非小细胞肺癌的分子靶向治疗

与传统细胞毒性化疗相比,分子靶向治疗能更特异性作用于肿瘤而毒性反应较轻。新的靶向治疗药物得到发展,并相继在晚期非小细胞肺癌一线、二线治疗中进行临床试验,其中有的药物显示了较好的疗效。本文对近年来关于非小细胞肺癌靶向治疗的临床试验进行回顾。     

非小细胞肺癌的分子靶向治疗研究进展

肺癌是全球最常见的几种恶性肿瘤之一.近年来, EGFR、EML4-ALK、K-Ras、BRAF、C-MET、PIK3CA等越来越多的癌驱动基因被发现,以EGFR-TKIs为代表的靶向药为肺癌临床治疗带来新进展,但是大部分患者经靶向治疗后都会产生耐药,疗效仍不能满意.因此,基于肺癌基因驱动的机制探索及多靶点联合治疗是未来研究的方向.     

Gefitinib靶向治疗非小细胞肺癌的现状与展望

Gefitinib是一个选择性EGFR酪氨酸激酶抑制剂,凭其独特的作用机制和较轻的毒性反应而成为非小细胞肺癌(NSCLC)靶向治疗的热点之一.本文对gefitinib的作用机制、临床前研究、临床研究、不良反应和疗效预测因子等进行回顾.更深入的研究有助于准确评价gefitinib在NSCLC治疗中的地位.     

晚期非小细胞肺癌的治疗选择

肺癌是世界范围内癌症相关死亡的首要病因。近年来,非小细胞肺癌（non-small cell lung cancer ,NSCLC ）的治疗取得了巨大进步。人们对肺癌病理组织学认识不断深入,根据病理组织分型制订了相应的化疗方案。此外随着对分子生物学研究的发展,人们发现了在肿瘤发生发展过程中的驱动性基因突变,并以此研发了一系列针对不同分子亚型的靶向药物。本文将结合近期一系列临床研究结果,对晚期NSCLC 的临床治疗策略进行论述。     

现行晚期非小细胞肺癌治疗策略

肿瘤分子标志物的应用对肺癌化疗药物的选择及预测治疗效果有重要意义。对于具有良好行为状态(performance status,PS)评分的患者,以铂类为基础的双药联合治疗方案可延长生存期、改善生活质量、减少肿瘤相关症状。对于PS评分差的或高龄患者推荐单药化疗。二线治疗的选择包括:多西他赛、培美曲塞、吉非替尼和厄洛替尼。其中,培美曲塞对于非鳞癌患者可获益,吉非替尼则应用于EGFR突变患者。尽管治疗方法和可选择的药物不断发展,晚期非小细胞肺癌患者生存期仍有限,新的治疗方法和临床研究都有待进一步探索。     

现行晚期非小细胞肺癌治疗策略

肿瘤分子标志物的应用对肺癌化疗药物的选择及预测治疗效果有重要意义。对于具有良好行为状态（performance status,PS）评分的患者,以铂类为基础的双药联合治疗方案可延长生存期、改善生活质量、减少肿瘤相关症状。对于PS评分差的或高龄患者推荐单药化疗。二线治疗的选择包括：多西他赛、培美曲塞、吉非替尼和厄洛替尼。其中,培美曲塞对于非鳞癌患者可获益,吉非替尼则应用于EGFR突变患者。尽管治疗方法和可选择的药物不断发展,晚期非小细胞肺癌患者生存期仍有限,新的治疗方法和临床研究都有待进一步探索。     

非小细胞肺癌新辅助靶向及免疫治疗研究进展和展望

肺癌是全球发病率和死亡率最高的恶性肿瘤。近年来,随着新型药物的出现和治疗模式的优化,肺癌患者的预后已有一定改善。新辅助治疗是指对潜在可接受手术切除的患者,先给予术前抗肿瘤治疗后再行手术治疗。新辅助治疗通过术前治疗可以缩小肿瘤体积,降低肿瘤分期;并且可以杀灭患者机体中循环肿瘤细胞及微转移病灶,令患者远期生存获益。靶向治疗及免疫治疗已被应用于晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线治疗。因此,有临床试验尝试将以上两种治疗手段应用于早期可切除NSCLC患者的新辅助治疗。本文针对新辅助靶向及免疫治疗对早期可切除NSCLC患者的疗效、治疗中的潜在风险予以综述,并探讨新辅助治疗的未来发展方向。     

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. Conclusions: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.     

EML4-ALK fusion gene in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4-ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4-ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4-ALK and its association with NSCLC.     

局部晚期NSCLC放疗联合分子靶向治疗的研究进展

对于不能手术切除的局部晚期NSCLC,单纯放疗或放化疗是主要治疗手段,但总体疗效并不理想。近些年来,分子靶向治疗使局部晚期肺癌的治疗有了突破性进展,其中EGFR抑制剂和VEGF抑制剂的应用较为广泛。目前,对于局部晚期NSCLC越来越多的研究侧重于放疗联合分子靶向治疗方面,现有的Ⅰ-Ⅲ期临床研究显示,放疗联合分子靶向这种新治疗模式能否与同步放化疗、序贯放化疗和单纯放疗这三种目前现有的治疗模式相比,有待进一步探究。本文针对局部晚期的NSCLC放疗联合靶向治疗进行系统性的分析。     

放疗及同步EP方案化疗治疗不能手术切除非小细胞肺癌的疗效分析

60例非小细胞肺癌 (non smallcelllungcancer ,NSCLC)随机数字表法分为 2组 ,A组为常规放疗 +同步化疗组( 3 0例 ) ,B组为单纯放疗组 ( 3 0例 )。A组采用直线加速器 8MeVX线 ,DT66～ 76Gy/ 3 3～ 3 8F ;Vp 1610 0mg ,静脉滴入 ,d1～d5;DDP 40mg静脉滴入 ,d1～d3 ;化疗 3周重复 1次 ,共进行 3次。B组仅做常规放疗 ,方法、剂量、时间同A组。结果 :A组CR 8例 ,PR 17例 ,总有效率为 (CR +PR) 83 3 % ( 2 5 / 3 0 ) ,B组CR 5例 ,PR 11例 ,总有效率为 5 3 3 %( 16/ 3 0 )。两组差异有统计学意义 ,P <0 0 5 ;不良反应两组差异无统计学意义 ,P >0 0 5。     

早期非小细胞肺癌预后相关因素分析

早期非小细胞肺癌患者首选手术治疗后，仍有部分出现了局部复发和／或远处转移。筛选出预后差的患者辅以综合治疗显得尤为重要。本文分析了近年来研究的一些早期非小细胞肺癌的预后因素。     

High-dose thoracic radiation therapy at 3.0 Gy/fraction in inoperable stage I/II non-small cell lung cancer

OBJECTIVE: High-dose thoracic radiation therapy (HDTRT) alone has been an alternative to surgery in stage I/II non-small cell lung cancer patients with medical co-morbidities and/or poor performance status. Here, we report on the outcome and safety of HDTRT at 3.0 Gy per fraction for reduced treatment duration. METHODS: HDTRT alone at 3.0 Gy per fraction was given to 35 patients (22 at stage I and 13 at stage II). The median age was 73 years old and 14 patients had ECOG performance above 2. The median radiation dose to the primary lesion was 60 (54-66) Gy over 27 (23-38) days, and the dose to the mediastinum was individualized. RESULTS: After the median follow-up of 24 (3-72) months, local in-field progression developed in 11 patients (31.4%) and distant metastases in 14 (40.0%). The median survival period and the 3- and 5-year overall survival (OS) rates for all patients were 24.0 (95% CI: 13.57-34.43) months, 31.4 and 11.2%. Intercurrent deaths were observed in 11 patients. Treatment-related acute and subacute morbidities were observed in 20 patients (57.1%); however, there was neither treatment interruption nor long-term morbidity. CONCLUSIONS: On the basis of the above observations, we achieved treatment outcomes comparable with those of conventional protracted fractionation schedules at considerably shorter duration and lower cost by HDTRT at 3.0 Gy per fraction.     

吉非替尼治疗化疗失败晚期非小细胞肺癌的临床观察

目的：探讨吉非替尼（gefitinib）治疗化疗失败的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的疗效和毒性反应。方法：收集2005年6月至2009年8月期间我科收治的64例晚期 NSCLC患者,接受吉非替尼治疗,250 mg每天顿服,直至病情进展或因不良反应而终止治疗,观察患者的临床疗效和不良反应。结果：64例晚期NSCLC患者中,无1例CR,PR 22例,SD 23例,PD 19例,全组有效率（CR+PR）为34.38％,疾病稳定率为35.94％,疾病控制率（CR+PR+SD）为70.31％。中位生存期为5.9个月,截止随访时间35.94％（23/64）的患者仍存活。吉非替尼的疗效与性别及吸烟史相关（P＜005）,女性疗效优于男性（P<0.05）,无吸烟史优于有吸烟史。最常见的药物不良反应主要表现为Ⅰ、Ⅱ度皮疹（32.81％、26.57％）、腹泻（12.5％）。结论：对于化疗失败的晚期 NSCLC,吉非替尼能较好地缓解女性、腺癌、未吸烟患者的疾病相关症状,是一种安全、有效并具有较好耐受性的药物。     

非小细胞肺癌靶向治疗的耐药特点及应对策略

分子靶向治疗在驱动基因阳性的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者中已经获得显著的疗效,但靶向治疗后期发生的耐药问题也成为了非小细胞肺癌进一步治疗的难题。现有分子靶向治疗中已知多种肿瘤驱动基因靶点,常见的有EGFR、ALK、ROS1、HER-2、BRAF、MET等。本文将对上述基因突变靶点抑制剂的耐药特点及耐药后的进一步治疗进行综述。     

晚期非小细胞肺癌患者使用EGFR-TKI治疗后长期生存的研究

目的 探索应用表皮生长因子受体酪氨酸激酶抑制剂( EGFR-TKI)治疗晚期非小细胞肺癌(NSCLC)患者长期生存的影响因素,并研究长期生存者与EGFR突变关系.方法回顾性分析2002年12月至2007年6月在北京协和医院进行EGFR-TKI治疗的292例晚期NSCLC,并收集长期生存(定义为使用吉非替尼或厄洛替尼治疗...     

Prognosis of segmentectomy in the treatment of stage IA non-small cell lung cancer

With improvements in detection technology, increasing numbers of patients with non-small cell lung cancer (NSCLC) are being diagnosed at an early stage. In order to treat the illness with minimal invasion and preserve lung function to the greatest possible extent, there has been an increasing tendency towards treating early-stage NSCLC by segmentectomy. However, questions remain regarding whether patients may benefit from this procedure considering the surgical and oncological outcomes. Whether adequate margin distance and lymph node dissection may be achieved is one of the most important issues associated with this procedure. The present study reviews the prognosis of segmentectomy in the treatment of stage IA NSCLC.     

Second-line chemotherapy for non-small cell lung cancer

Several agents have been evaluated for the second-line treatment of patients with non-small cell lung cancer. The TAX 317 trial found that patients treated with docetaxel (Taxotere^®) 75 mg/m² had significantly longer survival than those treated with best supportive care alone. In addition, symptom control was better for patients who received chemotherapy. The TAX 320 trial found that treatment with docetaxel 75or 100 mg/m²resulted in significantly higher response rates than treatment with vinorelbine (Navelbine^®) or ifosfamide (Mitoxana^®), and the 1-year survival rate was also significantly better for patients treated with docetaxel 75 mg/m². A large randomized trial compared pemetrexed (LY-231514 or Alimta^®) 500 mg/m² with docetaxel 75 mg/m². Response and survival rates were similar in the two treatment arms, however, the toxicity profile of pemetrexed was superior to that of docetaxel with significantly less Grade 3/4 neutropenia and febrile neutropenia. Fewer patients in the pemetrexed arm required hospitalization. Topotecan (Hycamtin^®) 2.3 mg/m²/day orally for 5 days has been compared with docetaxel 75 mg/m²in a large 800-patient study. The results of this trial are awaited. Gemcitabine (Gemzar^®) and irinotecan (Campto^®) have been evaluated both as single agents and in combination with each other and study results do not suggest that either of these drugs is superior to docetaxel or pemetrexed. The vinca alkaloid vinorelbine has proved to be inferior to docetaxel in a randomized trial. The epidermal growth factor receptor inhibitors gefitinib (ZD1839, Iressa^®) and erlotinib (CP-358774, OSI 774, Tarceva^®) have been evaluated in Phase II trials in the second- and third-line setting. Both drugs have demonstrated interesting response rates ranging from 10 to almost 20%. The results of placebo-controlled randomized trials of this family of drugs are awaited. In summary, several studies have now found a definite role for the second-line treatment of patients with non-small cell lung cancer.     

The role of radiation therapy for stage IIIB non-small cell lung cancer: Impact of clinical nodal stage on survival

Background From 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital. Methods All patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation. Results The actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage NO-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months;P<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0–1 and those with a status of 2–3 (P=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years. Conclusion These results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage.     

培美曲塞治疗非小细胞肺癌

培美曲塞是一种多靶点的新型叶酸代谢拮抗剂,它通过抑制胸苷酸合成酶、二氢叶酸还原酶和甘氨酰胺核苷酸甲酰转移酶破坏细胞内叶酸依赖性代谢过程干扰细胞复制,从而抑制肿瘤生长。目前有关培美曲塞治疗包括恶性胸膜间皮细胞瘤、非小细胞肺癌、乳腺癌、胰腺癌、胃肠道肿瘤、头颈部肿瘤等多种恶性肿瘤的临床研究均有报道,本文综述培美曲塞单药或多药联合治疗在非小细胞肺癌的临床研究。