCAE）评价不良反应。结果19例患者客观缓解率（ORR）为21．1％（4／19）。疾病控制率（完全缓解＋部分缓解＋稳定）为84．2％（16／19）,疾病无进展生存时间（PFS）3～36个月,中位PFS7．5个月;生存时间9～39个月,中位生存时间15．9个月。不良反应主要是皮疹16例（84．2％）,腹泻11例（57．9％）,多为Ⅰ～Ⅱ度;Ⅲ度丙氨酸氨基转移酶升高1例;未出现Ⅳ度药物相关不良反应。结论厄罗替尼对既往化疗失败的局部晚期或转移性NSCLC患者有较好的疗效和安全性。     

Gefitinib as first-line, compassionate use therapy in patients with advanced non-small-cell lung cancer

PURPOSE: To evaluate the efficacy of single-agent gefitinib (Iressa, ZD1839), an oral, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, as first-line compassionate use therapy for advanced non-small-cell Lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients who were unfit or refused chemotherapy received oral gefitinib 250mg daily as first-line therapy for the treatment of recurrent or metastatic NSCLC in a compassionate use program at a single institution. RESULTS: Four of 22 evaluable patients (18%), two with adenocarcinomas and two with bronchioloalveolar carcinomas, had an objective response and five patients (23%) had stable disease. Duration of response or stable disease was 3.5-22+ months. Median time to progression was 2.2 months, median survival was 12.6 months and 1-year survival 52%. The partial response plus stable disease rate by Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 4/5 for PS 0 patients; 3/6 for PS 1-2 patients; and 2/14 for PS 3-4 patients. The two patients with PS > 2 who derived benefit from gefitinib had PS 3 due to co-morbidities. Two patients discontinued therapy due to severe toxicities: one patient had severe liver dysfunction and hemorrhagic cystitis, and another patient developed diarrhea with hypotension. A correlation between rash and antitumor activity was noted. Of seven patients who received chemotherapy subsequent to gefitinib, one had a partial response, three had stable disease, two progressed, and one was non-evaluable for response. CONCLUSION: We report encouraging response and survival results with gefitinib as first-line treatment in unselected patients with advanced NSCLC. Gefitinib monotherapy should undergo further evaluation as first-line therapy in advanced NSCLC.     

Clinical retrospective analysis of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer

In order to evaluate the clinical efficacy and the safety profile of molecularly targeted therapies as a palliative approach in elderly populations affected by advanced thoracic neoplasms, we retrospectively studied, in terms of effectiveness and toxicities, a group of pretreated elderly metastatic non-small cell lung cancer (NSCLC) patients admitted to our institution and treated with erlotinib at standard daily/dose. Forty-three patients aged 70 years or older who had previously failed on chemotherapy or radiotherapy were treated with oral Eerlotinib (150 mg/d) until disease progression or unacceptable toxicity. Clinical data, pathological types, potential prognostic factors, efficacy and toxicity of erlotinib were included in this analysis. In our series we observed: objective responses in six patients (14%) and stable disease in 15 (35%). Skin rash was the most common side effect (67%). Grade 3–4 adverse events were observed in 16 cases (37%). The median overall survival and the median progression-free survival were 8.4 months (CI 95%: 0.7–43.6) and 3 months (CI 95%: 0.4–28.4), respectively. Patients with adenocarcinoma achieved the best disease control rate (p = 0.027), while not/former smokers showed a better response (p = 0.069). In our experience the use of erlotinib after chemotherapy failure in an unselected elderly population affected by NSCLC showed moderate efficacy and a moderate safety profile. However, erlotinib represents a valid option in this setting, but other factors such as biological information, comorbidities and concomitant medications need to be carefully take into consideration in this particular subset of cancer patients.     

Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy

BackgroundThe EML4-ALK fusion oncogene represents a recently identified molecular target in a subset of patients with non-small-cell lung cancer (NSCLC). Limited data have been available, however, on the outcome of first-line platinum-based chemotherapy in patients with EML4-ALK-positive advanced NSCLC who have not been treated with an ALK kinase inhibitor.Patients and methodsThe efficacy of platinum-based chemotherapy was compared between patients with advanced nonsquamous NSCLC who harbor EML4-ALK and those who harbor EGFR mutations and those with neither molecular abnormality.ResultsAmong 200 patients with advanced nonsquamous NSCLC, 18 (9.0%) were positive for EML4-ALK, 31 (15.5%) harbored EGFR mutations, and 151 (75.5%) were wild type for both abnormalities. Platinum-based combination chemotherapy showed similar efficacies in the EML4-ALK, EGFR mutation, and wild-type cohorts in terms of response rate and progression-free survival, and overall survival in the EML4-ALK cohort closely resembled that in the wild-type cohort. Within the EML4-ALK cohort, patients with variants 1 or 3 of the fusion gene were predominant and did not appear to differ in their sensitivity to the platinum-based regimens.ConclusionPatients with EML4-ALK-positive advanced NSCLC manifest an aggressive clinical course similar to that of those with wild-type tumors if the effective targeted therapy is not instituted.     

老年人晚期非小细胞肺癌化疗疗效及预后分析

目的探讨年龄≥65岁的晚期非小细胞肺癌（NSCLC）患者含铂方案化疗疗效及预后因素。方法回顾性分析70例年龄≥65岁的ⅢA～Ⅳ期NSCLC患者一线含铂方案化疗疗效及不良反应;Kaplan—Meier法分析生存情况,COX回归法进行多因素预后分析。结果全组中位化疗数为3个周期,共有53例患者可评价疗效,总有效率41．5％（22／53）,且疗效不受年龄影响（X^2=1．945,P=0．378）;中位无进展生存时间6．0个月,中位生存时间12．5个月;化疗相关血液毒性发生率高;多因素分析提示ECOG评分、远处器官转移数目、化疗周期数是影响预后的独立因素。结论老年晚期NSCLC患者一线含铂方案化疗具有较高疗效,但不良反应发生率高,化疗耐受性较差,合理选择患者是关键;ECOG评分差、多发远处器官转移患者难以从化疗中获益;而对于可耐受化疗患者,3—6周期化疗可明显改善预后。     

艾迪联合化疗治疗老年晚期NSCLC的临床观察

目的 观察艾迪注射液联合以铂类为基础的联合方案化疗治疗老年性晚期非小细胞肺癌(NSCLC)的近期疗效、生活质量和毒副反应.方法 将96例60岁以上经细胞学或病理学证实的晚期NSCLC患者随机分为两组,治疗组用艾迪联合化疗,对照组单用化疗.每例患者至少治疗2个周期以上进行疗效评价.结果 两组近期疗效差异无统计学意义(P＞0.05).治疗组生活质量Kamofsky评分提高率60.0%,对照组提高率35.0%,两组差异有统计学意义(P＜0.05).治疗组白细胞减少和肝肾毒性的发生率显著少于对照组(P＜0.05).结论 艾迪注射液联合化疗具有改善生活质量和减毒作用,增加患者化疗耐受性.     

替吉奥单药三线或多线治疗老年晚期非小细胞肺癌的临床观察

目的：观察替吉奥单药三线或多线治疗老年晚期非小细胞肺癌的有效性及安全性。方法回顾性分析40例老年晚期非小细胞肺癌患者,服用替吉奥单药80 mg/（m2· d）,每天早晚分服,连用21 d,休息7 d,1个周期为28 d,每两个周期对不良反应以及近期疗效进行评估。结果对40例患者进行评估,在评价的过程中出现完全缓解（CR）、部分缓解（PR）、病情稳定（SD）以及疾病进展（PD）的患者数分别为0例、3例（7.5%）、22例（55%）、15例（37.5%）,客观缓解率（ORR）为7.5%（3/40）,疾病控制率（DCR）为62.5%（25/40）,中位无进展生存期为3.6个月（95%CI 2.1~4.9）,治疗后30%的患者体力状态有所改善,最常见的不良反应为恶心呕吐29例（72.5%）、厌食28例（70%）、乏力28例（70%）、白细胞减少18例（45%）、血小板减少11例（27.5%）、贫血9例（22.5%）,且仅有2例为3级白细胞减少,其他均为1～2级骨髓抑制;未观察到药物相关严重不良反应或死亡。结论替吉奥单药治疗老年晚期非小细胞肺癌疗效较好,同时无严重的不良反应,部分患者的生活质量会得到有效改善,是晚期非小细胞肺癌的三线或三线以上治疗的有效方法。     

异长春花碱单药化疗高龄晚期非小细胞肺癌

目的：评价高龄NSCLC患者用异长春花碱单药化疗的生存率,生活质量及能否耐受。方法：治疗高龄晚期非小细胞肺癌40例,治疗组20例予以持续深静脉输注异长春花碱（NVB）24小时7．5mg/m^2第1－5天,同时第一天快速静滴异长春花碱7．5mg/m^2,三周后重复;对照组20例运用中药薏芯仁提取物200ml/天静滴20天1疗程辅以其他支持治疗,每1月为1疗程,所有病例至少完成两个疗程,除非治疗中发现病情进展,结果：治疗组有效率35％（7／20）,患者中位生存期 7．2个月,一年生存率25％,对照组有效率10％（2／20）,患者中位生存期4．8个月,一年生存率5％,结论：对高龄晚期非小细胞癌患者,异长春花碱单药治疗较中药薏芯仁为主的支持治疗有更好的疗效,生活质量,更长的生存期,且毒副反应轻微,可以耐受。     

一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

Objective To evaluate RR,DCR,PFS,OS and toxicities in a population affected by NSCLC using gefitinib as maintenance therapy after the first line chemotherapy.Methods From January,2006 to January,2008,seventy-one patients were enrolled with stable disease or partial response after firstline chemotherapy.They were divided into the observing group and the control group.Gefitinib was administered at the dose of 250 mg in observing group;placebo was also administered everyday in control group.Results Of 71 assessable patients ,overall response rate was 36.1% (13/36) in observing group and 14.3 % (5/35) in control group respectively (x 2 = 4.633,P = 0.036),and one patient (2.8 %) was observed complete response (CR) in observing group.The disease control rate was 83.3 % (30/36) in observing group and 42.9 % (15/35) in control group,respectively,(x2 = 14.782,P ＜ 0.001).The median PFS (progression free survival time) was 13 weeks in observing group and 11 weeks in control group respectively (x2 = 10.401,P =0.001).The median overall survival time (OS) was 13.2 months in observing group and 10.4 months in control group respectively (x2 = 7.696,P= 0.006).The median OS was 18.5 months in women and 11.2 months in men(x2 =22.864,P=0.011) .The median OS was 15.3 months in non-smokers and 10.3 months in smokers (x2 =10.389,P =0.007).The median OS was 16.0 months in adenocarcinoma and alveolar cell carcinoma patients and 10.2 months in squamous cell carcinoma patients (x 2 = 4.638,P = 0.001).The most common toxicity was rash ,diarrhea,fatigue and dry skin itching,and most of them were 1 or 2 grade.Conclusion Maintenance therapy with gefitinib after first-line chemotherapy may improve overall survival time and progression free survival time in patients with NSCLC,and it is effective and safe.