Prolonged survival of gefitinib treatment in patients with advanced and previously treated non-small cell lung cancer

The purpose of this study was to evaluate the survival outcome in patients with advanced and previously treated non-small cell lung cancer given gefitinib (GEF) at our institution. We reviewed the clinical records of 70 Japanese patients,among whom 33 received several chemotherapy treatment modalities including GEF monotherapy (GEF group), and the other 37 were given several chemotherapy treatment modalities without GEF monotherapy (non-GEF group). The median survival time (MST) after second-line chemotherapy in the GEF group was 527 days with 1-year and 2-year survival rates of 59% and 26%, respectively. The MST in the non-GEF group was 175 days with 1-year and 2-year survival rates of 21% and 16%, respectively. Overall survival after second-line chemotherapy in the GEF group was significantly longer than in the non-GEF group (hazard ratio 1.93; 95% confidence interval 1.15-3.53, p=0.014). In our limited clinical experience, chemotherapy treatment including GEF monotherapy appeared to have longer survival than non-GEF treatment.     

EGFR genetic heterogeneity of nonsmall cell lung cancers contributing to acquired gefitinib resistance

Gefitinib is dramatically effective for nonsmall cell lung cancers (NSCLCs) with activating mutations of the epidermal growth factor receptor (EGFR) gene, but these tumors eventually develop drug resistance, attributable to a secondary T790M mutation or acquired MET amplification in some relapsed tumors. We analyzed EGFR mutations in matched pre- and post-therapeutic tumors of 6 gefitinib-responding lung cancers. With conventional PCR-based sequencing, classic mutations were detected in pretreatment samples of each case. The same mutations were readily confirmed in treated lesions of 4 cases, but were absent in those of Cases 1 and 2. Subsequent mutant-enriched peptide-nucleic-acid-mediated PCR clamping and subcloning assays detected the mutation in minor cells of treated lesions of Case 1, but still failed to detect a mutation in Case 2. We thus performed microdissection-based cell cluster mutation analysis of pretreatment tumors, and found that 3, including the first 2, concurrently contained tumor cells with either mutant or wild-type EGFR, although the latter was only a minor fraction. These findings suggest that some NSCLCs are genetically heterogeneous with regard to EGFR mutations; gefitinib-sensitive mutants decrease or vanish while wild clones selectively survive with gefitinib treatment. In addition, T790M was detected in a small fraction of treated lesions of 3 cases, and MET amplification was revealed in 3 treated tumors of Case 2. Thus, our results suggest that multiple mechanisms underlie acquired gefitinib resistance, and selection on a background of EGFR genetic heterogeneity also contributes to acquisition of resistance in a proportion of NSCLCs.     

Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatment

BACKGROUND:

A prognostic model based on clinical parameters for nonsmall cell lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage therapy was devised.

METHODS:

Clinical data regarding a total of 316 metastatic or recurrent NSCLC patients who were treated with gefitinib were analyzed.

RESULTS:

Poor prognostic factors for overall survival (OS) by multivariate analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57‐2.73 [P < .001]), the presence of intra‐abdominal metastasis (HR of 1.76; 95% CI, 1.33‐2.34 [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13‐2.00 [P = .005]), time interval from diagnosis to gefitinib therapy of ≤12 months (HR of 1.48; 95% CI, 1.12‐1.95 [P = .005]), low serum albumin (HR of 1.45; 95% CI, 1.09‐1.92 [P = .009]), progression‐free interval for previous chemotherapy of ≤12 weeks (HR of 1.40; 95% CI, 1.0‐1.84 [P = .015]), white blood cell >10,000/μL (HR of 1.38; 95% CI, 1.02‐1.85 [P = .032]), and ever‐smoker (HR of 1.33; 95% CI, 1.02‐1.75 [P = .033]). Of the 272 patients applicable to this prognostic model, 41 patients (15%) were categorized as a good prognosis group (0‐1 risk factors), 100 patients (37%) as an intermediate prognosis group (2‐3 risk factors), 81 patients (30%) as a poor prognosis group (4‐5 risk factors), and 50 patients (16%) as a very poor prognosis group (≥6 risk factors). The median OS from the time of gefitinib treatment for the good, intermediate, poor, and very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3 months, respectively (P < .001).

CONCLUSIONS:

This prognostic model based on easily available clinical variables would be useful to identify patients who might derive more benefit from gefitinib treatment and to make decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society.     

吉非替尼对于化疗失败的晚期肺腺癌的疗效及生存观察

目的：观察吉非替尼在化疗失败的晚期肺腺癌中的疗效、生存时间及影响因素。方法：收集２１例初始化疗失败的转移性肺腺癌,应用吉非替尼２５０ｍｇ口服,每日１次,直至出现有客观证据的病情进展,或出现不可耐受的不良反应。用Ｋａｐｌａｎ-Ｍｅｉｅｒ法拟定生存曲线,采用Ｌｏｇｒａｎｋ检验分析生存因素。结果：２１例患者中ＣＲ３例（１４.３％）,ＰＲ例８（３８.１％）,ＳＤ３例（１４.３％）,ＰＤ７例（３３.３％）。客观缓解率为５２.４％,疾病控制率为６６.７％。中位无进展生存时间（ＰＦＳ）为６个月,中位生存时间（ＯＳ）为８个月。１年生存率为３３.３％（７／２１）,２年生存率为９５％（２／２１）。好的ＰＳ评分与生存期延长显著相关（Ｐ＜０.０１）。结论：吉非替尼对既往化疗失败的晚期肺腺癌疗效好,能有效改善生存时间,体力状态评分与吉非替尼治疗的生存时间相关。     

Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment

Background

The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research is being carried out to discover the molecular mechanisms underlying this resistance. In comparison, few studies have been conducted to find out about the clinical characteristics of acquired resistance in the patients who had responded to an EGFR-TKI. Herein we investigated clinical characteristics of NSCLC patients who experienced acquired resistance during gefitinib therapy.

Patients and methods

We reviewed NSCLC patients who showed a clinical benefit from initial gefitinib therapy. All clinical data were obtained from 11 centers of Korean Molecular Lung Cancer Group (KMLCG). The clinical manifestations of acquired resistance, time to progression (TTP), and post-progression survival (PPS) after gefitinib failure were analyzed retrospectively.

Results

A total of 417 patients were recruited. Median TTP was 10.2 months (95% CI, 9.5–10.9). TTP showed a significant longer duration in female, non-smoker, and patients with adenocarcinoma. At the time of acquired resistance, 63.3% of the patients showed symptomatic deterioration. Sites of disease progression were as follows: primary lung lesion in 58.4%, previous metastasis in 38.3%, and new metastasis in 54.2%. Patients with EGFR wild type showed a tendency of higher frequency in symptomatic deterioration and newly development of CNS metastasis compared with patients with EGFR mutation. There was a significant difference in newly development of lung metastasis between patients with exon 19 deletion and those with L858R mutation (41.4% vs. 6.3%, p = 0.02). PPS was 8.9 months (95% CI, 7.4–10.4). Smoking history, PS, new CNS lesion and subsequent chemotherapy were independent factors for PPS.

Conclusion

This study suggests that clinical manifestations of acquired resistance may be different according to EGFR mutation status and EGFR mutation genotype. In addition, subsequent chemotherapy confers clinical benefit in terms of PPS in NSCLC patients who experienced acquired resistance after gefitinib therapy.     

贝伐单抗联合化疗治疗晚期多程治疗失败后的非小细胞肺癌临床观察

背景与目的:晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者多程治疗失败后,目前尚无标准的化疗方案。本研究旨在观察贝伐单抗联合化疗治疗晚期NSCLC多程治疗失败后的疗效和安全性。方法:2010年1月—2011年2月经病理证实符合入选标准的35例晚期NSCLC患者,接受贝伐单抗联合化疗方案治疗。化疗2个周期后按照实体瘤疗效评价标准(RECIST 1.0)评价疗效。按照美国国立癌症研究所制定的通用药物毒性标准3.0版评价不良反应。结果:35例患者中,30例完成2个周期以上的化疗,32例病例可评价疗效,总体PR 7例,SD 18例,PD 7例,RR为21.9%(7/32),DCR为78.1%(25/32);中位PFS为3个月,中位OS为8个月。与贝伐单抗相关的不良反应以高血压、蛋白尿和出血多见,其中多为Ⅰ、Ⅱ级,Ⅲ、Ⅳ级少见。结论:贝伐单抗联合化疗对晚期多程治疗失败后的NSCLC有一定的抗肿瘤活性和较高的疾病控制率,安全性较高,临床受益率高,是一种有临床应用前景的治疗方法。     

Prognostic factors in previously treated non-small cell lung cancer patients with and without a positive response to the subsequent treatment with gefitinib

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been reported to have a certain anti-tumor effect in previously treated patients with non-small cell lung cancer (NSCLC). However, the prognostic factors in those patients with and without a positive response to gefitinib treatment remain unclear. A retrospective chart review was performed in 131 advanced NSCLC patients who received 250 mg of gefitinib as either a second-line or even later stage treatment from July 2002 to December 2005. The clinical factors including age, gender, performance status (PS), stage, histology, the number of prior types of chemotherapy, and the response to first-line chemotherapy were analyzed. One and 38 patients experienced a complete and partial response, respectively, to gefitinib treatment with an overall response rate of 30%. The median survival time (MST) of all patients receiving gefitinib treatment was 10 months while the MST was 28 months in the 39 gefitinib responders and 6 months in the 92 non-responders. Among the 39 gefitinib responders, the predominant prognostic factor was found to be the effectiveness of the first-line chemotherapy. The MST of the 20 patients with a response to the first-line chemotherapy was 32 months while the MST of the 19 patients without a response to the chemotherapy was 22 months (p=0.025). Among the 92 gefitinib non-responders, the predominant prognostic factor was the PS (p<0.001). The effectiveness of the first-line chemotherapy was therefore found to be a prognostic factor in the gefitinib responders with previously treated NSCLC, while the PS was shown to be a prognostic factor in the gefitinib non-responders.     

Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib

A high incidence of interstitial lung disease (ILD) has been reported in patients with non-small cell lung cancer (NSCLC) treated with gefitinib in Japan. We retrospectively analyzed 112 patients with advanced NSCLC who received gefitinib monotherapy. Univariate and multivariate analyses were used to identify risk factors for gefitinib-related ILD and predictive factors for tumor response to gefitinib. The incidence of ILD was 5.4%, and it was higher in the patients with pre-existing pulmonary fibrosis (33% versus 2%; P < 0.001). The results of a multivariate analysis showed that pulmonary fibrosis was a significant risk factor for ILD (odds ratio: 177, 95% confidence interval: 4.53-6927, P = 0.006). The response rate was 33% in the 98 evaluable patients and higher in women (53% versus 23%; P = 0.003), patients with adenocarcinoma (38% versus 6%; P = 0.010), never-smokers (63% versus 18%; P < 0.001), and the patients with no history of thoracic radiotherapy (39% versus 13%; P = 0.015). The results of a multivariate analysis showed that the predictors of tumor response were "no history of smoking" and "no history of thoracic radiotherapy". Never-smokers had a significantly longer survival time than smokers (P = 0.007). Although gefitinib therapy confers a clinical benefit on patients with advanced NSCLC, especially on women, patients with adenocarcinoma, never-smokers, and patients with no history of thoracic radiotherapy, it also poses a high risk of ILD, especially to patients with pulmonary fibrosis. The risk-benefit ratio must be carefully considered.     

加速康复外科理念在行腹腔镜膀胱根治性切除术患者围术期中应用的临床观察#br#

目的探讨加速康复外科（ERAS）理念在腹腔镜膀胱根治性切除中应用的有效性和安全性。 方法收集2015年6月至2017年6月潍坊市人民医院收治的58例膀胱癌患者,分为传统组（n=28）和ERAS组（n=30）。比较两组患者的手术时间、手术出血量、术后排气时间、术后重度疼痛的发生数、麻醉苏醒时间、盆腔引流时间、术后住院天数以及术后并发症的发生情况。 结果ERAS组和传统组手术时间分别为（1722±379）min和（1873±218）min;术中出血量分别为（1597±465）ml 和（1771±469）ml,差异均无统计学意义（P＞005）。ERAS组和传统组麻醉苏醒时间分别为（254±54）min和（417±98）min;术后排气时间分别为（16±07）d和（22±07）d;盆腔引流时间分别为（25±11）d和（50±16）d;术后住院天数分比为（76±14）d和（110±18）d;术后疼痛VAS评分＞7分发生率分别为100％（3／30）和429％（12／28）;两组差异均有统计学意义（P＜005）。ERAS组1例刀口液化,1例发生肾结石;传统组2例肠梗阻,1例发生坠积性肺炎,1例发生肾结石。两组患者中均无尿瘘患者。 结论加速康复外科理念在腹腔镜下膀胱根治性切除术患者中的临床应用是安全、有效的,可加速患者的术后康复,值得临床推广应用。     

Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib

IntroductionSalvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non–small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies.Materials and MethodsThis study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non–small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate.ResultsTwenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively.ConclusionThese results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.     

吉非替尼对晚期非小细胞肺癌患者生活质量的改善

Objective  

The aim of this study was to evaluate the effect of gefitinib on improvement of quality of life (QoL) of patients with advanced non-small cell lung cancer (NSCLC).     

Survival outcome and predictors of gefitinib antitumor activity in East Asian chemonaive patients with advanced nonsmall cell lung cancer

BACKGROUND: Chemonaive patients had higher response rates than chemotherapy-treated patients in previous analyses of East Asian patients with advanced nonsmall cell lung cancer. The survival outcome and the predictors for antitumor activity in chemonaive patients who received gefitinib as first-line treatment are unclear. METHODS: Clinicopathologic predictive factors, objective tumor responses, and the survival of consecutive patients with advanced, chemonaive nonsmall cell lung cancer who received gefitinib as first-line treatment were collected and analyzed. Multivariate analysis was conducted to determine independent predictive factors for gefitinib antitumor efficacy. RESULTS: One hundred ninety-six patients (112 males and 84 females) were analyzed. Ninety-six patients (49%) were never smokers. One hundred forty-four patients (73%) had adenocarcinoma or bronchioloalveolar carcinoma histology. One hundred twenty patients had an Eastern Cooperative Oncology Group performance status 0 to 2. Eighty-three patients (42%; 95% confidence interval, 36-49%) had an objective tumor response. An additional 35 patients had stable disease (disease control rate, 61%). The tumor response rate was 52% in patients who had a good performance status. Female gender, nonsmoking status, and adenocarcinoma histology all were independent predictors of response or disease control in multivariate analysis. The median survival was 11.1 months, and the 1-year survival rate of patients who had a good performance status was 47.5%. CONCLUSIONS: The response rate to gefitinib was high in East Asian chemonaive patients with advanced nonsmall cell lung cancer. Female gender, adenocarcinoma histology, and nonsmoking status all were independent predictors of gefitinib response. The survival outcome of these patients was similar to that of patients who initially received chemotherapy.     

A Phase II trial of topotecan and gemcitabine in patients with previously treated,advanced nonsmall cell lung carcinoma

BACKGROUND: Multiple trials have been performed to evaluate second-line clinical chemotherapy in patients with advanced nonsmall cell lung carcinoma (NSCLC). However, no single agent or combination has demonstrated superior activity. METHODS: Patients with advanced NSCLC who had already received one chemotherapeutic regimen were treated with topotecan (0.75 mg/m(2) over 30 minutes, Days 1-5) and gemcitabine (400 mg/m(2) over 30 minutes, Days 1 and 5) every 21 days. RESULTS: Of 35 patients who were treated, 4 (11%) achieved a partial responses and 8 (23%) hadstable disease for at least four courses of treatment. The response rate for patients with refractory disease (progressing during frontline chemotherapy) was 18% (3 of 17) with 18% having stable disease for at least four courses of treatment. The median survival of the entire group was 7 months (range, 1.5-44 months) and 20% (7 of 35) of patients were alive 1 year from the initiation of topotecan and gemcitabine treatment. Patients with refractory disease had a median survival of 4(1/2) months, with 6-month and 1-year survival rates of 47% and 18%, respectively. During Course 1, five patients (14%) developed Grade IV neutropenia and three patients (9%) developed Grade IV thrombocytopenia. Nonhematologic toxicity was relatively mild, with one patient developing Grade III side effects (fatigue) and eight patients (23%) developing Grade II nonhematologic side effects. CONCLUSIONS: The combination of topotecan and gemcitabine demonstrated antitumor activity with a modest side effect profile in patients with advanced, previously treated NSCLC.     

Smoking affects treatment outcome in patients with advanced nonsmall cell lung cancer

BACKGROUND: The purpose of the current study was to determine whether smoking during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer (NSCLC) affects treatment outcome. METHODS: The authors reviewed the medical records of patients with NSCLC (AJCC Stage III or IV) who were treated with frontline chemotherapy or chemoradiation therapy at the University of Texas M. D. Anderson Cancer Center between January 1993 and December 2002. Treatment type, response, progression-free survival, and overall survival (OS) were correlated with patient demographic characteristics, clinical features, and smoking habits at the time of diagnosis and during therapy. RESULTS: Of 1370 patients who were eligible for analysis, 497 received chemoradiation therapy and 873 received chemotherapy. In the chemoradiation group, 6% of patients were never-smokers, 45% were former smokers, and 49% were current smokers. Multivariate analysis demonstrated no prognostic effect of smoking status on treatment response or OS rates in the chemoradiation therapy group. In the chemotherapy group, 16% of patients were never-smokers, 42% were former smokers, and 42% were current smokers; 20% of patients continued to smoke during therapy. Never-smokers had higher response rates (19% vs. 8% vs. 12%; P=.004) and lower rates of progressive disease (49% vs. 65% vs. 66%; P=.002) than former and current smokers, respectively. The OS rates were found to be higher among never-smokers (P<0001), women (P=.002), and those with a better Eastern Cooperative Oncology Group (ECOG) performance status (P<.0001). The multivariate Cox model indicated that with adjustment for age, gender, stage of disease, and ECOG performance status, the hazard ratio was 1.47 for former smokers (P=.003) and 1.55 for current smokers (P=.0004). Active smoking during therapy did not appear to impact outcome. CONCLUSIONS: Never-smokers were found to have an improved outcome over smokers when treated with chemotherapy.     

吉非替尼治疗化疗失败的晚期非小细胞肺癌临床观察

目的：评价吉非替尼治疗化疗失败的晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法：对68例化疗失败的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250mg,qd,口服,至病情进展或出现不可耐受的不良反应。结果：68例患者中,CR 1例,PR 20例,SD 23例,PD 24例。有效率30.88%（21/68）,疾病控制率为64.71%（44/68）;全组中位疾病进展时间（TTP）为5.2个月,中位生存时间为9.3个月,1年生存率为52.94%（36/68）。与药物相关的不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,皮疹发生率为26.47%（18/68）,腹泻发生率为19.12%（13/68）,多在用药后1周内出现,症状轻不需特殊处理。1例出现Ⅰ度转氨酶升高。结论：吉非替尼治疗化疗失败的晚期非小细胞肺癌安全有效,不良反应轻微,患者耐受性和依从性良好。     

吉非替尼治疗化疗失败的晚期非小细胞肺癌临床观察

目的:评价吉非替尼治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应。方法:对68例化疗失败的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250mg,qd,口服,至病情进展或出现不可耐受的不良反应。结果:68例患者中,CR 1例,PR 20例,SD 23例,PD 24例。有效率30.88%(21/68),疾病控制率为64.71%(44/68);全组中位疾病进展时间(TTP)为5.2个月,中位生存时间为9.3个月,1年生存率为52.94%(36/68)。与药物相关的不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,皮疹发生率为26.47%(18/68),腹泻发生率为19.12%(13/68),多在用药后1周内出现,症状轻不需特殊处理。1例出现Ⅰ度转氨酶升高。结论:吉非替尼治疗化疗失败的晚期非小细胞肺癌安全有效,不良反应轻微,患者耐受性和依从性良好。     

吉非替尼治疗复治、晚期非小细胞肺癌的临床分析

目的:观察晚期非小细胞肺癌(NSCLC)患者接受吉非替尼(gefitinib)治疗后的生存期、缓解率、疗效。方法:分析2000年12月-2003年10月美国M.D.Anderson癌症治疗中心与上海市胸科医院接受吉非替尼250 mg/d口服治疗的共175例晚期NSCLC患者。用Kaplan-Meier及logrank进行生存分析和比较,并用Cox多因素回归分析生存相关因素。用χ2检验比较不同因素在缓解率及疾病控制方面有无差异,logistic多因素回归分析疾病控制率、缓解率的相关因素。结果:175名患者的中位生存期(MST)为6.9个月(95%CI:4.19~9.61);中位无疾病进展时间(PFS)为3.47个月(95%CI:2.67~4.27)。Cox多因素分析显示性别(P=0.002)、年龄(P<0.001)、治疗前血红蛋白水平(P=0.034)、PS评分(P=0.019)、既往化疗方案次数(P=0.013)、病理类型(P=0.030)是影响生存的独立因素。性别(P=0.002)、PS评分(P=0.013)是影响PFS的独立因素。所有患者的缓解率为10.14%;疾病控制率为40.54%。影响缓解率与疾病控制率的多因素分析提示性别(P=0.041)、年龄(P=0.035)、吸烟情况(P=0.038)是影响缓解率的独立因素,而性别是影响疾病控制率的独立因素(P=0.036)。结论:吉非替尼治疗复治、晚期NSCLC患者是安全、有效的。     

吉非替尼一线治疗晚期非小细胞肺癌临床观察

为观察吉非替尼(Iressa)对初治的晚期非小细胞肺癌(NSCLC)的疗效及毒副反应,选取20例晚期NSCLC患者进入研究,所有患者均未接受过化疗,吉非替尼剂量为250mg/次,口服,1次/d,全组中位服药持续时间为10个月。结果:20例患者均可评价,获得CR2例(10.0%)、PR3例(15.0%)、SD6例(30.0%)、PD9例(45.0%),总的疾病控制率为55.0%;疾病相关症状改善率为75.0%。与药物相关的不良反应依次为:皮疹9例(45.0%),腹泻6例(30.0%),恶心4例(20.0%),皮肤干燥5例(25.0%),未观察到间质性肺炎病例。初步观察结果显示,吉非替尼对晚期NSCLC具有较好的疗效,不良反应轻微,可以考虑作为一些体质较差、不能耐受手术、放疗或化疗的NSCLC患者的一线治疗。     

Breast cancer resistance protein (BCRP) affected acquired resistance to gefitinib in a "never-smoked" female patient with advanced non-small cell lung cancer

Development of acquired resistance to gefitinib after an initial good response is common. Recently, it was reported that this acquired resistance is related to a secondary mutation associated with a substitution of threonine by methionine at codon 790 (T790M) of the epidermal growth factor receptor (EGFR) gene. In this report, we present a "never smoking" woman with advanced lung cancer who showed acquired resistance to gefitinib, and analysis of autopsy samples revealed no evidence of EGFR mutations in either exons 18-21 or codon 790, and positive immunostaining for breast cancer resistance protein (BCRP). We describe, for the first time, a case in which expression of BCRP was associated with acquired resistance to gefitinib, independent of EGFR mutations.