Small cell lung cancer

Lung cancer is the most common cause of cancer death in the United States, with approximately 135,000 men and women dying each year. While much has been learned about the etiologic risk factors, less progress has been made in therapy. Five-year survival rates remain at less than 10%. However, there has been some progress in the therapy of one histological subtype of lung cancer, small cell lung cancer. Totaling around 20% of lung cancer cases, small cell lung cancer is distinct from the other histologic subtypes in its biologic behavior and responsiveness to therapy. In the 1960s, the median survival for patients with small cell lung cancer was approximately 3 months. With combination chemotherapy and radiotherapy median survivals now range from 1 to 2 years, and there is evidence for a curative potential since approximately 10% of patients who initially present with limited disease survive greater than 2 years. The unique clinical aspects of this histological subtype potentially relate to its underlying cell of origin. This behavior is reflected in the numerous paraneoplastic syndromes that frequently accompany small cell lung cancer. Its propensity for early dissemination have made staging the extent of disease an important part of the clinical evaluation. Since small cell lung cancer is sensitive to both chemotherapy and radiation therapy, there have been multiple clinical trials evaluating drug/radiotherapy combinations. This article will briefly describe the unique aspects of small cell lung cancer as opposed to other histological subtypes of lung cancer and give an overview of the current clinical approach and treatment of this disease.     

112例小细胞肺癌患者多因素生存分析

目的 分析小细胞肺癌患者顸后的影响因素.方法 收集112例经组织病理学或细胞学明确的小细胞肺癌患者临床资料,分析性别、年龄、分期、血红蛋白水平、乳酸脱氢酶水平、一线化疗疗效、放疗及手术治疗等因素与患者生存期的关系,采用Kaplan-Meier法生存分析,进行Log-rank非参数检验,用COX比例风险模型进行多因素生存分析.结果 全组患者1、2、3年生存率分别为71.4%、38.4%和14.3%,其中局限期1、2、3年生存率分别为80.0%、47.1%和17.1%,广泛期1、2、3年生存率分别为57.1%、23.8%和9.5%.全组中位生存时间为22个月,其中局限期生存时间24个月,广泛期生存时间16个月.单因素分析发现分期、血红蛋白水平、乳酸脱氢酶水平、一线化疗疗效、放疗及手术治疗均可影响患者的生存期.多因素分析则提示分期、一线化疗疗效、放疗及手术治疗是患者生存的独立影响因素,其相对危险度分别为0.687、0.635、0.412、0.203.结论分期、化疗疗效、是否接受放疗及手术治疗可能是影响小细胞肺癌患者预后的主要因素.     

Small cell carcinoma of the lung: results of combination chemotherapy and radiation therapy

A retrospective study of 244 patients treated for small cell carcinoma of the lung from Jan 1, 1971 to Dec 31, 1976 revealed that 34% of patients, with local-regional disease who received radiation alone survived one year (median survival, seven months), and 53% with local-regional disease survived one year (median survival, 12 months) when treated with combination chemotherapy and radiation. The one-year survival for patients presenting with metastatic disease was 14.5% (median survival, five months) when treated with radiation alone and 50% (median survival, 11 months) when treated with combination chemotherapy and radiation. Although combination chemotherapy and radiation will prlong the disease-free interval in patients with small cell carcinoma of the lung, more than 90% will develop evidence of progressive disease within two years.     

Eribulin mesylate (E7389): review of efficacy and tolerability in breast, pancreatic, head and neck, and non-small cell lung cancer

BackgroundEribulin mesylate is a halichondrin B analogue that acts as a nontaxane microtubule dynamics inhibitor. Eribulin was approved in the United States in 2010 for the treatment of metastatic breast cancer for patients who have received at least 2 metastatic breast cancer chemotherapeutic regimens, including an anthracycline and a taxane. Eribulin is administered as a single agent at 1.4 mg/m² IV for 2 to 5 minutes on days 1 and 8 of a 21-day cycle.ObjectivesThe goals of this article are to review eribulin's medication profile, including pharmacology, pharmacokinetic properties, efficacy, and tolerability. Recommendations are provided at the end of the article based on the published information.MethodsPubMed, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov were searched from the beginning of each database through January 3, 2012, for relevant articles on human studies published in English. Search terms included eribulin, eribulin mesylate, and Halaven. Clinical trials, case reports, comparative studies, meta-analyses, evaluation studies, controlled clinical trials, and randomized controlled trials were included as search limits. The references from selected articles were also reviewed to identify additional publications. Eisai, the manufacturer of eribulin mesylate, was also contacted for information regarding trials listed in Clinicaltrials.gov but not yet published.ResultsOne Phase III trial was identified that evaluated eribulin for use in patients with metastatic breast cancer. Four Phase II trials were identified that studied eribulin in patients with head and neck, pancreatic, and non–small cell lung cancers. The median overall survival among previously treated metastatic breast cancer patients treated with eribulin was 13.1 months compared with 10.6 months (P = 0.041) with other active chemotherapy for this setting. In non–small cell lung cancer, median overall survival in eribulin-treated patients has been reported as 9.4 months in an unselected population and varies according to taxane sensitivity: 12.6 months in taxane-sensitive disease versus 8.9 months in taxane-resistant disease. Patients with head and neck or pancreatic cancers did not experience improvements in response rates or survival outcomes when treated with eribulin in clinical trials.ConclusionsEribulin is approved by the Food and Drug Administration for patients with previously treated metastatic breast cancer and has demonstrated a survival benefit compared with standard treatment options in this setting. Non–small cell lung cancer patients had improved response rates when treated with eribulin in open-label, nonrandomized, Phase II trials reported in abstract form. Eribulin was not effective in the treatment of head and neck or pancreatic cancer in Phase II trials.     

肝转移出现的时段对非小细胞肺癌预后的影响

目的：探讨肝脏转移出现的时段对非小细胞肺癌患者生存的影响。方法：选择1999-01/2006-09在我院死亡的非小细胞肺癌238例,回顾分析肝转移出现时间对预后的影响。结果：肺癌患者初诊时出现肝转移20例,中位生存期7（5,9）个月;初次诊断无肝转移253例,中位生存期13（12,14）个月,差异显著（P=0.008 5）。而总患病期间出现肝转移以及首发肝转移对预后影响不显著。结论：初诊时出现肝脏转移是非小细胞肺癌患者显著影响预后的因素。     

一例广泛期小细胞肺癌的循证治疗

目的针对一例广泛期小细胞肺癌合并恶性胸水、肝转移的治疗问题,检索当前最佳临床证据,为患者恶性胸水的对症治疗和后续化疗方案提供依据。方法根据循证临床实践的PICO原则,提出问题,检索证据,对所获证据进行质量评价,并结合患者意愿制定治疗方案。结果共纳入10个随机对照试验,13个系统评价／Meta分析和3篇临床指南。证据结果表明：化疗能提高广泛期小细胞肺癌患者的生存率,艾迪注射液可以减轻放化疗所致的不良反应,提高患者的生存质量。EP方案是小细胞肺癌化疗最主要的标准化疗方案。结合患者情况,我们采用胸腔闭式引流术加经胸膜腔内注入博来霉素,待患者病情好转后,采用EP方案化疗,患者生存期要比广泛期小细胞肺癌的平均存活期长,生活质量得以提高,家属对治疗满意。结论广泛期小细胞肺癌患者以化疗为主,同时辅以对症、支持治疗,预防性头颅照射（PCI）可以减少脑转移的发生并提高患者生存率。     

盐酸安罗替尼治疗晚期非小细胞肺癌的临床观察

目的:探讨盐酸安罗替尼治疗晚期非小细胞肺癌(non-small lung cancer,NSCLC)的临床疗效及不良反应。方法:回顾性分析2017年6月至2019年1月徐州医科大学附属医院收治的三线治疗及以上的晚期NSCLC,应用盐酸安罗替尼治疗的45例患者的临床资料,综合评价患者的疗效和无进展生存期(progression-free survival,PFS)以及不良反应情况。结果:共纳入45例患者,将患者分为安罗替尼单药组(24例)与安罗替尼联合用药组(21例),其中联合白蛋白结合型紫杉醇化疗17例,联合纳武单抗免疫治疗4例。在45例患者中,部分缓解(partial remission,PR)占4.4%(2/45),疾病稳定(stable disease,SD)占88.9%(40/45),疾病进展(progressive disease,PD)占6.7%(3/45),客观有效率(objective response rate,ORR)为4.4%,疾病控制率(disease control rate,DCR)为93.3%。45例患者的中位PFS为3.70个月,经log-rank检验结果显示不同治疗方案差异有统计学意义(P<0.05)。其中单药组患者中位PFS为3.30个月,联合用药组患者中位PFS为5.30个月,联合用药组PFS优于单药组。不良反应主要包括乏力、高血压、食欲不振、手足综合征等,其中3级不良事件包括高血压、手足综合征及骨髓抑制,未发现4级及以上的不良事件。结论:盐酸安罗替尼在三线治疗及以上的晚期NSCLC的治疗中,具有较好的疾病控制及生存获益,且不良反应相对可控。     

卡铂、表阿霉素为主联合动脉灌注对肺癌的近期疗效观察

目的：探讨卡铂、表阿霉素在动脉中联合灌注治疗肺癌中的近期疗效分析。方法：46例中晚期肺癌术前均经病理诊断证实。鳞癌26例,腺癌13例,未分化小细胞肺癌7例,采用经皮股动脉穿刺插管,选择患侧支气管动脉开口处,进行动脉造影确诊后,再进行大剂量抗癌药物灌注及栓塞,间隔1个月后重复治疗一次,结果：按实体癌的疗效标准,动脉联合灌注治疗后,磷癌CR6例,PR24例,NR2例,腺癌CR2例,PR16例,NR2例,未分化小细胞癌CR1例,PR2例,NR1例,本组46例病人随访3年,生存期6个月以上5例,6－12个月16例,12－20个月15例,21－24个月8例,25－36个月7例,平均生存期为14．2个月。结论：支气管动脉联合大剂量灌注化疗药物,优于单纯动脉灌注效果,本文CBP加入Vp-16临床实验对小细胞肺癌有效率的89．2％,即可提高临床治疗效果,同时又能达到治疗目的。     

Complete response of esophageal small cell carcinoma amrubicin treatment

Small cell carcinoma of the esophagus (SmCCE) is a rare and aggressive disease known to have a poor prognosis. SmCCE patients are generally treated with a chemotherapeutic regimen for small cell lung cancer. Salvage therapy for patients with relapsed or refractory tumors has not yet been established. A 63-year-old man with extensive SmCCE was treated with chemotherapy consisting of cisplatin (CDDP) and irinotecan (CPT-11). After the second course of CPT-11/CDDP, the celiac lymph node increased in size. Amrubicin (AMR) as second-line chemotherapy was started. The patient had a complete response after the fifth course of AMR, resulting in an 8-month progression-free survival after initial administration. This case suggests that, as in small cell lung cancer, AMR is effective for SmCCE.     

Treatment of small cell carcinoma of the lung with methotrexate, doxorubicin, cyclophosphamide, and lomustine: a community-based study

Forty-four patients with undifferentiated small cell carcinoma of the lung (SCCL) were diagnosed and treated at community hospitals. Patients with limited disease were treated with surgical resection or primary radiation therapy (RT) followed by chemotherapy; those with extensive disease received chemotherapy followed by RT if there was not a complete primary response. The chemotherapy used was a combination of methotrexate, doxorubicin, cyclophosphamide, and lomustine. Median survival for patients with both limited and extensive disease was 12 months, with a six-month survival of 89%. Half of the patients had recurrence in the lung. The toxicity was moderate and tolerable. We conclude that this combination chemotherapy plus radiation therapy carries acceptable toxicity and can be used in a community hospital to achieve response rates and survival of SCCL equivalent to that obtained in large cancer centers.     

Limited stage small cell lung cancer: analysis of clinical prognostic factors

In an attempt to identify clinical features of prognostic value in patients with limited stage small cell lung cancer, we retrospectively reviewed the records and chest roentgenograms of 101 such patients seen at Vanderbilt University Hospital. All patients were treated with combination chemotherapy regimens of comparable efficacy with or without chest radiotherapy and/or surgical resection. Median survival for the 101 patients was 16 months; the three-year actuarial survival was 14%. Elevated serum LDH level at the time of diagnosis was predictive of improved survival by both univariate and multivariate analyses (P less than .01). Initial tumor volume (calculated from tumor measurements) on chest roentgenogram and clinical TNM stage were unrelated to survival. Until the prognostic significance of an elevated serum LDH level is confirmed by other investigators, we cannot recommend any modification in the current system for staging small cell lung cancer. Although patients with limited stage small cell lung cancer form a clinically heterogeneous group, they should continue to be treated uniformly.     

Current perspectives of new agents in lung cancer

Irinotecan(CPT-11), Taxol, Taxotere, vinorelbine and gemcitabine have shown a significant activity in previously untreated non-small cell lung cancer (NSCLC). Cisplatin(CDDP) combined with vinorelbine, gemcitabine or tirapazamine was significantly superior in survival to CDDP alone in the treatment of advanced NSCLC. Patients with NSCLC treated with combination of CDDP and Taxol or vinorelbine lived longer than those treated with conventional CDDP-based chemotherapy. CPT-11, topotecan, taxol and amrubicin have demonstrated to be active against small cell lung cancer(SCLC). Combination of CPT-11 and CDDP have had a higher response rate, and better median survival(13 months) in patients with extensive disease SCLC. Clinical trials of target-based drugs including matrix metalloprotenase inhibitors, anti-angiogenesis, tyrosine kinase inhibitors, farnesyl transferase inhibitors and monoclonal antibodies have been initiated in solid tumors including lung cancer. Development of new anti-cancer agents is essential to improve outcomes of patients with lung cancer.     

Improving outcomes in lung cancer patients

Lung cancer is the leading cause of cancer mortality in the UK resulting in more than 33,500 deaths in 2008, 4,000 more than for bowel and breast cancer combined. Five-year survival figures are poor but have recently improved from around 5% to 7.5% in men and 8.5% in women. The key recommendations in the updated NICE guideline seek to ensure that: all multidisciplinary teams apply efficient methods to diagnose and stage patients accurately; fitness assessment is an objective process; as many patients as possible are offered treatment with curative intent; those with small cell lung cancer are offered the most effective treatment; and patients are referred early for endobronchial treatment. There are potentially more important and difficult challenges for primary and integrated care. Almost three quarters of patients with lung cancer have advanced disease atpresentation, and many of these have had symptoms for many months. Early diagnosis, awareness of warning symptoms and prompt referral are therefore major priorities. If we are to improve outcomes in lung cancer, more patients need to be sent for chest X-ray and referred urgently. If the chest X-ray is normal but there is a high suspicion of lung cancer the patient should still be referred urgently. To ensure that all patients have the best chance of being offered curative treatment, patients should be re-assessed by the surgeon and/or radiation oncologist after any optimisation. Patients should be encouraged to stop smoking, as this reduces postoperative complications, but surgery should not be postponed. Surgery that minimises loss of lung tissue is recommended. The latest radiotherapy techniques, such as stereotactic body radiotherapy, that minimise dose to normal lung are encouraged.     

多西他赛联合奥沙利铂化疗对晚期非小细胞肺癌的临床疗效

目的 探讨多西他赛联合奥沙利铂治疗晚期非小细胞肺癌化疗的临床疗效。方法 选取住院治疗的 118例晚期非小细胞肺癌患者,采用随机数字法分为观察组和对照组各59例,对照组患者行顺铂联合多西他赛治疗, 观察组患者行奥沙利铂联合多西他赛治疗,比较两组患者实体肿瘤疗效差异、疾病无进展生存时间、总体生存时间以 及不良反应发生率等疗效指标差异。结果 观察组患者完全缓解、部分缓解以及临床有效率依次为11.9%(7/59)、 47.5%(28/59)、59.3%(35/59),对照组为8.5%(5/59)、39.0%(23/59)、47.5%(28/59),差异无统计学意义(P > 0.05)。观察组患者疾病无进展生存时间、总体生存时间依次(12.17±0.98)月、(20.07±2.38)月,均明显长于对照组 的(8.48±0.68)月、(16.07±2.78)月(P <0.05),观察组患者骨髓抑制、消化道异常、白细胞下降、外周神经毒性、肝 功能异常等不良反应发生率均明显低于对照组,且程度明显轻于对照组,差异均具有统计学意义(P <0.05)。结论 多西他赛联合奥沙利铂治疗晚期非小细胞肺癌化疗的临床疗效明确,不良反应发生率较低,是治疗晚期非小细胞肺癌 的有效措施之一。     

吉非替尼联合西黄丸治疗晚期非小细胞肺癌的疗效评价

目的 评价吉非替尼联合西黄丸治疗晚期非小细胞肺癌的临床疗效.方法 选取2015年9月至2018年12月我院收治的晚期非小细胞肺癌患者21例为研究对象,所有患者均接受吉非替尼联合西黄丸治疗,观察患者的近期疗效.结果 21例患者中,疾病稳定(SD)10例,部分缓解(PR)8例,疾病进展(DP)3例,完全缓解(CR)0例,疾病缓解率(DRR)38.09％(8/21),疾病控制率(DCR)85.71％(18/21).用药治疗后随访6～24个月,36例患者中死亡3例,无进展生存期(PFS)5～14(7.12±0.93)个月,总生存期(OS)6～24(10.23±1.10)个月.用药期间,出现恶心、呕吐Ⅰ度1例(4.76％);AST/ALT水平升高Ⅱ度1例(4.76％);皮疹Ⅰ度4例(19.04％)、Ⅱ度1例(4.76％);腹泻Ⅰ度2例(9.52％).结论 吉非替尼联合西黄丸可以显著改善晚期非小细胞肺癌本身及与治疗有关的热证或热毒证的症状,提高生存质量,延长生存时间,减轻毒副作用的发生率及程度,值得推广应用.     

TKI药物对非小细胞肺腺癌的临床效果观察

目的：探讨T K I药物对非小细胞肺腺癌的临床治疗效果。方法选取非小细胞肺腺癌患者100例，分为两组，使其有可比性。对其临床资料进行回顾分析。观察组患者采取吉非替尼治疗，对照组除不使用吉非替尼外所有治疗均同观察组。对两组患者治疗前后肿瘤大小进行比较，对观察组患者的临床效果进行统计，并记录不良反应发生情况。结果经过治疗，两组患者肿瘤均缩小，其中观察组缩小更为明显。观察组患者随访40个月，死亡31例，中位生存期16．73个月；生存期超过1年者28例（56．00％），35例（70．00％）患者疾病进展或者出现死亡，中位无疾病进展时间12．63个月；16例（32．00％）患者达到部分缓解，中位缓解期11．37个月；20例（40．00％）患者稳定，10例（20．00％）患者进展，还有4例（8．00％）患者疗效未能作出评价。除4例疗效未能作出评价的患者外其余46例患者在接受吉非替尼治疗过程中，其临床疗效受患者年龄、是否吸烟、有无皮疹以及呼吸困难是否加重等因素影响。皮疹是吉非替尼治疗后最常见的不良反应，其次是腹泻，各种不良反应均以Ⅰ度为主，Ⅱ度和Ⅲ度很少。结论吉非替尼作为TKI的代表性药物，在治疗非小细胞肺腺癌方面有确切效果，可以延长患者的生存期，而且不良反应少，容易在临床进行推广。     

以手术治疗参与的综合治疗在Ⅱ~ⅢA期小细胞肺癌中的应用效果

目的比较以手术治疗参与的综合治疗、单纯放化疗对Ⅱ~ⅢA期小细胞肺癌患者的效果。方法回顾性分析我院2012年12月至2014年12月收治的50例小细胞肺癌患者的临床资料。根据治疗方式将50例患者分为观察组和对照组,每组25例。观察组采用以手术治疗参与的综合治疗,对照组采用单纯放化疗。比较两组患者的生存率。结果观察组患者的1、2、3及5年生存率分别为80.00%、60.00%、52.00%、32.00%,均高于对照组患者的52.00%、32.00%、24.00%、8.00%(P<0.05)。结论给予Ⅱ~ⅢA期小细胞肺癌患者以手术治疗参与的综合治疗,可以延长患者的生存时间,具有积极的临床价值。     

吉西他滨（Gemcitabine）联合铂类药物治疗老年中晚期非小细胞肺癌（NSCLC）的临床观察

目的：探讨吉西他滨(Gemcitabine)联合铂类药物治疗老年中晚期非小细胞肺癌(NS(NSCLC)的临床疗效和毒性。方法：予吉西他滨(Gemcitabine)1000mg/m^2第1、8天静滴并联合铂类药物治疗老年非小细胞肺癌(NSCLC)20例，三周为一治疗周期，两周期后评价疗效和毒副作用，随访缓解期和生存期。结果：本组20例病例中，治疗总有效40％，中位缓解期7个月，中位生存期9个月，主要毒副作用为骨髓抑制和胃肠道反应。其中白细胞减少发生率为80％，血小板减少发生率为60％。结论：吉两他滨(Gemcitabine)对老年非小细胞肺癌(NSCLC)有较好疗效，主要毒性反应为较严重的血液学毒性，老年患者最好辅以G-CSF或GM—CSF以及免疫与营养支持治疗，则能顺利完成化疗，吉西他滨(Gemcitabine)联合铂类药物可做为老年非小细胞肺癌(NSCLC)的一线治疗方案。     

三维适形放疗联合化疗治疗局限期小细胞肺癌的临床疗效

【目的】观察三维适行放疗（3DCRT）联合EP方案化疗治疗局限期小细胞肺癌的近期疗效和不良反应。【方法】应用3D-CRT技术联合EP方案化疗治疗局限期小细胞肺癌患者30例。3D-CRT计划系统制定放疗计划,处方剂量为45Gy,均采用超分割放疗,30次照射,1．5Gy／次,2次／日。【结果】肿瘤完全缓解17例（56．6％）,部分缓解8例（26．7％）,稳定5例（16．7％）,总有效率达83．3％,1年生存率73．3％,2年生存率43．3％。【结论】3D-CRT联合化疗治疗局限期小细胞肺癌有较好的疗效,毒性反应经对症处理后可以耐受。     

吉非替尼耐药的晚期非小细胞肺癌联合重组人血管内皮抑素解救治疗的临床研究

目的探讨晚期非小细胞肺癌(NSCLC)患者吉非替尼治疗失败后,联合恩度解救治疗的疗效和生存。方法确定为吉非替尼治疗失败的晚期NSCLC患者接受联合恩度治疗,具体用法:恩度15 mg/d,连续静脉输注1 d,休息7 d,21 d/周期。观察患者联合治疗的疗效,生存和毒性结果。结果 1例获得部分缓解(PR)(10%),6例稳定(SD)(60%),3例进展(PD)(30%);客观缓解率(ORR)为10%,疾病控制率(DCR)为70%;联合治疗后的中位PFS为4.2个月(95%CI:3.21个月~5.19个月);联合治疗开始后的中位OS是8个月(95%CI:4.96个月~11.04个月)。DCR、PFS和OS与患者的性别、年龄、PS评分、病理类型及易瑞沙服药时间长短均无相关性。结论吉非替尼治疗失败后联合恩度解救治疗可使部分患者疾病获得稳定,延长生存时间,并且毒性可以耐受,可以扩大样本量进行深入研究。