98 例小细胞肺癌化疗疗效分析

 目的 比较CE方案（CBP、VP-16）、CAP方案（CTX、EPI、DDP）、CE-CAP交替方案治疗晚期小细胞肺癌（Smallcell1ungcancer，SCLC）的临床有效率及不良反应。方法 98例SCLC患者分别接受CE、CAP、CE-CAP交替方案化疗4个周期。结果 三种方案治疗的有效率分别为84．8％、80．4％和81％，差异无统计学意义。不良反应主要为骨髓抑制及消化道反应。骨髓抑制以白细胞减少为主，CE组白细胞Ⅲ度减少发生率为10．8％，CAP组发生率为9．7％，CE-CAP交替方案组9．5％，三组比较差异无统计学意义。消化道反应主要为恶心呕吐，CE组中出现Ⅲ～Ⅳ度胃肠道反应的为13％，CAP组中出现的为25．8％，CE．CAP组中出现的为23．8％，CE组和CAP组、CE-CAP组比较差异有统计学意义，而CAP组和CE-CAP组比较差异无统计学意义。结论 CE、CAP方案、CE-CAP交替化疗是治疗SCLC的较好方案，但CE方案胃肠道副作用较轻，耐受性较好，值得推荐。     

Hospitalization During Chemotherapy for Small Cell Lung Cancer

Ninety patients with small cell lung cancer, who received combination chemotherapy, were studied with regard to hospitalization during the treatment period. Chemotherapy was discontinued in case of tumour progression, or, if progression did not occur, after 18 months. The mean hospitalization time was 18 days per patient which constituted 6.7% of the total tretment time in all 90 patients. The hospitalization rate significantly decreased during the first 10 weeks of treatment, and then remained constantly low, with an average hospital time of 3.7 days per patient during maintenance chemotherapy, accounting for 2% of the total maintenance treatment time. Tumour-associated disability was a major purpose for hospital admissions, accounting for 69% of the hospital time during treatment. Except for the first treatment course, which was routinely given in hospital, chemotherapy was administered on an out-patient basis, and only four patients were admitted to hospital to receive maintenance treatment. In these patients, comorbidity and long-distance living may have contributed to the need for hospitalization. Sixteen patients were admitted to hospital at different times of treatment because of treatment complications, mainly severe infections and haemorrhages. It is concluded, that hospitalization rate is a useful and easily understood treatment outcome measure, which, in our study, implied that patients who responded to chemotherapy also gained an improved social mobility in terms of days outside the hospital, although this should not be interpreted as a comprehensive quality of life measure.     

拓朴替康治疗小细胞肺癌的临床观察

目的:探讨以拓朴替康联合顺铂方案治疗小细胞肺癌(SCLC)的疗效及安全性.方法:观察组60例,化疗方案为TP(拓朴替康 顺铂).拓朴替康1.20mg/m2/d,静滴30min,每日1次,连用5日;DDP 80mg/m2iv gtt,分3天使用.对照组60例,化疗方案为PE(VP-16 顺铂).VP-16 100mg/m2 iv gtt,d1,3,5;DDP 80mg/m2iv gtt,分3天使用.21天为1周期,2个周期评价疗效,1个周期评价不良反应.结果:观察组CR 8例,PR 30例,有效率63.3%,主要不良反应为血液学毒性,非血液学毒性较轻微,一般均可耐受.对照组CR 6例,PR 34例,有效率66.7%.两组间疗效及不良反应均无显著性差异(P＞0.05).结论:拓朴替康联合顺铂化疗方案治疗SCLC有效,局限期疗效优于广泛期.     

Update of Research on Drug Resistance in Small Cell Lung Cancer Chemotherapy

Small cell lung cancer (SCLC) is characterized by a short cell doubling time, rapid progression and earlyoccurrence of blood-borne and lymph metastasis. The malignancy is the highest of all lung cancer types.Although SCLC has a relatively good initial response to chemotherapy as well as radiotherapy, relapse or diseaseprogression may occur quickly after the initial treatment. Drug resistance, especially multi-drug resistance, isthe most important cause of failure of SCLC chemotherapy. This article provides a brief update of research onmechanisms of drug resistance in SCLC and reversal strategies.     

一线化疗方案治疗广泛期小细胞肺癌的网状meta分析

背景与目的顺铂/卡波联合伊立替康/依托泊苷双药化疗方案被推荐为治疗广泛期小细胞肺癌（small cell lung cancer of extensive disease, ED-SCLC）的一线化疗方案。我们在网状meta分析中,通过合成直接证据和间接证据,对推荐的化疗方案的短期疗效进行排序。方法我们在EMBASE、PubMed、CENTARL及clinicaltrial.gov数据库检出了相关疗效比较的随机对照试验。ROB工具被用于评估纳入研究的质量, Stata 13.1被用于统计学合成。结果该研究共纳入10项随机对照研究,共计2,378名患者。与依托泊苷联合卡铂相比,肿瘤的完全缓解率（complete remission rate, CR）在伊立替康联合卡铂组明显提高（OR=3.33,95%CI：1.47-7.54, P<0.05）。伊立替康联合卡铂治疗后CR明显优于依托泊苷联合顺铂（OR=4.09,95%CI：1.18-14.12, P<0.05）。结论本研究结果显示：伊立替康联合卡铂一线治疗ED-SCLC的疗效优于依托泊苷。     

Concurrent Cisplatin-etoposide Chemotherapy plus Thoracic Radiotherapy for Limited-stage Small Cell Lung Cancer

A recent approach in the treatment of limited-stage small celllung cancer (LDSCLC) has involved a combined modality of chemotherapyand chest irradiation. In using the modality, the study of schedulingmethods for combining chemotherapy and radiotherapy should leadto other trials of combined modalities against LDSCLC sinceit is the most basic issue to be evaluated. We have thus conducteda multicenter phase II trial of concurrent cisplatin-etoposide(PVP) chemotherapy and radiotherapy for LDSCLC to determinethe effects of the concurrent administration of a PVP regimenand chest irradiation on response rate, relapse, survival andtreatment toxicity. The chemotherapy regimen consisted of afour-week cycle: cisplatin (80 mg/m², given intravenously onday 1) and etoposide (100 mg/m2, given intravenously on days1–3). This cycle was given four to six times within sixmonths. Chest irradiation to the primary tumors at both thehili and the mediastinum was administered in standard fractionson days 2–12 in the first cycle of chemotherapy and ondays 29–47 in the second cycle, with a total dose of 40–50Gy. Prophylactic cranial irradiation was performed among completeremission (CR) or good partial remission (PR) patients aftercompletion of the concurrent therapy. A total of 66 patientswere entered into the trial and 59 were evaluated. The concurrenttherapy induced an overall response rate of 94.9% in 59 patients:24 patients, 40.7% CR, 32 patients, 54.2% PR. The median responseduration was 8.7 months, and the median survival time for alleligible patients was 14.8 months. The percentage of patientswith two-year survival periods was 20. A local relapse withinthe irradiated area was seen in only 22% of relapsed patients.Brain metastases occurred in 24% of patients. Four of 32 patientstreated with prophylactic cranial irradiation had brain metastases.Toxic effects, chiefly grades 3 and 4 leukopenia, as establishedby the World Health Organization, were detected in all treatedpatients. Other toxicities, including radiation-induced esophagitisand pneumonitis, were deemed almost acceptable. We concludedconcurrent treatment of a PVP regimen with chest irradiationto be a feasible and beneficial therapy with an efficacy compatibleto that of other published reports. The outcome of this protocolwarrants further investigation to determine the optimal typeof schedule for concurrent chemoradiotherapy against LDSCLC.     

局限期小细胞肺癌放化疗综合治疗

[目的]研究常规放疗及加速超分割放疗联合化疗治疗局限期小细胞肺癌的近期疗效及生存期.[方法]1998年2月至2000年5月间,局限期小细胞肺癌共72例随机分为2组,常规放疗组34例和加速超分割放疗组38例.两组接受EP方案化疗2个疗程后开始放疗.常规放疗组2Gy/次,每天1次,每周5次,总量(56～60)Gv/(5.6～6)w.加速超分割组放疗1.4Gy/次,每日2次,2次间隔≥6小时,每周5日,总量56Gy/4w.放射野包括原发灶,同侧肺门、纵隔淋巴引流区.2组病人在完成放疗后继续EP方案化疗4个疗程.[结果]全组总有效率77.8%,中位生存期18个月,常规放疗组和加速超分割放疗组两组近期疗效分别为70.6%和84.2%(P＞0.05),两组1、2、3年生存率分别为76.5%、23.3%、10.9%和80.0%、32.6%、11.7%(P＞0.05).[结论]加速超分割放疗组的近期疗效及长期生存率等同于常规分割放疗组.     

Combination Therapy with Antibody and Interleukin–2 Gene Transfer against Multidrug–resistant Cancer Cells

In the present study, we examined the effect of intcrlcukin–2 (IL–2) gene transfer into multidrug resistance (MDR) cancer cells on the therapeutic efficacy of MRK16. Human MDR ovarian cancer cells, AD10, were transduced with a bicistronic IL–2 retrovirus, Ha–IL2–IRES–Neo. The G418resistant population, IL2–AD10, secreted IL–2 into the culture supernatant and did not form a tumor mass in nude mice. The IL2–AD10 cells were more susceptible to the cytotoxicity of murine spleen cells than AD10 cells in vitro. For examination of the effect of IL–2 gene transfer on the antitumor activity of MRK16 against P–glycoprotein–positlve tumors, IL2–AD10 cells were cotransplanted s.c. with AD10 cells into nude mice in a ratio of 1: 3, and the mice were treated with MRK16 on days 2 and 7. MRK16 markedly inhibited the growth of AD10 cells mixed with IL2 AD10 cells under conditions (0.3–1 jag/body) where it showed only marginal effects on the growth of AD10 tumors. These findings suggest that IL–2 gene transfer potentiates the antitumor activity of MRK16 against MDR tumors.     

免疫检查点抑制剂在小细胞肺癌中的临床研究进展

小细胞肺癌(small cell lung cancer,SCLC)是分化较差的高级别肺神经内分泌肿瘤,尽管仅占所有肺癌的14％左右,但生长迅速、较早出现转移,复发后缺少有效的治疗手段,改善SCLC治疗迫在眉睫.近年来,肿瘤免疫治疗展现了良好的前景,尤其程序性死亡受体1(programmed death1,PD-1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T-lymphocyte-associated antigen 4,CTLA-4)抑制剂的研究正在改变多种实体瘤的临床实践.SCLC与吸烟密切相关,具有较高的肿瘤突变负荷,是免疫治疗潜在理想的肿瘤类型.本文将总结免疫治疗在SCLC的临床研究进展,探讨SCLC免疫治疗中存在的问题、面临的挑战以及未来的应用前景.     

小细胞肺癌的手术治疗

1962到1983年22年间共手术治疗小细胞肺癌50例,其中27例切除(包括4例姑息切除),1例手术死亡。手术切除后4例5年以上健在(其中3例10年健在)。剖胸探查者无5年健在病例。Ⅰ期患者的5年生存率为17.6％,10年生存率为11.8％;Ⅱ期无2年以上生存者;Ⅲ期仅1例10年以上健在。无淋巴结转移的预后优于有转移者。症状期超过半年者切除率甚低。凡术前病理已证实为小细胞未分化癌,尤其是中心型。不适于手术治疗。作者认为辅助放疗和化疗,确能延长患者的生存期,故根治术后皆应辅助放疗和化疗,以期提高疗效。     

A New Quinoline Derivative MS-209 Reverses Multidrug Resistance and Inhibits Multiorgan Metastases by P-glycoprotein-expressing Human Small Cell Lung Cancer Cells

Development of distant metastases and acquired multidrug resistance (MDR) are major problems in therapy for human small cell lung cancer (SCLC). MS-209 is a novel quinoline compound, which reverses P-glycoprotein (P-gp)-mediated MDR. We previously reported that MS-209 reversed in vitro MDR of human SCLC (SBC-3/ADM and H69/VP) cells expressing P-gp. In the present study, we determined the therapeutic effect of MS-209 in combination with chemotherapy against multiorgan metastases of MDR SCLC cells. SBC-3/ADM cells expressing P-gp were highly resistant to etoposide (VP-16), adriamycin (ADM), and vincristine (VCR) in vitro , compared with parental SBC-3 cells lacking P-gp expression. MS-209 restored chemosensitivity of SBC-3/ADM cells to VP-16, ADM, and VCR in a dose-dependent manner in vitro. Intravenous injection with SBC-3 or SBC-3/ADM cells produced metastatic colonies in the liver, kidneys and lymph nodes in natural killer (NK) cell-depleted severe combined immunodeficiency (SCID) mice, though SBC-3/ ADM cells more rapidly produced metastases than did SBC-3 cells. Treatment with VP-16 and ADM reduced metastasis formation by SBC-3 cells, whereas the same treatment did not affect metastasis by SBC-3/ADM cells. Although MS-209 alone had no effect on metastasis by SBC-3 or SBC-3/ADM cells, combined use of MS-209 with VP-16 or ADM resulted in marked inhibition of metastasis formation by SBC-3/ADM cells to multiple organs. These findings suggest that MS-209 reversed the MDR of SBC-3/ADM cells, but not SBC-3 cells, growing in the various organs, and inhibited metastasis formation in vivo. Therefore, this chemosensitizing agent, MS-209, may be useful for treatment of refractory SCLC patients with multiorgan metastases.     

TAM对非小细胞肺癌经NVB-DDP方案诱导耐药性逆转的临床观察

目的:以大剂量三苯氧胺(Tamoxifen,TAM)逆转非小细胞肺癌经多次长春瑞滨-顺铂方案治疗后所产生的多药耐药性,提高疗效。方法:研究前均以流式细胞技术检测患者外周血淋巴细胞(PBL)中P-gp的表达。将72例对长春瑞滨-顺铂方案治疗产生耐药性的非小细胞肺癌患者随机分成两组,每组36例。A组为三苯氧胺治疗组,B组为对照组。A组患者在本次研究中每次化疗前3天及化疗第1、2天口服TAM100mg,每日2次,化疗方案为长春瑞滨25mg/m2,iv,d1,8;顺铂40mg/m2ivd1～3,每28天重复,不少于2周期。B组不服用TAM,仅进行化疗,方案同A组。每周期结束后均检测P-gp的表达并评价临床疗效。结果:两组患者在本研究前PBL中P-gp均呈阳性,A组的总有效率为33.3%(12/36),并有47.2%(17/36)P-gp转阴或显著降低;B组总有效率为13.9%(5/36),P-gp无转阴或显著下降者。经统计学处理,两组临床有效率P<0.01,P-gp转阴率P<0.01,其差异均具有显著性。结论:大剂量TAM对经多次长春瑞滨-顺铂方案治疗后产生了耐药性的患者有较好的逆转作用,可使疗效再次提高。     

小细胞肺癌患者血清神经元特异性烯醇酶水平的动态观察

目的：探讨小细胞肺癌患者病程中血清神经元特异性烯醇酶（NSE）水平变化的临床意义。方法：采用ABC－ELISA法测定32例小细胞肺癌（SCLC）,50例非小细胞肺癌（NSCLC）,50例志愿正常成人血清中NSE,并动态观察其中27例SCLC治疗前后,20例SCLC复发前后NSE的变化。结果：SCLC组血清NSE含量明显高于其它2组（P＜0．001）,NSE对SCLC的敏感性为81．3％,特异性为96％;其中27例SCLC经综合治疗后,病情缓解者（CR或PR）血清NSE明显下降（P＜0．01）,而病情无好转者（PD或NC）血清NSE持续升高;20例SCLC病情复发或进展后,血清NSE再次显著升高（P＜0．01）;7例患者复发前3个月NSE检测,发现3例阳性。结论：SCLC血清NSE水平变化与病情变化相一致,可作为SCLC的辅助诊断、疗效判定、预测复发的有用指标。     

肺小细胞癌与神经元Hu抗体免疫学研究

［目的］探讨肺小细胞癌导致的神经系统副肿瘤综合征的发病机理。（方法）用免疫细胞化学和免疫印迹技术测定13例肺小细胞癌件神经系统副肿瘤综合征患者血清及脑脊液中的神经元抗体——Hu抗体，并用Schuller公式计算鞘内免疫球蛋白IgG合成及Hu抗体特异活性。［结果］13例肺小细胞癌伴神经系统副肿瘤综合征患者血清及脑脊液中的Hu抗体阳性，11例中枢神经系统中有抗体合成，9例脑脊液中抗体特异活性增高。[结论]肺小细胞癌导致的神经系统副肿瘤综合征是一种自身免疫性疾病，Hu抗体在致病过程中起重要作用，而且对于肺小细胞癌的临床早期诊断有重要的临床价值。