易瑞沙在晚期非小细胞肺癌化疗失败后的作用

目的探讨选择性表皮生长因子受体酪氨酸激酶抑制剂易瑞沙(IRESSA)单药治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应。方法既往化疗失败的Ⅳ期NSCLC患者52例,其中二线治疗失败者占77.0%。IRESSA250mg,口服,每日1次,服用至病情进展或出现不可耐受不良反应。患者分别在治疗后1个月、3个月及以后每2个月复查。结果本组52例均可评价疗效,其中PR11例,NC17例,PD24例,有效率21.2%,稳定率32.7%,疾病控制率(PR NC)为53.8%,无CR。中位肿瘤进展时间(TTP)为3.5个月。随诊>12个月的患者22例,1年生存率为31.8%,肿瘤相关症状缓解率为52.9%。常见不良反应为Ⅰ、Ⅱ度皮肤改变和腹泻,Ⅲ度不良反应占7.6%,其中1例因转氨酶升高结束治疗。结论IRESSA单药对化疗失败的晚期NSCLC疗效明确,并可用于一般状况评分较差的患者,不良反应较轻,是二、三线用药的良好选择。     

易瑞沙治疗晚期非小细胞肺癌的临床获益分析

目的:探讨选择性表皮生长因子受体抑制剂易瑞沙(IRESSA)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效及不良反应。方法:对既往化疗失败或不能耐受拒绝化疗的晚期NSCLC患者23例,单药IRESSA250mg,口服,每日1次,服用至病情进展或出现不可耐受的不良反应。患者分别在治疗后30、90d对其疗效及不良反应进行观察统计。结果:23例中22例可评价疗效,其中CR1例,PR6例,SD10例,PD5例,有效率31·8%(7/22),患者疾病控制率(CR+PR+SD)77·3%(17/22)。治疗后30d肿瘤相关症状缓解率为73·9%(17/23)。Karnofsky评分,治疗前总分数900,人均39·1;治疗后总分数1380,人均60;治疗前后比较差异有统计学意义,t=-3·18,P=0·004。常见不良反应为腹泻和皮肤改变,Ⅳ级占4·3%(1/23)。结论:IRESSA单药对化疗失败或不能耐受的晚期NSCLC疗效确切,改善症状明显,用药方便,不良反应轻。     

晚期NSCLC一线化疗疾病控制与生存关系的分析

目的回顾性分析一线化疗疾病控制（DCR）与进展（PD）患者之间生存的差别,探讨DCR可否预测生存。方法本文回顾性分析本院一线含铂联合化疗86例ⅢB期/Ⅳ期非小细胞肺癌（NSCLC）患者,化疗的疗效按WHO标准分为CR,PR,SD,PD。结果一线化疗后DCR共64例（74.4%）[其中CR 0例,PR 30例（34.9%）,SD 34例（39.5%）],PD 22例（25.6%）。DCR和PD患者中位生存期（MST）有统计学意义,为14.2月和5.1月（P〈0.001）。CR＋PR和SD患者MST有统计学意义,为15.0月和11.0月（P=0.030）。COX多因素回归分析显示一线化疗疾病控制（P=0.017）,ECOG评分（P=0.046）是总生存的独立预后因素。结论本研究提示晚期NSCLC患者一线化疗疾病控制患者其生存较进展患者好,疾病控制比化疗有效似乎更能反映化疗疗效,预测生存期。     

吉非替尼治疗非小细胞肺癌优势人群的临床观察

目的观察吉非替尼(ZD1839,IRESSA)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)优势人群的疗效。方法对2008年1月至2009年6月间接受了吉非替尼(250 mg/d,口服)治疗的48例晚期NSCLC患者的客观疗效及不良反应进行观察,分析疾病缓解率及疾病控制率的相关因素。结果 48例患者中CR 1例,PR 16例,SD 22例,PD9例,疾病缓解率为35.4%,疾病控制率为81.3%,中位生存期(median survival time,MST)为8个月(95%CI,6～9个月)。结论选择优势人群针对性地使用吉非替尼,可获得较高疗效,并有助于指导吉非替尼的个体化治疗。     

易瑞沙治疗化疗失败的晚期非小细胞肺癌疗效分析

目的 探讨易瑞沙(Irssa)单药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 经TP和NP/GP方案化疗失败的Ⅳ期NSCLC患者10例,口服易瑞沙250 mg,1次/d,至病情进展或出现严重不良反应.结果 10例患者中CR 3例,PR 5例,NC 2例,有效率80.0%.有效者均不吸烟,5例为女性,3例男性均为肺泡细胞癌.不良反应7例有皮肤改变表现(脱屑、痤疮),1例有轻度腹泻.1例CR和1例PR患者在服药14个月和10个月后出现复发和新病灶.结论 易瑞沙能有效缓解晚期化疗失败的女性NSCLC及不吸烟的男性肺泡细胞癌患者的病情.长期服用易瑞沙的患者可能出现获得性耐药.     

吉西他滨单药治疗老年晚期非小细胞肺癌患者36例

目的 观察吉西他滨单药治疗老年晚期非小细胞肺癌(NSCLC)患者的疗效及不良反应.方法 对36例ⅢB～Ⅳ期老年NSCLC患者应用吉西他滨单药化疗(1000mg/m2,第1、8天静脉滴注),21 d为1个周期.2个周期后分别按实体瘤疗效评价标准(RECIST)和美国国立癌症研究所(NCI)常见毒性反应标准评价不良反应,同时评估生活质量改善指标.结果 本组36例患者中,完全缓解(CR)0例,部分缓解(PR)10例,稳定(SD)15例,进展(PD)11例,有效(CR+PR)率为27.8%,临床受益(CR+PR+SD)率为69.4%.中位无进展生存(PFS)期为5.1个月,中位总生存(OS)期为7.8个月,1年生存率为30.6%(11/36).患者不良反应主要表现为以白细胞和血小板减少为主的骨髓抑制,白细胞减少Ⅰ～Ⅱ度发生率为44.4%(16/36),Ⅲ～Ⅳ度11.1%(4/36);血小板减少Ⅰ～Ⅱ度发生率为38.9%(14/36),Ⅲ度2.8%(1/36),无Ⅳ度减少发生.结论 采用吉西他滨单药治疗老年晚期NSCLC患者疗效好、不良反应轻、安全,可作为老年晚期NSCLC患者的一线治疗方案.     

吉西他滨单药治疗老年晚期非小细胞肺癌患者36例

目的 观察吉西他滨单药治疗老年晚期非小细胞肺癌(NSCLC)患者的疗效及不良反应.方法 对36例ⅢB～Ⅳ期老年NSCLC患者应用吉西他滨单药化疗(1000mg/m2,第1、8天静脉滴注),21 d为1个周期.2个周期后分别按实体瘤疗效评价标准(RECIST)和美国国立癌症研究所(NCI)常见毒性反应标准评价不良反应,同时评估生活质量改善指标.结果 本组36例患者中,完全缓解(CR)0例,部分缓解(PR)10例,稳定(SD)15例,进展(PD)11例,有效(CR+PR)率为27.8%,临床受益(CR+PR+SD)率为69.4%.中位无进展生存(PFS)期为5.1个月,中位总生存(OS)期为7.8个月,1年生存率为30.6%(11/36).患者不良反应主要表现为以白细胞和血小板减少为主的骨髓抑制,白细胞减少Ⅰ～Ⅱ度发生率为44.4%(16/36),Ⅲ～Ⅳ度11.1%(4/36);血小板减少Ⅰ～Ⅱ度发生率为38.9%(14/36),Ⅲ度2.8%(1/36),无Ⅳ度减少发生.结论 采用吉西他滨单药治疗老年晚期NSCLC患者疗效好、不良反应轻、安全,可作为老年晚期NSCLC患者的一线治疗方案.     

易瑞沙治疗晚期非小细胞肺癌的临床获益分析

目的：探讨选择性表皮生长因子受体抑制剂易瑞沙（IRESSA）治疗晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的临床疗效及不良反应。方法：对既往化疗失败或不能耐受拒绝化疗的晚期NSCLC患者23例，单药IRESSA 250mg，口服，每日1次，服用至病情进展或出现不可耐受的不良反应。患者分别在治疗后30、90d对其疗效及不良反应进行观察统计。结果：23例中22例可评价疗效，其中CR1例，PR6例，SD10例，PD5例，有效率31．8％（7／22），患者疾病控制率（CR＋PR＋SD）77．3％（17／22）。治疗后30d肿瘤相关症状缓解率为73．9％（17／23）。Karnofsky评分，治疗前总分数900，人均39．1；治疗后总分数1380，人均60；治疗前后比较差异有统计学意义，t=3．18，P=0．004。常见不良反应为腹泻和皮肤改变，Ⅳ级占4．3％（1／23）。结论：IRESSA单药对化疗失败或不能耐受的晚期NSCLC疗效确切，改善症状明显，用药方便，不良反应轻。     

GP方案治疗晚期非小细胞肺癌的临床观察

目的:观察健择 顺铂治疗晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的近期疗效.方法:自2000年6月到2005年6月,对60例晚期(Ⅲb期或Ⅳ期) NSCLC采用健择(GEM 1.0g/m2·d第1、8天)联合顺铂(CDDP 30mg/m2·d第1、2、3天)的方案化疗,21天重复,治疗两个周期后评价临床疗效.结果:60例患者中,2例CR,13例PR,26例SD,19例PD,总有效率为(CR PR)25.0%;鳞癌有效率35.3%,腺癌有效率23.1%;Ⅲb期有效率41.7%,Ⅳ期有效率22.2%,中位疾病进展时间(TTP)4.7月,1年生存率28.3%,中位生存时间9.2个月,主要毒副反应为骨髓抑制,其中白细胞下降至Ⅲ、Ⅳ度者达35.0%,血小板下降至Ⅲ、Ⅳ度者为10.0%,恶心呕吐发生程度达Ⅲ、Ⅳ度者为25.0%.结论:GP方案治疗晚期NSCLC临床效果较好,副作用较轻,适合晚期NSCLC患者使用.     

吉非替尼治疗化疗失败的晚期非小细胞肺癌疗效观察

目的观察吉非替尼治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法对32例化疗失败的晚期NSCLC患者给予吉非替尼250 mg,口服,每天1次,至病情进展或出现不可耐受的毒副反应。结果 32例患者中,CR 0例(0.00%),PR 8例(25.00%),SD 13例(40.62%),PD 11例(34.38%),有效率为25.00%,疾病控制率为65.62%,中位疾病进展时间为5.2个月,中位生存时间为9.3个月,1 a生存率为34.38%。结论吉非替尼治疗晚期NSCLC有较好的疗效,毒副反应可耐受。     

吉非替尼治疗晚期复治性非小细胞肺癌41例

Objective  We observe the curative effect, median survival time, time to progression, quality of life and adverse effect of patients with advanced refractory non-small cell lung cancer (NSCLC) after gefitinib (Iressa) treatment. Methods  Forty-one patients with grade IIIb to IV NSCLC previously treated with two chemotherapy including 85.4% of patients after second line therapy were chosen. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or toxic reaction has become intolerable. The patients were required to receive tumor evaluation before the treatment, one month, two month and every three months after Iressa administration. Results  All of 41 patients were evaluable for therapeutic effect. Without complete regression being observed, partial response rate (PR), stable disease (SD) and progression of disease (PD) were 43.9% (18/41), 34.1% (14/41) and 22.1% (9/41), respectively. The overall response rate was 43.9% (18/41) and disease control rate (PR + SD) was 78% (32/41). The response rate in male was 42.1%, while it in female was 45.5% (P > 0.05). Twenty-two of them (53.7%, 22/41) were still alive with 10.1 months of MST when the follow-up ended in November 2006. TTP and MST of patients who died was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% of all patients with 13 months of MST of PR patients. The Karnofsky enhanced 20 ± 5 after 28 days treatment without 3–4 degree of reactive toxicity. Conclusion  Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. Iressa is effective and safe for patients with poor performance status.     

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.     

Gefitinib treatment is highly effective in non-small-cell lung cancer patients failing previous chemotherapy in Taiwan: a prospective phase II study

Gefitinib has shown activity in the treatment of non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based combination chemotherapy and/or taxane treatment. Recently, gefitinib was documented to be more effective in an East Asian population, as well. Thus, we performed a gefitinib trial in Taiwanese patients to assess the efficacy of this regimen. Treatment consisted of gefitinib 250 mg one tablet daily until disease progression. Thirty-six patients were enrolled from January 2003 to September 2004. Gefitinib was second-line treatment in 10, third-line in 15, fourth-line in 9, and fifth-line in 2. All patients were evaluable for toxicity profile and response rate. After 8 weeks of treatment, three patients had a complete response (CR) and nine had a partial response (PR), with an overall response rate of 33.3% (95% confidence interval 17.9%-48.7%). All treatment-related toxicities were few and mild in severity, except that one patient suffered from reversible grade 3 interstitial pneumonitis. The median time to disease progression was 4.7 months, and the median survival was 9.5 months. The one-year survival rate was 45.1%. Survival was significantly better in those who responded to treatment (CR and PR) than in those who did not (median 20.1 vs. 4.7 months, p=0.0002). Survival was also better in those who demonstrated disease control using gefitinib (CR, PR, and stable disease) than in those who did not (14.1 vs. 1.4 months, p<0.0001). The authors conclude that daily gefitinib treatment has high activity, is well tolerated, and provides very good survival in Taiwanese NSCLC patients who have failed previous chemotherapy, especially in those who responded to gefitinib treatment or those whose disease was controlled by gefitinib treatment.     

Phase II study of nedaplatin and irinotecan followed by gefitinib for elderly patients with unresectable non-small cell lung cancer

PURPOSE: We conducted a phase II study of combination chemotherapy with nedaplatin (NP) and irinotecan (CPT) followed by gefitinib to determine the effects and toxicities in patients 70 years or older with unresectable non-small cell lung cancer (NSCLC). METHODS: Eligible patients were entered to receive 3 courses of 50 mg/m(2) NP and 60 mg/m(2) CPT on days 1 and 8 every 4 weeks and sequential gefitinib 250 mg po once a day was followed until tumor progression. RESULTS: Twenty-eight patients received NP and CPT combination chemotherapy. One patient achieved CR, 10 PR, 14 SD and 3 PD, and the response rate was 39.3%. Twenty-one patients received gefitinib 250 mg per day until tumor progression after completion of the NP and CPT chemotherapy. Two patients with SD after NP and CPT chemotherapy achieved PR. For the 3-drug combination, there were 13 responders and the overall response rate was 42.9%. Of the toxicities associated with NP and CPT chemotherapy, grade 4 neutropenia, and grade 3 febrile neutropenia were observed in 24 (33.8%) and 3 (4.2%) courses, respectively. Of the toxicities associated with gefitinib treatment, grade 3 anemia, and SGOT and SGPT elevation were observed in one patient (4.8%) each, respectively. The median survival time was 8.7 months, and the 1- and 2-year survival rates were 42.9 and 32.1%, respectively. CONCLUSION: NP and CPT followed by gefitinib is feasible for elderly patients with unresectable NSCLC.     

Gefitinib Treatment Is Highly Effective in Non-Small-Cell Lung Cancer Patients Failing Previous Chemotherapy in Taiwan: A Prospective Phase II Study

Abstract

Gefitinib has shown activity in the treatment of non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based combination chemotherapy and/or taxane treatment. Recently, gefitinib was documented to be more effective in an East Asian population, as well. Thus, we performed a gefitinib trial in Taiwanese patients to assess the efficacy of this regimen.

Treatment consisted of gefitinib 250 mg one tablet daily until disease progression.

Thirty-six patients were enrolled from January 2003 to September 2004. Gefitinib was second-line treatment in 10, third-line in 15, fourth-line in 9, and fifth-line in 2. All patients were evaluable for toxicity profile and response rate. After 8 weeks of treatment, three patients had a complete response (CR) and nine had a partial response (PR), with an overall response rate of 33.3% (95% confidence interval 17.9% - 48.7%). All treatment-related toxicities were few and mild in severity, except that one patient suffered from reversible grade 3 interstitial pneumonitis. The median time to disease progression was 4.7 months, and the median survival was 9.5 months. The one-year survival rate was 45.1%. Survival was significantly better in those who responded to treatment (CR and PR) than in those who did not (median 20.1 vs. 4.7 months, p=0.0002). Survival was also better in those who demonstrated disease control using gefitinib (CR, PR, and stable disease) than in those who did not (14.1 vs. 1.4 months, p<0.0001).

The authors conclude that daily gefitinib treatment has high activity, is well tolerated, and provides very good survival in Taiwanese NSCLC patients who have failed previous chemotherapy, especially in those who responded to gefitinib treatment or those whose disease was controlled by gefitinib treatment.     

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。     

Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial.

BACKGROUND: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.     

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.     

晚期非小细胞肺癌化疗和靶向治疗失败后的挽救性化疗

Objective:We conducted a prospective phase Ⅱ trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting.Methods:Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m2 intravenously for 30 min every 3 weeks until the toxicity was unacceptable or disease progressed.The response evaluation criteria in solid tumors (RECIST) guidelines were used for the evaluation of antitumor activity.Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0.Results:In total,31 patients were enrolled in this phase Ⅱ trial between February 2004 and December 2006,and 84 cycles (average 2.7 cycles) were given.We observed 4 partial responses (PRs) and 10 stable disease (SD) states in 31 eligible patients.The objective response rate was 12.9%,and the disease control rate was 45.2%.The median survival time (MST) was 10 months (95% Cl,5.05-15.08 months).The 1-year survival rate was 40.6%.The most common toxicities were neutropenia,anemia,and peripheral neuropathy that occurred as follows:45% of the patients experienced grade 3 or 4 neutropenia,29% experienced grade 3 anemia,and 25.8% had grade 3 peripheral neuropathy.No patient terminated docetaxel chemotherapy due to toxicity.Conclusion:Docetaxei is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.