厄洛替尼在老年非小细胞肺癌脑转移治疗中的临床应用

目的探讨厄洛替尼(TKI)在老年非小细胞肺癌(NSCLC)脑转移治疗中的临床疗效与毒副作用。方法 32例临床确诊的老年非小细胞肺癌脑转移患者,应用厄洛替尼150 mg/d,直到病情进展。观察近期临床疗效和毒副作用。结果厄洛替尼治疗非小细胞肺癌脑转移完全缓解(CR)3例,部分缓解(PR)10例,稳定(SD)10例,进展(PD)9例,中位总生存率(OS)为10.3个月,临床缓解率90.6%,临床受益率(CR+PR+SD)71.9%,1年生存率为35.9%,2年生存率为18.6%,性别、病理类型和吸烟史与临床受益率有一定关联。厄洛替尼毒副作用主要是皮疹、腹泻、座疮、皮肤干燥等。结论上皮生长因子细胞增殖和信号传导受体(EGFR)突变、腺癌、女性、不吸烟的老年肺癌患者选用厄罗替尼临床获益较多,野生型和未检测突变的老年肺癌患者选用厄罗替尼也可部分受益,具有较好的临床疗效,毒副反应轻,可耐受。     

厄洛替尼治疗晚期非小细胞肺癌的疗效及安全性研究

目的厄洛替尼是治疗非小细胞肺癌的靶向药物,多项国内外研究已证明该药可延长非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的生存。本研究回顾性总结了厄洛替尼在非选择NSCLC人群中的应用,旨在探讨厄洛替尼治疗晚期非小细胞肺癌的远期疗效及安全性。方法回顾分析本院2006年3月至2009年7月之间接受化疗后应用厄洛替尼治疗化疗失败的晚期NSCLC患者,口服150 mg/d厄洛替尼直至疾病进展,观察疗效、生存时间和副反应。结果共有36例患者入组。36例患者中PR 22.2%(8/36),SD 50.0%(18/36),PD 27.8%(10/36),CR=O,DCR(CR+PR+SD)72.2%;PFS为5.8个月。其中腺癌与非腺癌、无吸烟者与吸烟者的疗效差异无统计学意义,但是生存曲线提示腺癌比非腺癌患者(7.6个月vs 1.0个月,P=0.037)、无吸烟比吸烟患者(11.1个月vs 4.6个月,P=0.025)具有更长的PFS,差异有统计学意义;性别因素未能影响疗效或PFS。毒副作用主要为为轻度皮疹、腹泻、转氨酶升高。结论厄洛替尼治疗晚期非小细胞肺癌有效,对腺癌和非吸烟人群有一定优势,且耐受性良好,是治疗晚期非小细胞肺癌患者的一个新的选择。     

厄洛替尼单药一线治疗老年晚期非小细胞肺癌32例临床观察

目的探讨厄洛替尼单药一线治疗老年晚期非小细胞肺癌临床疗效及毒副反应,为老年患者治疗提供新的方向。方法收集本院肿瘤内科经组织学或细胞学证实的老年晚期非小细胞肺癌并自愿接受单药厄洛替尼治疗的患者32例,观察近期疗效及毒副反应,并通过随访观察无进展生存期(PFS)、总生存期(OS)。结果完全缓解为0,部分缓解为43.8%,疾病稳定为34.4%,疾病进展为21.9%。有效率为43.8%。PFS为4.28个月,OS为10.55个月。鳞癌患者的PFS和OS明显低于腺癌患者(P<0.01),吸烟患者的PFS和OS明显低于不吸烟的患者(P<0.01)。主要毒副反应为皮疹,腹泻,厌食,乏力,且以Ⅰ、Ⅱ度为主。结论厄洛替尼单药一线治疗老年晚期非小细胞肺癌安全有效。     

厄洛替尼联合放疗治疗非小细胞肺癌脑转移效果的临床分析

肺癌是最常见的恶性肿瘤之一,非小细胞肺癌约占80%左右,其中30%在疾病不同阶段发生脑转移。一旦发生脑转移,预后极差。脑转移瘤治疗方法主要有全脑放疗、立体定向放射、外科手术和化疗,厄洛替尼可适用于两个或两个以上化疗方案失败的局部晚期或转移的非小细胞肺癌的三线治疗。为此,作者分析了近年来应用厄洛替尼联合全脑放疗治疗的30例非小细胞肺癌脑转移患者的临床资料,以观察其联合治疗的效果。     

厄洛替尼单药一线治疗非小细胞肺癌的研究进展

高效低毒的分子靶向治疗药物厄洛替尼,在非小细胞肺癌(NSCLC)的二、三线治疗以及序贯和维持治疗中,已经显示出其能够使患者临床获益.厄洛替尼单药为晚期NSCLC的一线治疗新的选择方案.本文就其在老年、体力状态较差、不吸烟以及存在表皮生长因子(EGFR)敏感性突变或K-ras耐药突变的NSCLC患者中的应用作一综述.     

吉非替尼与厄洛替尼治疗非小细胞肺癌临床疗效比较及药物经济学评价

目的比较吉非替尼与厄洛替尼治疗非小细胞肺癌的临床疗效和药物经济学评价。方法比较实验组(服用吉非替尼)38例和对照组(服用厄洛替尼)34例NSCLC患者分别给予吉非替尼和厄洛替尼治疗的临床疗效、不良反应发生情况及药物经济学评价结果。结果两组患者有效率及临床控制率比较,差异无统计学意义(P0.05);两组肿瘤进展时间及1年生存率比较,差异无统计学意义(P0.05);两组患者不良反应发生率及严重程度比较,差异无统计学意义(P0.05);实验组患者治疗费用及费用疗效比均显著低于对照组,差异具有统计学意义(P0.05)。结论吉非替尼与厄洛替尼治疗NSCLC疗效相当,但吉非替尼更加经济适用。     

化疗间期序贯应用厄洛替尼治疗晚期非小细胞肺癌的疗效观察

目的：观察化疗间期序贯应用厄洛替尼治疗晚期非小细胞肺癌（NSCLC）的疗效。方法42例NSCLC患者,27例为初治患者,应用GC方案实施化疗;15例为复治患者,应用培美曲塞或者多西他赛进行治疗。患者的化疗间歇期序贯,给予150 mg/d厄洛替尼,持续15~28 d。治疗的1个周期为28 d,连续治疗6周,直至患者疾病产生新进展或者不能忍受产生的不良反应。结果42例晚期非小细胞癌患者的治疗过程中,在化疗间期序贯应用厄洛替尼,治疗总有效率为21.43%,疾病控制率为83.33%,具有较好疗效。结论在NSCLC患者的化疗间期序贯应用厄洛替尼具有较好疗效,患者可耐受产生的不良反应,需进一步观察远期疗效。     

1例盐酸厄洛替尼致不良反应的药学监护

盐酸厄洛替尼是一种口服高效表皮生长因子受体酪氨酸激酶（EGFR）选择性抑制药,通过影响细胞内磷酸化过程来抑制信号通路的传导,进而抑制肿瘤细胞的扩散及增殖来达到抗肿瘤的目[2]。大型临床研究证实,厄洛替尼靶向治疗非小细胞肺癌（NSCLC）晚期,能显著延长患者的生存期。而对于老年及身体状态评价差的患者,厄洛替尼单药不失为一线治疗的新选择[3]。本文讨论了1例NSCLC晚期患者单药使用盐酸厄洛替尼靶向治疗过程中出现严重药物疹及其他不良反应的药学监护。     

化疗药物联合精确放疗治疗多发脑转移研究进展

随着铂类药物及20世纪90年代后多种靶向药物的问世,使得非小细胞肺癌等常见肿瘤的化疗疗效得到提高[1]。有研究表明厄洛替尼及吉非替尼联合全脑放疗治疗非小细胞肺癌脑转移具有较好疗效、不良反应轻、可耐受、生存期延长越来越广泛地应用于临床[2,3]。尽管脑转移后血脑屏障的完整性部     

康莱特注射液联合厄洛替尼治疗晚期非小细胞肺癌的观察

目的 观察康莱特注射液联合厄洛替尼治疗晚期非小细胞肺癌(NSCLC)的临床疗效和不良反应.方法 非小细胞肺癌(NSCLC)患者63例,随机分为治疗组32例和对照组31例,治疗组应用康莱特注射液联合厄洛替尼治疗,对照组采用厄洛替尼治疗,比较2组的客观疗效、生活质量及不良反应.结果 治疗组总有效率40.6%、疾病控制率75.0%,均优于对照组的32.2%和61.3%(P＜0.05);生活质量上,Karnofsky评分提高及稳定,治疗组21例占71.9%;对照组18例占58.1%,2组相比较差异有统计学意义(P＜0.05).2组的不良反应比较,皮疹、腹泻、肝功能异常及恶心呕吐差异无统计学意义(P＞0.05).结论 康莱特注射液联合厄洛替尼治疗晚期NSCLC,疗效肯定、改善患者生活质量、不良反应小.     

Phase II study of S-1 monotherapy as a first-line treatment for elderly patients with advanced nonsmall-cell lung cancer: the Central Japan Lung Study Group trial 0404

Although S-1 has been shown to have activity against advanced nonsmall-cell lung cancer (NSCLC), its efficacy for elderly patients remains unclear. This phase II study evaluated the efficacy and safety of S-1 as a first-line treatment for elderly patients. Chemotherapy-na?ve patients aged 70 years or older with stages IIIB to IV or postoperative NSCLC and performance status 1 or lower were eligible. Patients received S-1 approximately equivalent to 80 mg/m/day for 2 weeks followed by a 1-week rest period every 3 weeks. The primary end point was the response rate. Secondary end points were toxicity, disease control rate, progression-free survival, and overall survival. Twenty-nine patients were eligible. The median age was 78 years (range, 70-85 years). The overall response rate and the disease control rate were 27.6 [95% confidence interval (CI), 11.3-43.9%] and 65.5% (95% CI: 48.2-82.8%), respectively. The median progression-free survival time was 4.0 months (95% CI: 4.0-9.8 months). The median overall survival was 12.1 months (95% CI: 13.8-25.5 months) and the 1-year survival rate was 53.6%. No grade 4 toxicities were observed. The only hematological toxicity of grade 3 was anemia in 6.9% of patients. The grade 3 nonhematological toxicities included hyponatremia, anorexia, nausea, oral mucositis, and diarrhea in 3.4% of patients and infection in 6.9% of patients. S-1 monotherapy was effective and well tolerated as a first-line treatment for elderly patients with advanced NSCLC. The results of this study warrant further investigations of this regimen, including a randomized controlled trial.     

Oral tyrosine kinase inhibitors in the first-line treatment of advanced non-small cell lung cancer

INTRODUCTION: In EGFR mutated advanced NSCLC, tyrosine kinase inhibitors are new valid options as first-line treatment. Gefitinib appears a valid alternative to chemotherapy as first-line therapy, in EGFR mutated elderly or unfit patients too, while erlotinib remains an option for subsequent lines of treatment. AREAS COVERED: Areas covered in this review include two international trials, which evaluated erlotinib in chemo-naive EGFR mutated patients both in an Asian and caucasian population, showing a dramatic advantage in terms of progression-free survival and overall response rate as well as gefitinib. Results showed a good safety profile, with side effects of mild to moderate intensity, usually manageable with temporary interruption of treatment. EXPERT OPINION: Investigating EGFR mutations is critical in order to obtain sufficient data. It has now become mandatory for molecular characterization, as part of baseline diagnostic procedures. This approach is also becoming increasingly important during progression of the disease as a sort of 'molecular follow up'. It plays a central role in the right choice of treatment, in an aim to give the best drug to the right patients, overcoming other well known prognostic factors.     

吉非替尼单药一线治疗晚期非小细胞肺癌临床研究

目的评价吉非替尼单药一线治疗在未经化疗的Ⅳ期非小细胞肺癌(NSCLC)患者中的有效性和耐受性。方法23例经组织学或细胞学确诊的未经化疗的Ⅳ期NSCLC患者,予以吉非替尼单药250mg/d口服,直到疾病进展或因严重不良反应不能耐受治疗。2月后评价疗效与不良反应,并随访1年生存率。结果客观有效率为26%,疾病控制率为61%;不良反应轻微,主要是皮疹、乏力、腹泻和肝功能异常。无间质性肺疾病(ILD)发生。1年生存率为58%。结论研究证实了吉非替尼单药一线治疗晚期NSCLC有效并具有良好的耐受性。     

培美曲塞二线或二线以上治疗老年非小细胞肺癌的临床观察

目的：观察培美曲塞二线或二线以上治疗老年非小细胞肺癌的疗效及不良反应。方法回顾性分析一线及二线治疗失败的老年非小细胞肺癌21例,应用培美曲塞单药或联合顺铂或卡铂化疗,化疗1个周期后即评价不良反应;化疗2个周期后行疗效评价。结果21例患者中20例可评价疗效,完全缓解（CR）0例,部分缓解（PR）1例,稳定（SD）12例,进展（PD）7例。客观缓解率（ORR）为5%,疾病控制率（DCR）为65%。中位无进展生存期（PFS）为3.5个月。培美曲塞血液学及非血液学副反应均较轻,主要表现为白细胞减少、血小板减少及肝功能异常,经对症及支持处理后能恢复。培美曲塞联合铂类化疗副反应略重。结论老年非小细胞肺癌患者二线或二线以上应用培美曲塞化疗有一定价值,并且副反应轻,老年患者能耐受。     

Role of erlotinib in the treatment of non-small cell lung cancer: clinical outcomes in wild-type epidermal growth factor receptor patients

Erlotinib is an orally administered small molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Erlotinib at the standard oral daily dose of 150 mg is approved for the treatment of unselected chemorefractory advanced non-small cell lung cancer patients as well as maintenance therapy after first-line chemotherapy. The European Medicines Agency has recently also approved erlotinib as the first-line therapy in patients with EGFR mutations. Although recent studies have identified higher response rates and improved survival with erlotinib in a subset of patients with EGFR mutations, the survival benefit from single agent erlotinib in chemorefractory patients and in the maintenance setting is well observed in EGFR wild-type patients. The role of single agent erlotinib in the first-line setting in special subsets of EGFR wild-type patients (elderly, poor performance status, non-smokers) needs to be further determined. The combination of erlotinib with other targeted therapies has shown promising results and warrants further studies in EGFR wild-type patients.     

Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy: a NICE single technology appraisal

The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinum-containing therapy. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. The ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE. The analysis of the submitted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. Analysis also included reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results. Clinical evidence was derived from a multi-centre, double-blind, randomized, phase III study designed to address the overall population of NSCLC patients. Outcomes included progression-free survival (PFS) and overall survival (OS). The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a first-line therapy, which is now accepted clinical practice in the UK. The evidence considered in this article includes only the population for whom marketing authorizations has been received--that is, patients with stable disease following first-line therapy. The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo. However, no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup. The economic evidence was focussed on the ERG's assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous populations and erlotinib with pemetrexed in the non-squamous population. The incremental cost-effectiveness ratios (ICERs) reported by the manufacturer were ￡39,936 per QALY gained (stable disease, all); ￡35,491 per QALY gained (stable disease, squamous); and ￡40,020 per QALY gained (stable disease, non-squamous). In comparison with pemetrexed, in the cases where erlotinib was considered to be superior or equivalent, erlotinib dominated. In the cases where erlotinib was considered to be slightly inferior, then the ICERs ranged between ￡91,789 and ￡511,351 per QALY gained; these ICERs appear in the south-west corner of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than pemetrexed. The ERG recalculated the base-case cost-effectiveness results in the manufacturer's submission, considering nine key areas where corrections and/or adjustments were required, related to time horizon, discounting logic, costs of erlotinib and pemetrexed, cost of second-line chemotherapy, unit costs, utility values, PFS and OS. This resulted in ERG-revised ICERs for the stable disease squamous population of ￡44,812 per QALY gained, in the stable disease non-squamous population of ￡68,120 per QALY gained, and, when erlotinib was compared with pemetrexed, the result was ￡84,029 per QALY gained. All values were above NICE's perceived willingness-to-pay threshold. After the second Appraisal Committee meeting, the Committee did not recommend the use of erlotinib in this patient population.     

Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation

With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250?mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.     

全脑放疗联合靶向治疗与同步放、化疗治疗非小细胞肺癌脑转移的临床疗效

目的 对比分析全脑放疗联合靶向治疗与同步放、化疗治疗非小细胞肺癌(NSCLC)脑转移的临床疗效及安全性.方法选取NSCLC脑转移病人56例作为研究的对象,经随机数字表法将之分为联合组与放化疗组,联合组病人采取全脑放疗联合靶向药物治疗,放化疗组采取全脑放疗以及同步化疗治疗.对病人进行为期2年的随访,比较两组病人治疗6个月后的临床疗效,并观察病人治疗期间并发症的发生情况以及随访期间的生存情况.结果联合组的脑转移病灶、总体评价的治疗有效率(RR)、疾病控制率(DCR)均显著高于放化疗组(P<0.05);联合组骨髓抑制、消化道反应的发生率均显著低于放化疗组,而皮疹脱屑的发病率则高于放化疗组(P<0.05);联合组1年生存率显著高于放化疗组,且平均生存时间较放化疗组更长(P<0.05);治疗结束后,联合组生存质量上升者显著多于放化疗组,而生存质量下降者则显著少于放化疗组(P<0.05).结论全脑放疗联合靶向治疗应用于NSCLC脑转移病人具有较好的疗效,能够减少不良反应,延长病人的生存时间.     

吉非替尼治疗老年非小细胞肺癌化疗后脑转移的效果分析

目的 研究探讨吉非替尼治疗老年非小细胞肺癌化疗后脑转移的效果及安全性.方法 选择本院2009年6月至2012年6月收治的年龄≥60岁的非小细胞肺癌伴脑转移患者42例,均应用吉非替尼治疗,观察颅内外病灶的近期疗效及远期疗效(疾病进展时间TTP曲线及总生存时间OS曲线),并分析不同临床病理参数下中位TTP和中位OS,以评价吉非替尼治疗的控制效果.结果 42例患者颅内病灶RR率为33.3％,DCR率为97.6％;颅外病灶RR率为31.0％,DCR率为92.9％.42例患者中,有4例患者未进展,38例进展,平均中位TTP为245 d;截止到随访终止日或死亡日期,4例存活,38例死亡,平均中位OS为590 d,1年内生存率为76.2％(32/42),2年内生存率为11.9％(5/42).经统计,不同年龄段、性别、吸烟史、发生脑转移的时间、脑转移灶数目、吉非替尼治疗时机、放疗时间方面,均为影响TTP和OS的独立危险因素.结论 吉非替尼治疗老年非小细胞肺癌化疗后脑转移的效果值得肯定,安全性较好,其中以单发脑转移、一线治疗时机、同步放疗等患者应用吉非替尼治疗控制效果更好.