伊立替康在广泛期小细胞肺癌化疗中的应用

小细胞肺癌(small cell lung cancer, SCLC)的发生率占肺癌的15%～20%,具有恶性程度高、进展快等特点,联合化疗是其主要的治疗方法.依托泊甙联合铂类的2药方案是目前广泛期SCLC的标准治疗方案,尽管其缓解率较高,但中位生存时间仍较短.为了进一步提高SCLC的治疗效果,近年关于伊立替康等第3代新药的研究逐渐增多.这些研究的结果显示,在广泛期SCLC的一线治疗中伊立替康联合铂类的疗效优于或相当于依托泊甙联合铂类;伊立替康联合其他药物在复发或难治的SCLC中具有一定的疗效.     

2007年肺癌治疗新热点-来自ASCO的证据

 【摘要】　可手术切除非小细胞肺癌（NSCLC）术前化疗的价值尚未肯定，局部晚期NSCLC同期化放疗后巩固化疗仍需进一步验证。贝伐单抗与化疗联合应用一线治疗晚期NSCLC优于单用化疗，目前尚无证据显示吉非替尼二线治疗晚期NSCLC的总生存优于多西紫杉醇。细胞分子信号通路和药理基因组学的研究结果可能指导肺癌的个体化治疗。伊立替康与铂类联合一线治疗广泛期小细胞肺癌（SCLC）优于EP方案，所有化疗取得缓解的广泛期SCLC接受预防性脑放疗（PCI）可延长生存。     

2012年美国临床肿瘤学会年会小细胞肺癌研究进展

文章综述第48届美国临床肿瘤学会年会中关于小细胞肺癌(SCLC)的研究进展.同步放化疗是局限期SCLC患者的标准治疗,化疗方案推荐EP方案,从第3周期化疗开始放疗也可以作为其选择;在广泛期SCLC的化疗中氨柔比星联合顺铂(AP)方案劣于伊立替康联合顺铂(IP)方案,在足叶乙甙联合卡铂(EC)方案基础上加恩度未能提高生存期;拓扑替康联合阿柏西普在铂类经治的患者中值得进一步研究;循环肿瘤细胞数量下降与SCLC治疗有效相关,c-Met可作为SCLC的独立预后因子,女性是较好生存期的阳性预后因子;SCLC患者中存在较低的EGFR突变.     

复发或难治性小细胞肺癌的化疗进展

复发或难治的SCLC预后差,化疗对其缓解率低,中位生存时间为4个月[1].广泛期的.所有患者或局限期的大多数患者,肿瘤进展后需要二线化疗.对于复发的SCLC,仍有多种药物具有抗肿瘤活性,如紫杉类的紫杉醇(PTX)、泰索帝,拓扑异构酶Ⅰ的抑制剂拓扑替康(TPT)、伊立替康(CPT-11),异环磷酰胺、足叶乙苷(VP-16)、顺铂及卡铂等.复发或转移后的二线化疗尚无公认的统一标准治疗.目前应用较多的化疗方案包括:TPT单药化疗,TPT PDD,TPT IFO,TPT PTX等的联合化疗;CPT-11 IFO、CPT-11 PDD、CPT-11 CBP、CPT-11 PDD VP-16的联合化疗;PTX CBP、PTX IFO的联合化疗;国内应用HCPT代替TPT及CPT-11联合化疗等.含阿霉素的联合化疗,在铂类及VP-16失败后几乎无效.     

小细胞肺癌治疗回顾及展望

小细胞肺癌(small cell lung cancer,SCLC)是对放、化疗极为敏感的恶性实体肿瘤之一,依托泊苷联合铂类的方案仍然是广泛期小细胞肺癌的一线标准治疗方案,客观缓解率为50%～70%.联合放化疗可以使局限期小细胞肺癌完全缓解率增加到40%～50%,但大部分患者会复发.对于复发的患者,单药托泊替康化疗是到目前为止二线治疗较为合适的治疗药物.胸部联合放、化疗、对于放疗时间和分级的优化、预防性的脑放疗可使3年生存率明显提高.     

93例广泛期小细胞肺癌（SCLC）综合治疗的预后因素分析

目的:回顾性分析我院93例广泛期SCLC放化综合治疗的疗效,对影响小细胞肺癌预后的多个因素进行分析。方法:选取2008年10月-2010年10月,陕西省肿瘤医院放疗科收治的经病理学或细胞学证实的93例广泛期SCLC患者,患者均采用放化综合治疗。对比风险模型进行多因素分析。主要收集患者的年龄、性别、分期、PS评分、转移部位、胸部放疗情况、化疗周期、预防性脑放疗情况,观察中位生存时间、总生存时间。结果:93例患者的1年生存率39.8%,2年生存率11.8%,3年生存率2.18%,中位生存期11.56个月。单因素分析显示PS评分、胸部放疗、预防性脑放疗、化疗周期数、脑转移对患者的生存期有影响。多因素分析显示PS评分、预防性脑放疗、化疗周期数是预测广泛期小细胞肺癌预后的因素。结论:对于广泛期小细胞肺癌患者PS评分<2、化疗周期数≥4、预防性脑放疗均提示其预后较好。     

TP方案与EP方案治疗广泛期小细胞肺癌

广泛期小细胞肺癌(extensive small-cell lungcancer,ED-SCLC)约占小细胞肺癌的60%～70%,对放、化疗高度敏感,但治愈率低。拓扑替康(topote-can,TPT)是被美国FDA批准应用于治疗复发性小细胞肺癌的唯一有效单药。2001年7月～2004年12月,我们用拓扑替康联合顺铂的TP方案治疗广泛期小细胞肺癌,采用非随机分组方法和同期治疗的EP方案进行比较,观察两方案的疗效和耐受性。1资料与方法1·1一般资料33例均为经组织或细胞学确诊的SCLC,临床分期为广泛期(定义为:肿瘤超出一侧胸腔,包括对侧肺门、锁骨上或/及远处转移);既往未行放疗、化疗或手…     

小细胞肺癌治疗新进展

小细胞肺癌（small cell lung cancer，SCLC）治疗进展缓慢，依托泊苷联合铂类和拓扑替康作为SCLC一线和二线治疗选择已经延续30余年，三线及以上SCLC一直没有标准治疗方案。因此，迫切需要新的治疗方案提高SCLC治疗的效果。最近，免疫治疗、新型化疗药物以及小分子抗血管药物的发展，在SCLC领域实现了突破，为SCLC建立新的治疗标准。随着对SCLC分子机制的理解，SCLC分子分型初步建立，分型而治的策略开始了探索。本研究对SCLC治疗的最新进展进行综述。      

伊立替康联合铂类药物治疗广泛期SCLC的研究进展

小细胞肺癌(Small cell lung cancer,SCLC)在肺癌中约占10%~15%,是一种恶性程度较高的肿瘤,具有进展快且转移早的特点,联合化疗是广泛期SCLC主要的治疗方法。依托泊苷(Etoposide,VP-16)联合顺铂(Cisplatin,DDP)的方案(简称EP方案)是治疗广泛期小细胞肺癌(Extensive disease small cell lung cancer,ED-SCLC)的标准方案,这些年来并未取得突破性的治疗进展。伊立替康联合铂类抗肿瘤药物的方案在治疗ED-SCLC方面显示出有效性和安全性,本文就伊立替康联合铂类药物治疗ED-SCLC的现状做一简要综述。     

小细胞肺癌放射治疗新进展——东西方的探索

小细胞肺癌(SCLC)是我国肺癌常见类型之一,90年代后,SCLC的全身治疗方面没有令人兴奋的进展,但是放疗在SCLC中的应用研究取得了部分进展,为SCLC治疗疗效的提高提供了可能,这些进展主要包括广泛期SCLC的胸部放疗及脑预防照射、局限期SCLC胸部放疗剂量及放疗技术的研究、早期SCLC脑预防照射的价值研究等。笔者就其内容在东西方研究的进展加以综述,希望能带给读者一些帮助和借鉴。     

The Role of Integrated 18F-FDG PET-CT as a Staging Tool for Limited-Stage Small Cell Lung Cancer: A Retrospective Study

Background: The aim of this study was to evaluate whether positron emission tomography-computed tomography (PET-CT) could be used as part of the staging work-up in patients with limited-stage disease (LD) small cell lung cancer (SCLC). Patients and Methods: Between January 2002 and December 2007, a total of 73 patients with presumed LD on CT, who underwent a PET-CT scan, were included in this study. Results: Conventional work-up revealed distant metastases in 12 patients. Out of 61 patients diagnosed as LD SCLC, PET-CT found unexpected distant metastases in 15 (24.6%) patients (LD/extensive-stage disease (ED)) of whom 13 (21.3%) were upstaged as a consequence. In 10 (76.9%) of the 13 upstaged patients, treatment was changed. The median survival of LD/LD SCLC patients who underwent concurrent chemoradiotherapy and chemotherapy only was 21.9 and 17.5 months, respectively. The median survival of LD/ED and ED/ED SCLC patients who received chemotherapy only was 17.4 and 14.1 months, respectively. The median survival of LD/LD SCLC patients who received concurrent chemoradiotherapy was superior to that of LD/ ED and ED/ED patients who received chemotherapy only (p = 0.037 and 0.004, respectively). Conclusion: The addition of PET-CT seems to allow more accurate staging and may thus protect a percentage of SCLC patients from potentially futile and toxic radiotherapy.     

Treatment of small cell lung cancer in the elderly

Small cell lung cancer (SCLC) accounts for approximately 20% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. In limited disease, the median survival time is about 12-16 months, with a 4%-5% long-term survival rate; in extensive disease the median survival time is 7-11 months. More than 50% of lung cancer patients are diagnosed when they are over the age of 65, and about 30% are over 70. Elderly patients tolerate chemotherapy poorly compared with their younger counterparts, because of age-related progressive reductions in organ function and comorbidities. The standard therapy for limited disease is combined chemoradiotherapy, followed by prophylactic brain irradiation for patients achieving complete responses. In the elderly, the addition of radiotherapy to chemotherapy must be carefully evaluated, considering the slight survival benefit and potential for substantial toxicity incurred with this treatment. The best approach is to design clinical trials that specifically include geriatric assessment to develop active and well-tolerated chemotherapy regimens for elderly SCLC patients. Survival improvement for SCLC patients requires a better understanding of tumor biology and the subsequent development of novel therapeutic strategies. Several targeted agents have been introduced into clinical trials in SCLC, but a minority of these new agents offers a promise of improved outcomes, and negative results are reported more commonly than positive ones. This review focuses on the main issues in the treatment of elderly SCLC patients.     

放疗对局限期和广泛期小细胞肺癌化疗疗效的影响

目的：探讨放疗对局限期和广泛期小细胞肺癌化疗疗效的影响。方法 用寿命表法和Ｌｏｇ－Ｒａｒｋ法分析比较６１例化疗加入疗（化放组）和同期４６例单纯化疗（单化组）小细胞肺癌的生存率。结果：比放组病人１，３，５年生存率分别为７０．５％，２５．４％和１２．９％，而单化组分别为４０．７％，２．６％和２．６％，两组比较有显著差异（Ｐ〈０．０１），在局限期病人中，化放组１－５年生存率明显高于单化组（Ｐ〈０．０２５     

Recent topics in chemotherapy for elderly patients with lung cancer

With the prolongation of life expectancy in Japan, lung cancer is increasing not only in the elderly but also in poor-risk patients who can not undergo standard chemotherapy. Because survival benefits from chemotherapy are clearly expected in patients with small-cell lung cancer (SCLC), standard chemotherapy should be established for the elderly as well as for poor-risk patients with SCLC. We recently reported that the combination of AUC-based carboplatin and a standard dose of intravenous etoposide was an active and relatively nontoxic regimen for elderly patients with SCLC (J Clin Oncol 17: 3540-3545, 1999). Had chemotherapy with concurrent chest irradiation been used for patients with limited disease (LD), better survival might have been achieved in this study. However, Pignon et al. reported that combined chemoradiotherapy in elderly patients with LD-SCLC is a possible poor prognostic factor in their meta-analysis. A recent randomized controlled clinical trial has shown that vinorelbine monotherapy contributed to longer survival in elderly patients with advanced non-small-cell lung cancer (NSCLC), compared to best supportive care. Several retrospective studies have shown that cisplatin can be safely and effectively administered to elderly patients who are eligible for protocol treatment. However, there have been no randomized trials indicating that cisplatin-based combination chemotherapy improves survival in elderly patients with advanced NSCLC, compared to single-agent chemotherapy. Similarly, the role of combined chemoradiotherapy remains controversial in elderly patients with locally advanced NSCLC. Thus, standard therapies proven to be beneficial to non-elderly patients with lung cancer have not always been proven to be beneficial to elderly patients. In order to solve these difficult problems, phase III studies are warranted in elderly or poor-risk patients with lung cancer. Moreover, new agents with relatively low toxicities recently approved in Japan should be applied in clinical trials for the elderly or poor-risk patients with lung cancer.     

血清胃泌素释放肽前体与神经元特异性烯醇化酶水平在小细胞肺癌同步放化疗中的变化及其意义

目的:观察小细胞肺癌（SCLC）患者同步放化疗过程中血清胃泌素释放肽前体（Pro-GRP）与神经元特异性烯醇化酶（NSE）水平的变化情况及其意义。方法:回顾性分析2018年6月至2019年12月山西省肿瘤医院收治的80例SCLC患者资料,分为同步放化疗组（26例）与单纯化疗组（54例）,采用酶联免疫吸附试验（ELISA...     

Treatment of lung cancer--state of the art in 2000

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.     

Concurrent chemoradiation strategies in the management of unresectable stage III non-small-cell lung cancer

Locally advanced or unresectable stage III non-small-cell lung cancer (NSCLC) patients treated with combined-modality therapy with chemotherapy plus thoracic radiation have improved survival compared to those treated with radiotherapy alone. Furthermore, recent studies in good performance status, stage III patients have shown that concurrent chemoradiotherapy improves survival compared to sequential chemoradiotherapy. However, the optimal chemoradiation approach continues to evolve and is the subject of this review. Since the majority of patients completing chemoradiotherapy will succumb to distant metastatic disease, active systemic agents targeting this tumor compartment are required. Recent data suggest that full-dose chemotherapy designed to eradicate distant micrometastases given either as induction or consolidation has the potential to yield improved patient outcomes. Many of these chemotherapeutic agents are also potent radiosensitizers, hence providing enhanced local control. The integration of these chemotherapeutic agents into chemoradiotherapy programs in stage III NSCLC is the focus of current trials. Ongoing research with novel therapeutic agents with activity against distant micrometastases, refined radiation techniques, and enhanced imaging methodologies to aid in accurate staging are being pursued and should lead to improved survival and toxicity outcomes in this disease.     

Current concepts in the diagnosis and management of small-cell lung cancer

Despite a decreasing incidence in the United States, small-cell lung cancer (SCLC) remains a major clinical problem, with approximately 30,000 new cases each year. The diagnosis of SCLC is usually not difficult. The Veterans Administration Lung Study Group (VALSG) staging system is less accurate than the American Joint Committee of Cancer tumor-node-metastasis (TNM) system (7th edition) at predicting survival in SCLC, especially in lower stage disease. Surgery has not played a major part in the management of SCLC, but emerging data suggest that resection may have a role in earlier stage disease. While the frontline treatment of SCLC has not changed significantly in the past decade, newer agents that are currently being investigated provide hope for better treatment of relapsed/refractory disease for the future.     

Systemic Treatment of Small Cell Lung Cancer

Small cell lung cancer (SCLC) accounts for 20–25% of all lung cancer and is characterized by an aggressive clinical course with early dissemination and extremely high risk of recurrence. Chemotherapy has been the cornerstone of treatment, with high response rates including complete responses. Despite the sensitivity of this disease to cytotoxic drugs, the majority of patients will face recurrence and die of the disease within two years. For more than thirty years, investigators have conducted numerous trials using different drug regimens and schedules, as well as different therapeutic modalities. The combination of cyclophosphamide, doxorubicin (adriamycin) and vincristine (CAV) was one of the first widely accepted regimens for the treatment of SCLC. Later, CAV and its hybrids were replaced by the similarly effective but less toxic regimen of cisplatin and etoposide (PE). Clinical investigators have tried different approaches to improve the efficacy of these regimens, such as alternating CAV/PE; consolidation and maintenance therapy; intensive treatment with high-dose chemotherapy; increased frequency of drug administration; or high dose therapy with stem cell support — all with no definitive successes, leaving PE as the standard treatment for patients with SCLC. The recent arrival of new chemotherapy agents such as topotecan, irinotecan, and taxanes may represent a step forward in the treatment of this disease. The most promising regimen is the combination of irinotecan and cisplatin which, according to Japanese investigators, achieves a significantly better survival than standard PE. If validated by confirmatory trials, this combination could well become the new standard treatment for extensive chemotherapy-naïve SCLC. Biological agents are also being widely investigated, including vaccines, matrix metalloproteinase inhibitors, anti-sense therapy, and monoclonal antibodies. Advances in molecular biology will hopefully contribute to progress in the treatment of this lethal disease.     

History of small-cell lung cancer

The history of small-cell lung cancer (SCLC) is one of the more fascinating stories of medicine, a story of hope and disappointment that characterizes it as 1 of the most elusive cancers. Its history can be divided into 3 intervals. The first interval encompassed the 30 years after the initial reports from Bernard in 1926 during which SCLC was characterized. The second interval, from the 1960s-1980s, introduced advances in staging and treatment of SCLC and the advent of chemotherapy and radiation therapy (RT) as the primary forms of therapy. The final interval covers the past 25 years, which is considered a dormant period, although there are some shimmers of hope from the emergence of several new active drugs that are currently undergoing clinical trials.