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。     

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。     

化疗期间序贯应用厄洛替尼治疗晚期非小细胞肺癌的临床疗效观察

目的 观察化疗期间序贯给予厄洛替尼对晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 58例NSCLC晚期患者化疗期间序贯给予厄洛替尼150 mg/ d,给药至疾病进展或不良反应无法耐受.采用实体瘤的疗效评价标准评价疗效.结果 58例患者中客观有效率为27.6%(16/58),疾病控制率为80.0%(47/58).主要的不良反应有皮疹、腹泻和血液系统毒性.主要的不良反应有皮疹、腹泻和血液系统毒性,皮疹多为炎性脓疱疹,常分布于颜面部、颈部、躯干和四肢等.36例出现皮疹,占62.1%.血液系统毒性主要表现为白细胞和血小板减少.结论 化疗期间序贯给予厄洛替尼治疗晚期NSCLC的近期疗效较好,不良反应耐受性好,远期疗效需进一步观察.     

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.     

EGFR-TKIs治疗晚期非小细胞肺癌效果的Meta分析

目的：根据临床研究文献,采用 Meta 分析法综合评价EGFR-TKIs类药物治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效。方法：检索 CNKI、维普、万方、SCI、Pubmed、Science Direct等数据库中2005年至2013 年期间发表的有关EGFR-TKIs对比治疗晚期NSCLC的临床研究资料,采用 RevMan5.0和ITC软件,对入选的国内外10篇有关EGFR-TKIs对比治疗晚期NSCLC的研究文献进行综合定量分析。结果：Meta 分析结果显示,埃克替尼与吉非替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.07(P＝0.69)、1.01(P＝0.89);吉非替尼与厄洛替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.23(P＝0.10)、1.04(P＝0.46);埃克替尼与厄洛替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.32(P＝0.79)、1.05(P＝0.95)。结论：埃克替尼、吉非替尼和厄洛替尼治疗晚期NSCLC的效果无显著性差异,但三者的临床有效性尚需要更多高质量的临床随机对照研究来证实。     

非小细胞肺癌新靶向药物治疗研究进展

非小细胞肺癌(NSCLC)是一种常见的恶性肿瘤,尽管化学治疗适度提高了晚期NSCLC病人的生存率,但总体来说预后仍不乐观。而分子靶向药物治疗具有符合生理、低毒和理论上高效的特点,已越来越成为晚期NSCLC治疗的热点。以肿瘤血管生成为靶点的血管内皮生长因子拮抗药贝伐单抗和抗肿瘤血管生成靶向药物血管内皮抑素显示出明显生存优势;以表皮生长因子受体为靶点的酪氨酸激酶抑制药吉非替尼、厄洛替尼和多激酶抑制药索拉非尼,不良反应少、易耐受、疗效高,显示出较好的应用前景。     

厄洛替尼挽救治疗吉非替尼治疗失败的晚期非小细胞肺癌的疗效

目的评价厄洛替尼作为挽救方案治疗吉非替尼治疗失败的晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法回顾性分析我院收治的96例采用厄洛替尼挽救治疗吉非替尼治疗后进展或复发的NSCLC患者,随访1年,观察有效率(RR)、疾病控制率(DCR)、疾病无进展生存时间(PFS)及不良反应。结果其中CR0例,PR 10例(10.42%),SD 50例(52.08%),PD 36例(37.50%),RR为10.42%,DCR为62.50%。吉非替尼治疗失败后给予化疗,进展后再给予厄洛替尼治疗者PFS为4.4个月;未间隔化疗直接给予厄洛替尼治疗者PFS为3.3个月。SD组以厄洛替尼治疗,RR、PFS分别为23.96%(23/96)、3.2个月,DCR为88.54%(85/96),非SD组DCR为52.08%(50/96),前者DCR显著高于后者(P<0.05)。结论厄洛替尼挽救治疗吉非替尼治疗失败的NSCLC具有较好的临床获益率,尤其是可提高吉非替尼治疗失败的疾病控制率,效果显著,不良反应轻微。     

埃克替尼与厄洛替尼治疗晚期非小细胞肺癌的疗效对比

目的对比埃克替尼与厄洛替尼应用于晚期非小细胞肺癌中的临床疗效。方法 84例晚期非小细胞肺癌患者,随机分为对照组与观察组,各42例。对照组给予患者口服厄洛替尼,观察组给予患者口服埃克替尼,比较两组患者治疗效果与不良反应发生情况。结果两组患者疾病控制率、总缓解率及中位肿瘤进展时间比较差异均无统计学意义(P>0.05);观察组患者的总不良反应发生率为47.6%,显著低于对照组71.4%,差异有统计学意义(P<0.05)。结论埃克替尼与厄洛替尼对晚期非小细胞肺癌有相似疗效,相对于厄洛替尼而言,埃克替尼治疗晚期非小细胞肺癌具有较低的不良反应发生率,具有临床借鉴意义。     

EGFR-TKIs治疗晚期非小细胞肺癌的成本-效果分析

目的：评价埃克替尼、吉非替尼和厄洛替尼三种EGFR-TKIs类药物治疗晚期非小细胞肺癌（NSCLC）的成本-效果。方法：效果数据来源于文献资料的Meta分析结果,成本指直接药品成本,运用传统决策分析的原理和方法,评价三种二线治疗方案的经济性。结果：埃克替尼、吉非替尼和厄洛替尼组的成本分别为143550.85元、200750.00元和260662.14元,有效率分别为27.27%、25.57%和20.66%,疾病控制率分别为74.09%、73.52%和70.56%。结论：埃克替尼作为二线药物治疗晚期NSCLC效果略优于吉非替尼和厄洛替尼,且具有绝对的成本效果优势。     

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.     

厄洛替尼一线治疗老年非小细胞肺癌脑转移7例疗效观察

目的探讨厄洛替尼一线治疗老年非小细胞肺癌(NSCLC)脑转移的疗效与安全性。方法对7例确诊的老年非小细胞肺癌患者,应用厄洛替尼150 mg·d-1,直到病情进展。结果厄洛替尼治疗老年非小细胞肺癌脑转移的ORR为57.1%,DCR为85.7%,中位OS为12月,1年生存率为42.9%,2年生存率为28.6%。结论厄洛替尼一线治疗老年NSCLC脑转移,具有较好的临床疗效,毒副反应轻,可耐受。     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva?; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva trade mark; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan

BACKGROUND: Lung cancer is the most common non-skin cancer and the leading cause of cancer death among men and women in North America. More than half of all patients diagnosed with lung cancer are diagnosed with advanced disease. Most cases of lung cancer are non-small cell lung cancer (NSCLC). Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen. OBJECTIVE: To assess the budgetary impact, from the health plan perspective, of covering erlotinib for treating patients with NSCLC stage IIIb/IV who have failed at least 1 prior chemotherapy regimen. METHODS: An Excel-based model was developed to evaluate costs for U.S. Food and Drug Administration-approved and National Comprehensive Cancer Network guideline-recommended treatment options for second- and third-line NSCLC from the perspective of a U.S. health insurer. In particular, the model compares a formulary with erlotinib and a formulary without erlotinib, including the costs of treatment, drug administration, and adverse effects. The incidence of advanced NSCLC is based on the Surveillance, Epidemiology, and End Results Cancer Registry and adverse effects related to treatment (all agents) in published results of clinical trials. Drug and treatment costs were obtained from publicly available sources in 2005. RESULTS: The base case considers a health plan of 500,000 enrollees. Assuming that erlotinib comprises 30% of second-line treatments and 90% for third-line, total costs of treating stage IIIb/IV NSCLC patients over 1 year are Dollars 382,418 with erlotinib and Dollars 380,968 without erlotinib (difference: Dollars 1,450; 90% confidence interval, -Dollars 61,376 to Dollars 29,855), less than Dollars 0.01 per member per month (PMPM) in 2005. Erlotinib direct cost is offset by reductions in standard chemotherapy-related infusion costs and adverse events. CONCLUSIONS: Based on the analysis, the inclusion of erlotinib on a formulary appears to have a relatively small impact on the annual health care budget or PMPM expenditures if it is used consistent with the product label indications.     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

非小细胞肺癌患者的新选择—厄洛替尼（特罗凯）

目的：综述了厄洛替尼的靶向作用、药动学、临床研究及不良反应皮疹与疗效的关系。方法：通过查阅国内外文献总结了厄洛替尼的单药试验及合并用药试验，并对研究结果进行分析。结果：单药试验表明厄洛替尼能够显著延长患者的生存期并提高生存质量：合并用药试验未发现显著性优势。其不良反应皮疹的发生及程度与患者的生存期及疾病缓解率存在显著性关系。结论：厄洛替尼能够显著延长晚期或转移型非小细胞肺癌患者的生存期，其不良反应皮疹与疗效的相关性仍需进一步研究。