吉非替尼与化疗治疗老年肺腺癌的随机对照研究

目的:观察吉非替尼治疗老年肺腺癌的疗效及不良反应方法:93例老年(≥65岁)肺腺癌患者采用随机数字表法随机分为两组,试验组47例使用吉非替尼(250 mg,po,Qd)治疗至病情进展或出现严重不良反应:对照组46例予以铂类药物为基础的两药联合方案或单药化疗。结果:吉非替尼组和化疗组的疾病缓解率分别为34.0%(16/47)和23.9%(11/46);疾病控制率分别为72.3%(34/47)和67.4%(31/46);疾病进展时间分别为6.7个月和5.8个月;中位生存时间分别为8.3个月(6个月～18个月)和7.1个月(5.5个月～16个月);两组生存情况采用Kaplan-Meier生存曲线分析,Log-rank检验两组生存时间差异没有统计学意义。吉非替尼组的不良反应依次为:皮疹36例(76.6%),腹泻22例(46.8%),粒细胞减少4例(8.5%),趾、指甲皲裂3例(6.4%)肝功能异常3例(6.4%),脱发2例(4.3%),呕吐1例(2.1%),多为Ⅰ度～Ⅱ度。化疗组的不良反应依次为:粒细胞减少44例(95.7%),呕吐39例(84.8%),脱发29例(63.0%),血小板减少25例(54.3%),贫血20例(43.5%),肝功能异常7例(15.2%),腹泻3例(6.52%)。通过对吉非替尼组进行亚组分析可见,不同性别、吸烟史有无、不同ECOG评分以及既往化疗方案数患者的缓解率及疾病控制率差异均没有统计学意义。结论:吉非替尼治疗老年肺腺癌有较好的疗效及安全性。     

吉非替尼一线治疗老年晚期肺腺癌临床观察

目的观察选择吉非替尼一线治疗老年晚期肺腺癌临床疗效及不良反应。方法 23例初治晚期肺腺癌、不吸烟、不适于全身化疗的老年患者接受吉非替尼治疗至疾病进展或不良反应不可耐受,观察近期疗效、体力状态改善情况及不良反应。结果 23例患者均可进行疗效评估,部分缓解率39.1%,疾病稳定率47.8%;治疗后65.2%的患者体力状态有所改善。主要不良反应为Ⅰ/Ⅱ度皮疹、乏力、腹泻。结论吉非替尼一线治疗老年晚期肺腺癌疗效确切,耐受性良好。     

吉非替尼一线与二线治疗EGFR突变型晚期非小细胞肺癌的疗效比较

目的：观察吉非替尼用于表皮生长因子受体（epidermal growth factor receptor,EGFR）突变型晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）一线或二线治疗对患者近期疗效及生存期的影响,分析吉非替尼的最佳治疗时机。方法：回顾性分析6l例EGFR突变型（外显子19或2l突变）晚期NSCLC患者的病历和随访资料,其中3l例患者接受吉非替尼一线治疗,30例患者接受吉非替尼二线治疗;应用Kaplan-meier法进行生存分析。结果：两组患者的性别（P=0．717）、年龄（P=0．849）、吸烟史（P=0．173）、病理类型（P=0．573）和临床分期（P=0．668）的差异无统计学意义。吉非替尼一线较二线治疗EGFR突变型NSCLC的近期有效率及疾病控制率明显提高（RR：64．5％VS23．3％,P=0．001;DCR：87．1％VS60．0％,P=0．016）。吉非替尼一线和二线治疗的中位无进展生存期分别为7．6和6．4个月（P=0．392）,中位总生存期分别为16．0和17．6个月（P=0．606）。另外,在最终获得疾病控制的患者中,吉非替尼一线治疗组为27例,二线治疗组为18例,2组中位无进展生存期及总生存期也无明显差异（PFS：8．0VS9．7个月,P=0．777;OS：17．0VS20．0个月,P=0．196）。结论：吉非替尼用于EGFR突变型晚期NSCLC患者,一线较二线治疗的近期疗效明显提高,但生存获益无明显差异。     

吉非替尼一线治疗晚期肺腺癌完全缓解1例

患者女性,80岁。因活动性气促半个月于2004年5月14日入院,既往无吸烟史。查体:呼吸稍促,KPS50分,左肺叩诊浊音,呼吸音减弱,心率100次/min,肝脾肋下未触及。肺部CT显示:左胸腔大量积液,胸腔穿刺抽出血性胸水,涂片见大量腺癌细胞。胸水排出后复查肺CT显示:左肺上叶肿物3.5cm×5.0cm,纵隔淋巴结转移,头颅CT、腹部B超未见转移灶。入院诊断:左肺腺癌、纵隔淋巴结转移、左胸腔积液(T4N2M0ⅢB)。入院后行左侧胸腔置管引流术,白介素-Ⅱ胸腔内注射及对症、支持疗法,临床症状略有缓解。因患者一般状态差,不能耐受放化疗,入院一周后给予吉非替尼2…     

埃克替尼治疗EGFR不同突变类型晚期肺腺癌的疗效分析

目的:回顾分析埃克替尼一线治疗EGFR不同突变类型肺腺癌患者的疗效是否存在差异.方法:收集福州肺科医院2016年01月至2017年12月确诊EGFR突变肺腺癌患者79例,EGFR 19外显子缺失33例,21外显子突变46例,均予口服"埃克替尼125 mg tid"治疗,进行生存期随访;应用χ2检验比较临床特征及临床疗效...     

吉非替尼治疗晚期肺腺癌25例临床观察

目的观察吉非替尼治疗晚期肺腺癌的近期疗效及毒副反应。方法 25例经放疗和化疗方案为"TP"或"GP"治疗无效或失败的肺腺癌患者。吉非替尼250 mg次/,口服,1次/d;服用至病情进展或出现不可耐受的毒副反应。结果本组25例患者均可评价疗效,完全缓解0例,部分缓解6例,稳定10例,进展9例,有效率24%,疾病控制率64%,中位生存期5.2个月(1~18个月),1年生存率52%;主要毒副反应是皮疹、皮肤瘙痒、皮肤干燥、腹泻和恶心,多为Ⅰ~Ⅱ度。结论吉非替尼治疗晚期肺腺癌有一定疗效,安全易耐受,无明显毒副反应。     

奥希替尼治疗不同表皮生长因子受体基因突变型晚期肺腺癌疗效分析

目的 分析一代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药后奥希替尼治疗不同EGFR基因突变的晚期肺腺癌临床疗效.方法 回顾性分析2015年1月至2019年10月郑州大学第一附属医院收治的82例EGFR敏感突变且第1代EGFR-TKIs耐药后基因检测T790M突变的晚期肺腺癌患者的临床资料.将50例19外...     

吉非替尼联合放疗治疗表皮生长因子受体突变型Ⅲ期肺腺癌患者的临床疗效

目的探讨口服吉非替尼联合三维适形放疗治疗表皮生长因子受体(EGFR)突变型Ⅲ期T 1~3N 2~3肺腺癌患者的临床效果。方法 2008年9月至2011年9月间在泰州市人民医院收治的78例EGFR突变型Ⅲ期T 1~3N 2~3肺腺癌患者中,按照随机数表法随机分为观察组和对照组,每组各39例。观察组患者采用吉非替尼联合三维适形放疗治疗;对照组患者给予吉非替尼治疗。观察并比较两组患者的完全缓解率、部分缓解率、中位生存期、无进展生存期和总生存期。结果观察组患者的完全缓解率显著高于对照组,中位生存期和无进展生存期显著长于对照组,差异均有统计学意义(均P<0.05);观察组患者的总生存期差异无统计学意义(P>0.05);观察组患者的不良反应发生率低于对照组(P<0.05),但所有患者均可耐受。结论对EGFR突变型Ⅲ期T 1~3N 2~3肺腺癌患者予以口服吉非替尼联合三维适应放疗治疗,可以获得良好的效果,值得临床推广。     

吉非替尼联合阿帕替尼一线治疗EGFR敏感突变的晚期非小细胞肺癌患者的疗效及安全性

目的:探讨吉非替尼联合阿帕替尼对比吉非替尼一线治疗EGFR敏感突变的晚期非小细胞肺癌患者的疗效及安全性,以明确阿帕替尼能否延迟吉非替尼的耐药时间。方法:选取2015年1月至2016年12月期间我院收治的EGFR敏感突变的晚期NSCLC患者50例进行回顾性分析,分为观察组和对照组,每组各25人。观察组:吉非替尼（0.25 g,口服,1次/日）联合阿帕替尼（0.5 g,口服,1次/日）;对照组:吉非替尼（0.25 g,口服,1次/日）。评价无进展生存时间、客观缓解率、疾病控制率和不良反应发生率。结果:观察组、对照组客观缓解率分别为76.0%、68.0%,疾病控制率分别为96%、92%。观察组的近期疗效似有优于对照组的趋势,但差异均无统计学意义。观察组中位PFS为14.3个月（95%CI 11.3~17.2）,对照组中位PFS为10.3个月（95%CI 8.5~12.0）,差异有统计学意义。观察组1年的PFS率为64%,95%CI为44.4%~83.6%;对照组为20%,95%CI为4.3%~35.6%。两组主要不良反应为皮疹、高血压、蛋白尿、消化道反应、手足综合征、肝酶升高、间质性肺炎以及乏力,最为突出的不良反应为皮疹,观察组发生率为88%,对照组为84%（P＞0.05）。两组主要不良反应有统计学差异的为1-4度的高血压（P=0.004）、蛋白尿（P=0.027）、手足综合征（P=0.040）,但严重不良反应（3-4度）均无统计学差异。结论:吉非替尼联合阿帕替尼一线治疗EGFR基因敏感突变的晚期NSCLC患者似乎是一种有效且耐受良好的治疗策略,可能延迟吉非替尼的耐药时间,还需大规模多中心的临床随机对照试验证实。     

A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations

This study was designed to prospectively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations and to explore the molecular factors affecting the efficacy of gefitinib. Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced (stage IIIB, IV, and recurrent) pulmonary adenocarcinoma. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20, and 21. Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and tolerability. Out of 147 screened patients, 45 pts (31%) had EGFR mutations and received gefitinib. The most common EGFR mutations were in-frame exon 19 deletions (29 pts, 64%) and L858R point mutation in exon 21 (15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. The ORR was 53.3% (95% CI, 38.6-67.9) and disease control rate (DCR) including stable disease was 86.7%. The median progression free survival (PFS) was 398 days and the median overall survival (OS) was 819 days. Treatment was well tolerated. Grade 3/4 adverse events (AEs) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients. There were no treatment-related Grade 4 AEs. Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out. The ORR and DCR were higher in patients with exon 19 deletions than those with L858R (62.1% vs 33.3%; P = 0.0705 and 96.6% vs 66.7%; P = 0.0062, respectively). All 4 patients with progressive disease had a L858R mutation. No secondary resistant mutations such as T790M mutation or insertions in exon 20 were found in those patients. In addition, OS was significantly better in patients with exon 19 deletions than those with L858R (24-month OS rate was 72.1% vs 32.0%, P = 0.0148). Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated. Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations (ClinicalTrials.gov number, NCT00344773).     

Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study

Introduction

Feasibility of gefitinib therapy in elderly patients with non–small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations.

Patients and Methods

We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile.

Results

Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%).

Conclusion

First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.     

Combination of chemotherapy and gefitinib as first‐line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial

To explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head‐to‐head study was performed to compare chemotherapy and gefitinib in combination or with either agent alone as first‐line therapy, in terms of efficacy and safety. A total of 121 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib combined with pemetrexed and carboplatin, pemetrexed plus carboplatin or gefitinib alone. The progression‐free survival (PFS) of patients in the combination group (17.5 months, 95% CI, 15.3–19.7) was longer than that of patients in the chemotherapy group (5.7 months, 95% CI, 5.2–6.3) or gefitinib (11.9 months, 95% CI, 9.1–14.6) group. The (hazard ratios) HRs of PFS for the combination group vs. chemotherapy and gefitinib groups were 0.16 (95% CI, 0.09–0.29, p < 0.001) and 0.48 (95% CI, 0.29–0.78, p = 0.003), respectively. The overall response rate (ORR) in the combination therapy group, chemotherapy group and the gefitinib group was 82.5%, 32.5% and 65.9%, respectively. The combinational strategy resulted in longer overall survival (OS) than chemotherapy (HR = 0.46, p = 0.016) or gefitinib (HR = 0.36, p = 0.001) alone. Our finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.     

吉非替尼(Iressa)在晚期肺腺癌的靶向治疗疗效观察

背景与目的 吉非替尼是选择性表皮生长因子受体酪氨酸激酶抑制剂,用于治疗非小细胞肺癌,特别是腺癌.本研究的目的是探讨吉非替尼在晚期肺腺癌中的疗效、副反应及影响因素.方法 收集26例晚期肺腺癌,应用吉非替尼250 mg口服,每日1次,直至出现任何疾病进展的客观证据或发生不可耐受的不良事件.定期复查,并进行生存分析.结果 26例患者中CR 1例(3.8%),PR 11例(42.3%),SD 9例(34.6%),PD 5例(19.2%).客观缓解率为46.2%,疾病控制率为80.8%.其中位无进展生存期为8.2个月,中位总体生存期为10.4个月,1年生存率为31.6%.年龄(＜70岁)、产生皮疹及CEA降低与较好的预后有密切关系,吉非替尼治疗级别及化疗次数等因素与预后无明显关系.用药前平均PS(ECOG)为3.0,用药后平均为1.8.平均症状缓解时间为5.2天.结论 吉非替尼是一种疗效好、副作用少、可以明显提高肺腺癌患者生活质量的靶向治疗药物,对没有化疗条件的腺癌患者,可以作为一线治疗首选用药.     

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective

The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.

Patients and methods

One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy.

Results

The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001).

Conclusions

Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.     

国产培美曲塞联合卡铂一线治疗老年Ⅳ期肺腺癌的临床研究

目的 探讨老年Ⅳ期肺腺癌患者采用国产培美曲塞联合卡铂一线治疗的疗效及安全性。方法 2009年7月至2011年12月收治49例老年Ⅳ期肺腺癌患者,给予国产培美曲塞联合卡铂一线化疗,具体方案为：培美曲塞500mg／m2 静滴,d1;卡铂 AUC=5 静滴,d1,21天为1个周期。每2个周期评价近期疗效并随访远期疗效,对相关指标的疗效进行分层分析,记录毒副反应。结果 48例患者可评价疗效,获PR 11例,SD 20例,PD 17例,有效率（RR）为22.9％,疾病控制率（DCR）为64.6％;48例可评价疗效的患者均获随访,中位无进展生存时间（PFS）为6.5个月（95％CI：5.7～7.3个月）,中位总生存时间（OS）为11.3个月（95％CI：10.6～11.9个月）;将年龄、性别、ECOG PS评分、吸烟状态、转移器官数目以及有无骨转移、恶性胸腔积液、脑转移共8个指标分层,其中ECOG PS评分、吸烟状态、转移器官数目分层间RR、PFS或OS的差异有统计学意义（P＜0.05）。49例患者的主要毒副反应为1～2级骨髓抑制和胃肠道反应,无1例需降低剂量强度或出现化疗相关性死亡。结论 国产培美曲塞联合卡铂化疗方案的临床获益显著且安全性高,是一线治疗老年Ⅳ期肺腺癌患者的较好选择。     

Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma

Background

Brain metastases (BM) are a common in patients with lung cancer. Although whole-brain radiation therapy (WBRT) is the standard therapy, it may have a risk of decline in cognitive function of patients. In this study, we evaluated the efficacy of gefitinib alone without radiation therapy for the treatment of patients with BM from lung adenocarcinoma.

Materials and methods

Eligible patients had BM from lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Gefitinib was given at 250 mg orally once a day until tumor progression or unacceptable toxicity.

Results

Forty-one patients were enrolled. The response rate was 87.8%. No patient experienced grade ≥4 toxicity. The median progression-free survival time was 14.5 months (95% CI, 10.2–18.3 months), and the median overall survival time was 21.9 months (95% CI, 18.5–30.3 months). In compared with L858R, exon 19 deletion was associated with better outcome of patients after treatment with gefitinib in both progression-free (p = 0.003) and overall survival (p = 0.025).

Conclusion

Favorable response of BM to gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a predictive and prognostic marker of patients with BM treated by gefitinib.     

EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition

Background

We aimed at investigating the outcomes of female patients with stage IIIB-IV adenocarcinoma of the lung according to EGFR and K-Ras mutational status.

Methods

One hundred and three consecutive female patients genotyped at a single Italian Institution were analyzed. Patients were planned to receive first-line platinum-based chemotherapy (CT) and a salvage treatment with anti-EGFR tyrosine-kinase inhibitors (TKIs) was proposed irrespective of tumor mutational status. EGFR (exons 18–21) and K-Ras (exon 2, codons 12–13) mutations were evaluated by real-time PCR and pyrosequencing. The association of mutational status with clinical variables and treatment benefit was investigated by chi-square test and log-rank test.

Results

EGFR and K-Ras mutations were found in 31 (30%) and 13 (15%) cases, respectively. Sixty-six patients received platinum CT: no correlation was observed between EGFR or K-Ras mutational status and response rate (RR) (p > 0.05). However, patients treated with first-line CT harboring EGFR activating mutations experienced a significantly reduced progression-free survival (PFS) in comparison with wild-type ones (4.4 vs. 6.4 months, respectively; HR 0.597, 95% CI 0.287-0.975; p = 0.048). Thirty-nine patients received salvage treatment with erlotinib: EGFR activating mutations were significantly correlated with RR (60% vs. 12.5%; p = 0.004) and PFS (11.4 vs. 4.5 months; HR 0.491, 95% CI 0.216-0.936; p = 0.044). Responses to erlotinib were not reported among women with K-Ras mutant tumors, while 50% of those with wild-type K-Ras achieved an objective remission (p = 0.296). Median PFS (3.5 vs. 8.8 months; HR 0.284, 95% CI 0.015-0.510; p = 0.010) and OS (3.9 vs. 19.8 months; HR 0.158, 95% CI 0.001-0.075; p < 0.001) were significantly shorter among K-Ras mutant patients treated with TKI.

Conclusions

In our population of Caucasian women with advanced lung adenocarcinoma we observed that the presence of EGFR activating mutations correlates with a significant reduction in the benefit from first-line platinum-based CT, emphasizing the importance of an upfront use of anti-EGFR TKIs in this patient subset. K-Ras mutations seem to correlate with a detrimental effect from anti-EGFR TKI, but this finding deserves further investigation.     

EGFR野生型肺腺癌患者一线化疗方案选择影响因素分析

目的 晚期肺癌一线化疗方案的有效率无明显差异,而在不良反应和药物经济学方面存在明显区别.本研究探讨晚期表皮生长因子受体(epidermal growth factor receptor,EGFR)野生型肺腺癌患者一线化疗方案应用状况并分析其原因.方法 回顾性分析广州医科大学附属第一医院2009-12-01-2014-11-30收治的738例晚期EGFR野生型肺腺癌患者5种不同一线方案应用状况和影响因素,观察其近期疗效和不良反应.结果 临床常用5种不同一线方案的患者例数分别为:吉西他滨含铂双药(GP组)358例,紫杉醇含铂双药(TP组)157例,多西他赛含铂双药(DP组)99例,培美曲塞含铂双药(PP组)93例,长春瑞滨含铂双药(NP组)31例.5组之间疗效差异无统计学意义,仅PP方案的疾病控制率较其他4个方案为优,x2 =4.01,P=0.038.5种方案不良反应:NP方案在3级以上白细胞减少方面明显高于其他方案,x2 =3.33,P=0.042;TP和DP方案在口腔炎、周围神经炎、3级及以上脱发的发生率方面明显高于其他方案,均P＜0.05;GP方案而在血小板减少及谷丙转氨酶升高方面明显高于其他方案,x2=3.21,P=0.043;PP方案在乏力方面明显高于其他方案,x2 =3.93,P=0.041;而5种方案在贫血、恶心、呕吐、腹泻、血肌酐升高和皮疹不良反应发生率差异无统计学意义.5种不同方案过去5年使用比例由高到低分别为,GP 48.51％＞TP 21.27％＞DP 13.41％＞PP12.60％＞NP 4.20％,这与5位制定化疗方案的主任医师对5个不同一线方案的平均评分排序完全一致.方案选择具体原因分析提示不良反应、使用便捷性、经济原因、医保政策4个因素是影响方案选择的主要原因,而疗效因素由于其本身差异并不明显,故并非是影响方案选择的主要原因.NP方案由于其不良反应和使用便捷性评分较低而总评分最低,而GP方案由于各方面均无明显劣势而总评分最高.结论 过去5年晚期EGFR野生型肺腺癌患者常用的5种一线方案使用率顺序依次为GP＞TP＞DP＞NP＞PP.5种方案疗效未见明显差异,并非是影响方案选择的主要原因.方案的选择与制定方案的具体医生推荐有明显相关性,而具体原因主要集中在不良反应、使用便捷性、经济原因和医保政策4个因素.     

Outcomes of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor mutation status treated with gefitinib

Aims: To evaluate the response and progression‐free survival (PFS) of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor (EGFR) mutation status treated with gefitinib. Methods: A retrospective analysis of consecutive patients with EGFR mutation unknown stage III or IV lung adenocarcinoma with EGFR mutation unknown treated with gefitinib until disease progression. Results: Of 71 patients, none had complete response while 26 (36.6%) had partial response and 26 (36.6%) had stable disease. Multivariate analysis showed the independent predictor of response to gefitinib was Eastern Cooperative Oncology Group (ECOG) performance status 1 (odds ratio [OR] 5.39, 95% confidence interval [CI 1.64–17.74]P = 0.006). The median PFS was 6.5 months and was significantly longer in female than male patients (39.0 vs 21.2 weeks; P < 0.001), never smokers vs smokers (32.3 vs 8.3 weeks, P = 0.001), and stage III versus stage IV disease (44 vs 24 weeks, P = 0.021). In a multivariate Cox proportional hazards model with age group, gender, ethnicity, smoking history, disease stage, ECOG performance status and prior cytotoxic chemotherapy as covariates, the independent predictors of longer median PFS were female gender (HR 95% CI 0.38 [0.22–0.66]; P < 0.001) and stage III disease (HR 95% CI 0.54 [0.30–0.98], P = 0.042). Conclusion: In our patients with EGFR mutation unknown advanced lung adenocarcinoma treated with gefitinib, the response rate was 36.6% and the median PFS was significantly longer in female patients, never smokers and patients with stage III disease.