吉非替尼治疗非小细胞肺癌51例疗效观察

目的探讨吉非替尼(Gefitinib,Iressa)治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及毒副反应。方法回顾性分析2004年3月至2006年3月沈阳军区总医院肿瘤科51例采用单药口服吉非替尼250mg每日1次治疗并获得随访的NSCLC复治患者的临床资料,评价其临床疗效、生存质量、中位生存期、疾病进展时间及毒副反应。结果病灶总缓解率为29.4%,总控制率为66.7%,临床症状改善率为62.7%,服药4周内KPS评分提高与治疗前相比差异有显著性意义。患者中位生存期为8.2个月,疾病进展时间为6.1个月,未出现Ⅲ~Ⅳ级毒性反应。结论吉非替尼可以显著改善NSCLC患者的临床症状及生存质量,且耐受性良好,是一种适合国人的分子靶向治疗药物。     

吉非替尼治疗非小细胞肺癌肺癌的现状及进展

非小细胞肺癌(NSCLC)的发病率和病死率高,治疗效果欠佳,5 a生存率低于5%.吉非替尼是一种合成的选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂, 通过与三磷酸腺苷竞争性结合抑制EGFR自磷酸化作用并阻断下游信号,使肿瘤细胞发生凋亡.自2002年上市以来,其治疗NSCLC的疗效已受到广泛关注.现就吉非替尼的结构特点及其分子作用机制、体内外抗肿瘤作用和临床应用进展综述如下.     

吉非替尼治疗高龄晚期非小细胞肺癌的疗效

目的探讨吉非替尼治疗高龄晚期非小细胞肺癌的疗效。方法对该院收治的62例高龄晚期非小细胞肺癌采用吉非替尼进行治疗,并对其疗效以及安全性进行评价。结果女性患者、腺癌患者、不吸烟以及未接受过化疗的患者治疗有效率以及疾病控制率明显优于男性患者、非腺癌患者、吸烟以及既往接受化疗的患者(P<0.05);ECOG评分为0～1分的患者中位PFS以及MST时间均长于评分≥2分的患者;病理分型、吸烟史、ECOG评分是影响患者疗效的相关独立影响因子(P<0.05)。结论吉非替尼对高龄晚期非小细胞肺癌具有良好的临床疗效,且安全性较高。病理分型、吸烟史、ECOG评分是影响患者治疗疗效的相关独立影响因素。     

关于吉非替尼治疗晚期非小细胞肺癌副反应分析

目的观察吉非替尼单药对化疗失败的晚期非小细胞肺癌的毒性反应。方法 41例既往化疗失败的非小细胞肺癌患者,口服吉非替尼250mg,每日1次直到病情进展或出现不可耐受的不良反应停药,同时评价疗效及药物不良反应。结果 41例患者中皮疹发生率60.98%;腹泻发生率26.83%,其中一例发生严重间质性肺炎。结论吉非替尼治疗晚期非小细胞肺癌疗效好,但有皮疹、腹泻、肝肾功能损伤、间质性肺炎等副作用。     

吉非替尼治疗老年非小细胞肺癌的临床研究

目的观察吉非替尼（gefitinib，ZD1839）治疗老年非小细胞肺癌（NSCLC）的治疗效果及不良反应。方法43例经病理学或细胞学确诊的老年NSCLC患者（≥60岁），应用吉非替尼（250mg，每日1次，口服）治疗直至病情进展或出现严重不良反应。结果43例可评价疗效患者：获得完全缓解（CR）2例（4．7％），部分缓解（PR）11例（25．6％），有效率（RR）为30．3％；稳定（SD）13例（30．2％）；进展（PD）17例（39．5％）。中位生存期（MST）10．3月，中位无疾病进展时间（TFP）8、1月。与药物相关的不良反应依次为：皮疹18例（41．9％），腹泻14例（32．6％），恶心10例（23．3％），关节痛9例（20．9％），肝功能异常8例（18．6％）。尚无因不良反应需停药者。结论吉非替尼治疗老年NSCLC疗效明确，不良反应较轻，耐受性较好。     

吉非替尼治疗老年晚期非小细胞肺癌的临床研究

目的 探讨表皮生长因子受体酪氨酸激酶抑制剂吉非替尼治疗老年晚期非小细胞肺癌(NSCLC)的疗效及不良反应. 方法 选择46例≥65岁老年晚期NSCLC患者,吉非替尼250 mg,口服,每日1次,服用至病情进展(PD)或出现不可耐受的不良反应.患者在治疗后每月进行复查. 结果 本组46例均可评价疗效,其中部分缓解(PR)12例(26.09%)、稳定(SD)20例(43.48%)、PD 14例(30.43%).疾病控制率(PR+SD)为69.57%.中位疾病进展时间(TTP)为3.8月,1年生存率为28.26%,肿瘤相关症状改善率为63.33%.常见不良反应为皮疹和腹泻,大部分为Ⅰ、Ⅱ度. 结论 吉非替尼单药治疗老年晚期NSCLC疗效明确,不良反应相对较小,患者耐受性好.     

吉非替尼治疗晚期非小细胞肺癌疗效观察

目的 探讨表皮生长因子酪氨酸激酶抑制剂-吉非替尼对晚期非小细胞肺癌(NSCLC)的治疗效果。方法 对66例应用Iressa(250mg／d)治疗的晚期NSCLC患者生活质量、生存期等临床资料，采用Logistic回归分析、x^2检验、t检验的方法进行统计学分析。生活质量评估依据欧洲癌症研究和治疗组织QLQ-C30和QLQ-Lcl3问卷中文版进行。结果 本组患者用Iressa治疗的有效率为33％(22／66)，疾病控制率(有效 稳定)为70％(46／66)。患者生活质量及相关临床症状QLQ．C30评分中各功能状态和综合生活质量评分的均值显著增加，改善率为91％～100％；QLQ-LC13评分中各项疾病相关症状评分的均值显著降低，改善率为73％～100％。药物的不良反应主要为Ⅰ级或Ⅱ级皮疹和腹泻，经对症处理可缓解。结论 吉非替尼用于晚期NSCLC治疗疗效确切，同时可改善患者的相关症状、提高生活质量。     

厄洛替尼治疗吉非替尼失败后晚期非小细胞肺癌的疗效

目的 评价厄洛替尼治疗吉非替尼失败后晚期非小细胞肺癌( NSCLC)的疗效及安全性临床研究.方法 选择12例既往口服吉非替尼有效,但后来又因病情进展而口服厄洛替尼的NSCLC患者,均予厄洛替尼150mg,每日1次口服,1个月后评价疗效及安全性.结果 口服厄洛替尼组12例病人无CR及PR病人,疾病控制率75％(9/12),肿瘤无进展生存期(PFS)4.1个月,症状缓解率75％,主要毒副反应为皮疹、腹泻.结论 对于吉非替尼治疗NSCLC失败后,采用厄洛替尼治疗可延长病人PFS时间,改善病人生存质量.     

CT灌注成像预测吉非替尼治疗非小细胞肺癌的敏感性

目的探讨非小细胞肺癌(NSCLC)患者CT灌注成像(CTP)参数特点对吉非替尼疗效的预测价值。方法回顾性分析29例经病理证实的晚期NSCLC患者应用吉非替尼治疗前的CT容积灌注资料及临床资料,根据RECIST标准将患者分为缓解组和未缓解组,对比分析两组治疗前病灶CT容积灌注参数。结果缓解组19例患者,未缓解组10例患者,缓解组血容量(BV)值、血流量(BF)值、表面通透性(PS)值高于未缓解组,缓解组肿瘤组织的对比剂平均通过时间(MTT)较未缓解组缩短(P<0.05)。结论 CTP可以量化反映肿瘤微血管的代谢功能,可以为预测吉非替尼治疗NSCLC的疗效提供参考。     

吉非替尼治疗晚期非小细胞肺癌的临床观察

目的 观察吉非替尼单药治疗晚期非小细胞肺癌的疗效与不良反应.方法 24例Ⅲ～Ⅳ期非小细胞肺癌患者口服吉非替尼(易瑞沙)250 mg/d,1次顿服,不限疗程,直至出现严重不良反应或因经济问题或死亡而终止.观察临床症状改善情况、不良反应,通过CT扫描判断疗效.结果 24例患者中完全缓解2例,部分缓解12例,稳定6例,进展4例,有效率为58.3%,疾病控制率为83.3%,主要不良反应为腹泻.结论 吉非替尼应用于放、化疗失败或不能耐受放、化疗的非小细胞肺癌患者是安全的,患者耐受性好.     

Palliative Hypofractionated Radiotherapy For Non-small-cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy

Aim

To investigate the effectiveness and toxicity of radiotherapy (RT) given as 17 Gy in 2 fractions, in patients with locally advanced non-small-cell lung cancer (NSCLC) previously treated by platinum-based chemotherapy (CHT) and the impact of total tumor volume (TTV) on symptoms control.

Materials and methods

Patients with inoperable NSCLC resistant to induction platinum-based CHT, who developed symptoms during or just after radiotherapy, were treated by 17 Gy in two fractions one week apart. In 12/28 patients a minimal response (up to 20% of TTV) and in 16/28 a stable or locally progressive disease had been recorded after induction CHT. In 26/28 patients, symptoms were present during-after CHT and before RT. The prognostic significance of pre-RT TTV on symptoms control and patients survival was also examined.

Results

We report on 28 patients. Response rates for the four main symptoms were: cough 13/19 (68%), haemoptysis 9/10 (90%), pain 8/14 (57%) and dyspnoea 5/13 (38%). Hematologic and local-thoracic toxicities were minimal. The median survival from the beginning of RT, for the whole group of patients was 9 months (95% CI:3.7-14.3), while for those patients with TTV<120 cc it was 12 months, and for those with TTV 120cc, it was 5.2 months. TTV was not suggested to influence symptoms control rate.

Conclusion

The two-fraction radiotherapy course is safe and effective in palliation of symptomatic non-small-cell lung cancer patients non-responding to induction CHT. Present data suggests that the TTV may influence survival time.     

吉非替尼在晚期肺腺癌的靶向治疗疗效观察

目的探讨吉非替尼在晚期腺癌中的疗效、副反应及影响因素。方法选择经病理证实的26例晚期肺腺癌病人．应用吉非替尼250mg口服，每日一次，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。并对结果进行生存分析。结果26例患者中CR1例（3．8％）．PR11例（42．3％），SD9例（34．6％），PD5例（19．2％）。客观缓解率为46．2％，疾病控制率为80.8％。其无进展生存期为8．2月，总体生存期10．4月，1年生存率31．6％．年龄（〈70岁），产生皮疹及CEA降低与预后好有密切关系，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PS（ECOG）为1.8。平均症状缓解时间为5．2天。结论吉非替尼是一个疗效好．副作用少。可以明显提高肺腺癌患者生活质量的一种靶向治疗药物。对没有化疗条件的腺癌患者．可以作为1线治疗首选用药。     

Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study Group experience

Background  Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma. Methods  We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy (250 mg/day), and whose smoking status was known. Tumour response and survival were evaluated and stratified by smoking status and gender. Results  Among the 260 patients, 157 were male (60%). Median pack-years was 40 (range 8–160) and 23 (range 1–74) in male and female smokers, respectively. Objective response was observed in 62 (23.8%) of the 260 patients, and 1-year overall survival and progression-free survival were 45.1 and 24.3%, respectively. Multivariate analysis revealed that smoking status (pack-years) was an independent predictive factor for response to gefitinib [odds ratio (OR) = 0.971, 95% confidence interval (CI) = 0.947–0.995; P = 0.0159] in male patients, but not in female patients (OR = 0.999, 95%CI = 0.957–1.042). Additionally, pack-years significantly influenced the overall survival in males (hazard ratio = 1.010; 95%CI = 1.002–1018, P = 0.0169), while differential survival of females was not significantly predicted by this factor (P = 0.7639). Conclusions  In male patients with lung adenocarcinoma, cumulative smoking significantly affected response and survival following gefitinib treatment, while in female patients, responsiveness to gefitinib was independent of smoking status. These results suggest that the influence of smoking habit on responsiveness to gefitinib is gender specific.     

Diagnostic Performance of 18F-FDG PET/CT for Lymph Node Staging in Patients with Operable Non-small-cell Lung Cancer and Inflammatory Lung Disease

As ¹⁸F-fluorodeoxyglucose (FDG) is taken up by inflammatory lymph nodes, it could be falsely interpreted as metastasis. Therefore, we evaluated the diagnostic ability of positron emission tomography/computed tomography (PET/CT) for lymph node staging of lung cancer when inflammatory lung disease coexisted. Patients with operable non-small-cell lung cancer and FDG-avid lymph nodes were retrospectively classified into two groups; those with inflammatory lung disease (ILD) and those without it (NILD). Receiver operating characteristic (ROC) curve analysis was performed for maximum standardized uptake value (SUVmax), pattern of FDG uptake, maximum Hounsfield unit, and size, and then the areas under the ROC curves (AUCs) were compared between subgroups. There were 124 patients (ILD/NILD = 38/86) and 396 FDG-avid lymph nodes (ILD/NILD = 140/256). The average number of FDG-avid lymph nodes was greater in ILD (3.7 vs. 2.9, p = 0.039), whereas the proportion of metastasis was higher in NILD (25.4% vs. 11.4%, p = 0.002). With all N1–N3 lymph nodes and the NILD group, the AUC values of all four parameters were significantly greater than 0.5 (p < 0.05), and SUVmax was the most valuable parameter for lymph node metastasis. However, in the ILD group, only the AUC value of SUVmax was significantly greater than 0.5. These results were reproduced when analyses were performed with N1–N2 lymph nodes. In conclusion, SUVmax was the most valuable PET/CT parameter for assessment of lymph node metastasis in patients with operable non-small-cell lung cancer. In addition, it was the only valuable parameter when inflammatory lung disease coexisted.     

Phase II Study of Troxacitabine (BCH-4556) in Patients with Advanced Non-Small-Cell Lung Cancer

Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS ≤ 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m²) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0–7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested. This work was supported by NCIC and BioChem Pharma Inc.     

Successful Treatment with Afatinib after Osimertinib-induced Interstitial Lung Disease in a Patient with EGFR-mutant Non-small-cell Lung Cancer

Osimertinib is the standard treatment for epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer. However, drug-induced interstitial lung disease (ILD) is recognized as a serious adverse event associated with EGFR-tyrosine kinase inhibitors (TKIs). We herein report a 78-year-old woman with stage IV lung adenocarcinoma harboring an EGFR L858R mutation on exon 21 who received rechallenge treatment with afatinib after osimertinib-induced ILD with an organizing pneumonia pattern. This is the first report of successful rechallenge with afatinib after osimertinib-induced ILD. Treatment with other EGFR-TKIs after osimertinib-induced ILD may be an option for subsequent therapy.     

Effect of Histologic Type on Recurrence Pattern in Radiation Therapy for Medically Inoperable Patients with Stage I Non-Small-Cell Lung Cancer

Japanese randomized trials showed that there was a significant impact on survival from stage I adenocarcinoma (AD) of the lung by adjuvant chemotherapy with uracil-tegaful after complete resection but there was no effect for patients with squamous cell carcinoma (SQ). The purpose of this study was to examine the correlation of tumor histology and clinical outcome of radiation therapy (RT) for stage I non-small-cell lung cancer (NSCLC) and to consider the necessity of adjuvant chemotherapy after RT for these patients. The subjects were 83 patients, 54 with SQ and 29 with AD; they had received definitive RT with the total dose ranging from 60 to 80 Gy with conventional fractionation at a daily dose of 2 Gy. The differences between SQ and AD with respect to survival and recurrence pattern were investigated. The 5-year overall survival and cause-specific survival rates were 26.5% and 49.1%, respectively. No difference in survival was observed between SQ and AD patients, and the recurrence rates were almost identical (44% for SQ and 45% for AD). However, the 5-year primary control rate of SQ was significantly poorer than that of AD (SQ: 61.5%; AD: 87.6%; p = 0.03). Conversely, the 5-year metastasis-free survival rate of SQ was significantly better than that of AD (SQ: 88.2%; AD: 53.0%; p = 0.005). The different failure pattern, according to tumor histology, indicates that taking into consideration the difference in their clinical behaviors would also be important for planning RT and surgery for early lung cancer. Presented in part at the 10th World Conference on Lung Cancer, Vancouver, British Columbia, Canada, August 10–14, 2003.     

紫杉醇联合顺铂不同给药剂量治疗老年晚期非小细胞肺癌的临床分析

目的本研究旨在比较不同剂量紫杉醇联合卡铂治疗老年晚期非小细胞肺癌(NSCLC)患者的毒副反应及疗效。方法 62例老年晚期NSCLC患者被分为结果低剂量和常规剂量两组,根据体表面积,前者给予70 mg/m2和20 mg/m2,第1、8天静滴3小时。后者给予90 mg/m2和25 mg/m2,第1、8天静滴3小时。21天为一周期,随访疗效和毒副作用。结果低剂量组和常规剂量组的总体有效率分别为45.5%与47.5%,差异没有统计学意义(P>0.05),常见的不良反应有骨髓移植、恶性呕吐、脱发等,其他不良反应,均可耐受。结论低剂量紫杉联合顺铂治疗老年晚期NSCLC疗效较好,毒副作用可以耐受,值得临床推广应用。     

甲地孕酮在晚期肺癌化疗中应用的临床观察

目的观察甲地孕酮(MA)在晚期肺癌化疗中的临床疗效。方法将56例晚期肺癌患者随机分为治疗组30例(化疗加MA)和对照组26例(单纯化疗),分析两组临床疗效。结果治疗组在KPS评分、进食增加、体重增加、疼痛缓解、骨髓抑制和恶心呕吐方面明显优于对照组,差异有统计学意义(P<0.05)。结论晚期肺癌化疗加用甲地孕酮能够改善患者的体质营养状况,增强对化疗的耐受力,减轻毒副反应。