老年晚期非小细胞肺癌的靶向治疗

非小细胞肺癌约占全部肺癌的85%,约70%患者在确诊时处于不能手术的局部晚期或已有转移,化疗是这些患者主要的治疗方法.     

局部晚期非小细胞肺癌预后因素评估

目的分析影响局部晚期非小细胞肺癌（NSCLC）3年生存率的预后因素。方法回顾性队列分析104例局部晚期NSCLC的病例资料；采用Kaplan—Meier方法分析单因素对生存率的影响，Log—rank检验比较生存率间的差异；多因素分析采用Cox比例风险模型。结果Kaplan-Meier方法单因素分析结果显示，14个预后相关因素中，Karnofsky评分（KPS评分）、体重减轻、临床分期、癌灶数目、N分期、细胞分化、治疗手段等7个因素对局部晚期NSCLC患者3年生存率有明显影响，经Log-rank检验，P〈0．05。在Cox比例风险模型分析结果中，KPS评分与临床分期2个因素对3年生存率影响显著，P〈0．01。结论KPS评分、体重减轻、临床分期、癌灶数目、N分期、细胞分化、治疗手段等7个因素对局部晚期NSCLC患者生存率有影响，而KPS评分、临床分期可作为独立因素对局部晚期NSCLC患者生存率产生影响。     

Preliminary Phase II Study of Adriamycin (ADM) in Patients with Non-Small Cell Lung Cancer (NSCLC)

A phase II study of adriamycin (ADM) (60 mg/m² was performedin 22 patients with non-small cell lung carcinoma (NSCLC). Therewere no responders in the 19 evaluable patients (16 with adenocarcinoma,two with squamous cell carcinoma and one with large cell carcinoma).The major side effects were alopecia (89%), leukocytopenia (73%),thrombocytopenia (58%) and upper gastrointestinal symptoms. Although ADM at 60 mg/m² did not appear to have sufficient antitumoractivity against NSCLC in this study, it is necessary to evaluatefurther the efficacy of ADM against NSCLC with another treatmentschedule.     

Management of Elderly Patients with Advanced Non-Small Cell Lung Cancer in Turkey

Objective: Non-small cell lung cancer is a disease that affects the elderly. However, most patients older than70 years are less likely to receive standard therapy than their younger counterparts and the aim of the presentstudy was to determine age-dependent variation in efficacy. Subjects and Methods: Between 2004-2008, 40consecutive patients older than 70 years received treatment for advanced non-small cell lung cancer. All wereevaluated for response and toxicity. Chemotherapy was either with cisplatin or carboplatin and double or singleagents (vinorelbine, gemcitabine). Docetaxel was used as a second line therapy in selected cases. Patients weregrouped according to age: group 1 (70-74 years), group 2 (≥ 75 years). Results: Except for 4 cases, all receivedchemotherapy, and 61 % were given a cisplatin-containing regimen. Second-line therapy was given to 42.5%and grades 3-4 neutropenia was seen in 17 (42.5%). Only one patient died due to neutropenic fever. Nephrotoxicitywas observed in 2 (5%) and one underwent hemodialysis. Overall survival was 10 months, with median survivalperiods for groups 1 and 2 of 13 and 10 months, respectively (p>.05). No differences were found regarding typeof chemotherapy administered or adverse events between the 2 groups. Conclusion: Patients older than 75years appear to deserve the same standard therapy for non-small cell lung cancer as that given to younger cases.     

不同化疗方案治疗老年晚期非小细胞肺癌的临床观察

目的比较不同化疗方案治疗老年非小细胞肺癌的疗效。方法回顾性分析接受化疗的老年晚期非小细胞肺癌61例的临床资料。结果 61例老年非小细胞肺癌的化疗有效率31.1%,KPS评分改善率37.7%。骨髓抑制：白细胞减少Ⅰ-Ⅱ度57.4%,Ⅲ-Ⅳ度6.6%;血小板减少Ⅰ-Ⅱ度47.7%;贫血Ⅰ-Ⅱ度33.4%。消化道反应：恶心呕吐Ⅰ-Ⅱ度29.3%,Ⅲ-Ⅳ度6.7%。未出现化疗相关死亡。结论本组化疗方案治疗老年晚期非小细胞肺癌疗效好,毒副反应可耐受;对于有较好器官功能的老年晚期非小细胞肺癌患者可考虑给予化疗。     

Platinum Re-Exposure as a Non-Small Cell Lung Cancer (NSCLC) Treatment Strategy in the Age of Immunotherapy

IntroductionImmunotherapy has prolonged the time that NSCLC patients are off platinum-based (PB) chemotherapy. However, the significance of the platinum-free-interval (PFI) is unclear. We evaluated whether an optimal PFI exists in NSCLC for PB re-exposure in contemporary treatment settings.MethodsWe conducted a retrospective cohort study of patients with metastatic NSCLC treated with 1st-line PB chemotherapy with or without immunotherapy. Using multivariable Cox models stratified by treatment strategies, we evaluated whether salvage PB vs. nonPB chemotherapy resulted in superior outcomes and whether this was modulated by the PFI.ResultsA total of 751 patients treated with salvage chemotherapy after PB chemoimmunotherapy were identified in 2 treatment strategy cohorts: 3rd-line after sequential chemotherapy and immunotherapy (Sequential Chemo IO, n = 604); 2ndline after chemoimmunotherapy (Concurrent ChemoIO, n = 147). An optimal PFI of 5 and 6 months was identified in the Sequential Chemo IO and Concurrent ChemoIO cohorts, respectively, but there was no overall survival or progression free survival advantage for PB vs. nonPB chemotherapy in long or short PFI groups.ConclusionAn optimal PFI was identified in this contemporary NSCLC cohort treated with two common immunotherapy-containing treatment approaches, but PFI threshold did not predict benefit from platinum re-exposure as it has in other malignancies.     

Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC)

IntroductionKRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.MethodsIn this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available.ResultsA total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti–programmed death 1, anti–PD-L1, or anti–cytotoxic T-lymphocyte associated protein 4 antibodies), including 162 (57.4%) with KRAS mutation, 27 (9.6%) with other mutations, and 93 (33%) with a wild-type phenotype, were identified. PD-L1 analysis was available for 128 patients (45.4%), of whom 45.3% and 19.5% had PD-L1 expression of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progression-free survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non–KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those with PD-L1 expression in less than 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression ≥50%).ConclusionFor patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICIs in KRAS-mutant NSCLC than it is in other types of NSCLC.     

吉西他滨单药治疗老年晚期非小细胞肺癌的临床观察

目的 观察吉西他滨单药治疗老年晚期非小细胞肺癌(NSCLC)的疗效及毒副反应.方法 观察组36例老年晚期NSCLC,年龄≥65岁,应用吉西他滨1000 mg/m2,静脉滴注,d1,8,每21d为1周期,至少2个周期.对照组26例老年晚期NSCLC给予最佳支持治疗(BSC).结果 吉西他滨治疗组有效率(RR)为27.78%,中位疾病进展时间5.4个月,中位生存期8.6个月,1年生存率36.11%;对照组有效率(RR)为0,中位疾病进展时间2.7个月,中位生存期4.6个月,1年生存率11.53%.观察组毒副反应较轻,无因毒副反应停药者.结论 吉西他滨单药治疗老年晚期NSCLC安全有效,可延长患者的生存时间,改善其生活质量;毒副反应可以耐受.     

Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer

Purpose: This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treatingpatients with non-small cell lung cancer (NSCLC). Methods: Clinical studies evaluating the efficacy and safetyof icotinib-based regimens with regard to response and safety for patients with NSCLC were identified usinga predefined search strategy. Pooled response rates of treatment were calculated. Results: With icotinib-basedregimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible forinclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985)with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III orIV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinibbasedregimens. Conclusions: This evidence based analysis suggests that icotinib based regimens are associatedwith mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.     

Phase II Trial of Oral Idarubicin in Advanced Non-Small Cell Lung Cancer (NSCLC)

The antitumoral activity and toxicity of a new daunorubicin analog (4-demethoxydaunorubicin, IMI30, Idarubicin) was tested in 20 consecutive patients with non-small cell lung cancer mostly pretreated with chemotherapy. The drug was administered orally at a dose of 15 mg/m² for three days every 3-4 weeks. There were no clinical responses. Hematological and nonhematobgical toxicities were mild.     

NP与NO方案治疗老年晚期非小细胞肺癌的对比观察

目的 比较长春瑞滨联合顺铂(NP)与长春瑞滨联合奥沙利铂(N0)方案治疗老年晚期非小细胞肺癌( NSCLC)的临床疗效和毒副反应.方法56例无法手术或术后复发转移的老年晚期NSCLC随机分为两组,分别给予NP和NO方案化疗,治疗2个周期后分别评价临床疗效和毒副反应.结果NP方案组总有效率为46.2%,NO方案组为50....     

150例老年晚期非小细胞肺癌不同治疗方案回顾性分析

背景与目的 老年晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)无标准治疗,本研究比较含铂双药联合化疗、多西他赛单药及最佳支持治疗三种方法治疗老年晚期NSCLC的疗效、毒副作用及中位生存时间,探索老年晚期NSCLC最佳治疗方法.方法 回顾性分析2003年3月-2007年3月我院接受含铂双药联合化疗、多西他赛单药化疗及最佳支持.冶疗(best support care,BSC)三种不同治疗方案的150例老年NSCLC患者.结果 含铂双药联合化疗有效率明显较多西他赛单药化疗高.分别为41.2%和20.0%(P＜0.05).含铂舣药化疗、多西他赛单药化疗和最佳支持治疗组中位生存期分别为10.7个月、9.2个月和6.3个月,tO生存率分别为39.7%.36.7%和17.3%.化疗组中位生存时间较最佳支持治疗组明显延长(P＜0.05),1年生存率较最佳支持治疗组明显提高(P＜0.05).含铂双药化疗和多两他赛单药化疗中位生存期及1年生存率无统计学差异(P＞0.05);Ⅲ-Ⅳ度骨髓抑制及消化道毒副作用发生率含铂双药组较多西他赛单药组明显增高(P＜0.05).结论 与最佳支持治疗比,化疗能明显延长老年晚期NSCLC中位生存期.提高1年生存率.含铂双药化疗有效率虽较多西他赛单药化疗高,但毒副作用较大,中位生存期及1年生存率无统计学差异,单药化疗应成为老年晚期NSCLC的标准治疗.     

吉西他宾单药治疗老年晚期非小细胞肺癌的疗效观察

目的 观察吉他西宾单药治疗老年晚期非小细胞肺癌（NSCLC）的疗效和毒性反应。方法 对36例Ⅲ～Ⅳ期NSCLC患者采用国产吉西他宾（泽菲）1250mg/m2,静脉注射30min,第1、8天,3～4周重复,2个周期后评价疗效。结果 36例均可评价疗效。总有效率（CR＋PR）为30.6%（11/36）,受益反应63.9%（23/36）,中位生存期6.6个月,1年生存率为27.8%,毒副反应以白细胞和血小板下降为常见,但均可耐受。结论 吉西他宾单药治疗老年晚NSCLC有较好疗效,可明显改善患者生存质量,延长生存时间,毒性反应轻,患者易于耐受。     

参芪扶正注射液配合吉西他滨治疗老年晚期非小细胞肺癌的临床观察

目的 观察参芪扶正注射液配合吉西他滨化疗在老年晚期非小细胞肺癌治疗中的作用.方法 将93例老年晚期非小细胞肺癌随机分为治疗组和对照组,其中治疗组47例,对照组46例.治疗组应用参芪扶正注射液静脉滴注配合吉西他滨每周方案化疗,化疗前3 d用参芪扶正注射液250 mL,静脉滴注,1次/d,7 d为1个周期;吉西他滨1.0 g/m2,d1,8,静脉注射,21 d为1个周期.对照组仅给予吉西他滨化疗,方案同治疗组.治疗后评价疗效和毒副反应.结果 两组疗效相近(P＞0.05),治疗组临床受益反应(CBR)高于对照组(P＜0.05).治疗组主要毒副反应发生率低于对照组(P＜0.05).结论 参芪扶正注射液配合吉西他滨化疗治疗老年晚期非小细胞肺癌能减轻化疗的毒副反应,提高CBR评价,改善患者生活质量.     

28例吉非替尼一线治疗老年非小细胞肺癌的临床经验

目的：探讨吉非替尼一线治疗晚期老年非小细胞肺癌（NSCLC ）的疗效和安全性。方法：分析2005年6 月～2008年9月在南方医院肿瘤中心接受吉非替尼（250mg/d ）做为一线治疗的老年晚期NSCLC 患者28例,主要分析中位生存期（OS）、无进展生存期（PFS）、客观有效率及毒副反应。结果：全组客观有效率：无CR,PR10例（35.7%）,SD14例（50.0%）。 中位PFS 为6.5 个月（95% CI3.9～9.0 个月）,1 年生存率为57.1%（16例）,中位OS为12.8 个月（95% CI6.3～19.3 个月）。 毒副反应较轻,大多为1～2级,3 级皮疹2 例,3 级腹泻1 例,经对症治疗后症状缓解,不影响治疗。结论：吉非替尼一线治疗老年非小细胞肺癌具有较好的疗效,且耐受性良好。     

The role of imaging in screening,diagnosis and staging of Non-Small Cell Lung Cancer (NSCLC)

Imaging plays a vital role in the management of NSCLC including diagnosis, staging and follow up. Computerised tomography (CT) is of value not only in the diagnosis of lung cancer, but also for screening and guiding intervention. CT and magnetic resonance imaging (MRI) are used in staging and provide anatomical information but have well known limitations in differentiating reactive from malignant nodes, fibrosis from active disease and in defining the extent of invasion. MRI, with its superior soft tissue contrast provides optimal information on brachial plexus and central nervous system involvement. Functional imaging using 2-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) is increasingly being used to provide unique information and when combined with anatomic imaging will provide better staging information for both local disease and the extent of metastases. FDG-PET or ^99mTc-depreotide may help in deciding which lesions need further investigation and the most appropriate lesion to biopsy. Multidetector CT is being used to detect lung cancer at an early stage when it is potentially curable by surgery although many problems exist, particularly the high false positive rates requiring further investigation, which will have implications on cost effectiveness for lung cancer screening programs.     

The Frequency of Epidermal Growth Factor Receptor (EGFR) mutations in Iraqi patients with Non-Small Cell Lung Cancer (NSCLC)

Objective: Non-Small Cell Lung Cancer (NSCLC) Carcinogenesis could be caused by numerous genetic mutations, one of the most common is the mutation in the Epidermal Growth Factor Receptor (EGFR) which was used in the advanced stages of the disease as a therapeutic goal. This study aims to estimate the frequency of Epidermal Growth Factor Receptor mutations in Iraqi patients with Non-Small Cell Lung Cancer. Methods: One hundred thirty-eight patients confirmed with NSCLC have participated in this study, patients were sent for EGFR testing by different oncology centers in Iraq. Data and samples were collected. The Mutation was detected using COBAS® DNA Sample Preparation Kit that designed to detect the following mutations: Exon 19: deletions and complex mutations; Exon 21: L861Q and L858R; Exon 18 mutation: G719X (G719A, G719C, and G719S); Exon 20: S768I, T790M, and insertions, this kit utilizes the technology of the real time Polymerase Chain Reaction. Results: This study was included 79 males and 59 females, with a mean age of 60.1±12.4 years. A positive EGFR mutations were found in 38 (27.53%) of samples. Exon 19 deletions (25/38, 65.8%) and substitution L858R in exon 21 10/38 (26.3%) were the most common mutations. Multiple mutations (Exon 20 and 19 combined together) were founded in 2/38 (5.3%), and 1/38 (2.6%) ALK mutation. Non-significant differences among age groups and gender in the incidence of mutations were found. Conclusion: The current study represents the first epidemiological study in Iraq to find EGFR mutations frequency among NSCLC patients that reveals the incidence rate of 27.53%, which is between the higher prevalence rate in Asian populations and lower rates in western countries. These results explain the genetic differences of NSCLC in the world due to ethnic differences of the population, more studies are needed in Arab countries to study the EGFR mutations, find the effect of ethnicity and environmental factors for lung cancer, and the subsequent therapy.