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.     

足叶乙甙联合铂类一线化疗后复发的小细胞肺癌二线化疗的临床研究

目的：本研究旨在分析敏感性复发及难治性复发的小细胞肺癌的二线化疗效果。方法：2003年1月-2006年3月经足叶乙甙联合铂类一线化疗后复发的小细胞肺癌（SCLC）共64例,其中敏感性患者复发31例,难治性患者复发33例。对难治性复发或敏感性复发时间少于6月者,采用紫杉类或伊立替康单药化疗;对敏感性复发时间大于6月者仍采用原一线方案或更改为紫杉类或伊立替康单药化疗。结果：64例患者进行了二线化疗,有57例患者可评价疗效,二线治疗总有效率22．8％,中位疾病进展时间（mTTP）15．1周,中位生存期（MST）7．2月。敏感性复发组及难治性复发组的有效率（CR＋PR）分别为37．9％和7．1％（P〈0．01）,mTTP分别为15．9周和10．4周（P〈0．05）,MST分别为9．0月和6．0月（P〈0．05）。骨髓抑制为二线化疗的主要不良反应,敏感性复发组及难治性复发组G3／4级白细胞减少发生率分别为41．9％和42．4％,G3／4级血小板减少发生率分别为22．6％和30．3％,两组不良反应无明显差异（P〉0．05）。结论：足叶乙甙联合铂类一线化疗后复发的小细胞肺癌采用二线化疗有部分病例仍有效,特别是对于敏感性复发的患者。     

非小细胞肺癌二线化疗现状

近年来 ,一些治疗非小细胞肺癌(ＮＳＣＬＣ)比较有效的新药不断问世。临床试验结果表明 :某些单药或联合用药治疗ＮＳＣＬＣ优于最好的支持治疗 (ＢＳＣ) ,使人们不再怀疑化学治疗在晚期ＮＳＣＬＣ治疗中的作用 ,化学治疗已成为晚期ＮＳＣＬＣ的常规治疗。然而晚期ＮＳＣＬＣ仍然是一个化疗相对耐药的肿瘤 ,单一化疗难以根治 ,实际上即使初始有效的患者终究也要复发。其中行为状态 (ＰＳ)评分较好、有条件接受再次化疗的晚期ＮＳＣＬＣ患者必然面对一个二线化疗的问题。本文拟就近年来ＮＳＣＬＣ二线化疗加以讨论。1　单药二线治疗晚期ＮＳ…     

复发或难治性非小细胞肺癌的化疗进展

对含铂类药物治疗后复发的非小细胞肺癌,单药泰索帝为标准的二线化疗药物,可明显延长病人的生存时间及改善生活质量.一项泰索帝的Ⅲ期随机对照研究证实,多靶点叶酸抑制剂的抗代谢药Alimta二线化疗治疗非小细胞肺癌,其疗效、中位生存时间及1年生存率与泰索帝相似,可替代泰索帝成为晚期NSCLC的二线化疗药物.泰索帝与健择、卡铂、伊立替康、EGFR-TK抑制剂及抗血管生成剂联合化疗,有一定的疗效.TXT为复发的NSCLC常用的二线标准治疗方案.Alimta为备用的二线治疗方案.Iressa单药对铂类及泰索帝失败后的晚期非小细胞肺癌仍然有效.     

非小细胞肺癌EGFR-TKI靶向治疗和标准二线化疗临床疗效的Meta分析

目的:比较NSCLC患者EGFR-TKI靶向治疗和标准二线化疗的临床疗效.方法:通过计算机文献检索中英文数据库,收集国内外公开发表的有关EGFR-TKI靶向治疗和标准二线化疗的随机对照试验,采用Cochrane协作网提供的Review Manager 5.2软件进行Meta分析.结果:经过筛选文献,共8篇RCT纳入研究.Meta分析结果显示,两组OS、PFS的HR值及ORR的RR值分别为1.01(0.92,1.10)、0.90(0.74,1.08)及1.48(1.20,1.81).结论:就OS及PFS而言,两组患者临床疗效相似,无统计学差异.但是靶向治疗组ORR优于化疗组.     

非小细胞肺癌辅助化疗研究进展

近年来,非小细胞肺癌(NSCLC)术后辅助化疗的Ⅲ期随机临床试验结果已陆续报道,术后辅助化疗逐渐被接受,已成为Ⅱ～ⅢA期非小细胞肺癌综合治疗的重要措施之一.本文就NSCLCⅢ期随机临床试验结果作一综述.     

依立替康联合顺铂二线治疗小细胞肺癌

背景与目的:小细胞肺癌(small cell lung cancer,SCLC)一线化疗疗效较好,然而一旦复发,治疗十分困难,目前尚未确定最佳二线化疗方案。因此,我们采用依立替康(irinotecan,CPT-11)联合顺铂(cisplatin,DDP)二线治疗SCLC,以探讨其疗效与安全性。方法:对30例既往经一线化疗方案治疗失败的SCLC患者采用CPT-1160mg/m2,静滴,第1、8、15天;DDP25mg/m2,静滴,第1~3天。28d为1个周期,2个周期后进行一次疗效评价,4周后复核并随访生存期。结果:可评价病例28例,其中CR1例,PR7例,SD8例,PD12例,有效率28.6%(8/28)。中位疾病进展时间(time to progression,TTP)为3.2个月(0.8~5.6个月),二线治疗生存期7.5个月(1.5~31个月),可使总体生存期达到15个月(2.3~43.5个月)。主要不良反应为血液毒性,Ⅲ~Ⅳ度中性粒细胞下降36.7%(11/30),其次是肝功能损害,仅1例出现Ⅲ度腹泻。结论:CPT-11联合DDP二线治疗SCLC是可行、安全及有效的。     

非小细胞肺癌的术前化疗

我科从1985年3月至1988年9月,对59例中晚期非小细胞肺癌,进行了术前大剂量PVE(C)联合化疗,治疗结果报告如下: 全部病例均经病理组织学或细胞学诊断证实。年龄26—69岁;男43例,女16例;Ⅰ期1例,Ⅱ期27例,Ⅲ期31例;鳞癌42例,腺癌17例。 本组对拟行手术治疗的病例均常规行术前化疗,部分不很适宜手术治疗的病例亦先行化疗,部分治疗有效病例再行手术。     

二线不同化疗方案治疗小细胞肺癌的疗效和安全性比较

目的 比较二线不同化疗方案治疗小细胞肺癌的疗效和安全性.方法 按照二线治疗方案不同将84例接受二线方案化疗的小细胞肺癌患者分为伊立替康组38例、依托泊苷组24例和紫杉醇/多西他赛组22例,分别给予伊立替康、依托泊苷、紫杉醇/多西他赛治疗.观察3组患者化疗近期疗效、总生存时间(OS)、无进展生存时间(PFS)以及不良反应发生情况.结果 3组患者DCR、ORR比较,差异无统计学意义(P>0.05);3组患者OS和PFS比较,差异无统计学意义(P>0.05).伊立替康组Ⅲ~Ⅳ度腹泻发生率明显高于其他2组,差异具有统计学意义(P<0.05);3组患者Ⅲ~Ⅳ度白细胞减少、贫血、血小板减少、乏力、恶心/呕吐、ALT升高、AST升高发生率比较,差异无统计学意义(P>0.05).结论 不同二线化疗方案对一线化疗失败者效果均确切,生存期相近,不良反应除伊立替康组腹泻发生率稍高外,其他Ⅲ~Ⅳ度不良反应发生率均相近.     

晚期非小细胞肺癌的解救化疗

化疗在非小细胞肺癌（NSCLC）综合治疗中的作用日益受到重视，临床上辅助化疗与新辅助化疗渐趋增多，但晚期与复发的患者仍是主要对象。80年代确定的顺铂（DDP）为基础的化疗治疗晚期NSCLC患者有效率（RR）提高达50％左右，且能改善中位生存期（MST），从4月增到7月－8月。90年代出现一些新药，如：紫杉醇（Taxol,TAX)与紫杉特尔（Docetaxel,DOC)、氟胞苷（Gemcitabine,GEM)、伊利特肯（Irinotecan,CPT-11)和去甲长春花碱（Vinorelbine,NVB)等单用RR＞20％，与DDP或卡铂（CBP）联合应用，MST可达9月－10月，1年生存率亦有提高。然而，有些患者，特别是老人与肾功能不良者；不能耐受含DDP方案者，特别是老人与肾功能不良者；不能耐受含DDP方案者；或经含铂的第一线方案治疗失败者；患者活动状况（PS）差或病变恶化者需要交替方案。近年来，积极探索以非铂为基础的解求方案渐趋增加，以期应用新抗癌药，单剂、序贯或组成非铂的联合化疗，力求延长生存期，导致最小的不良反应，控制疾病症状和改善生活质量（QOL）。     

小细胞肺癌二线治疗的新进展

小细胞肺癌（ＳＣＬＣ）是一种恶性程度极高且预后差的恶性肿瘤,约占肺癌的１５％ ～２０％,其初始对化疗敏感,但极易复发。复发后二线治疗的选择至今仍是难题,目前尚无确切证据证实二线化疗优于最佳支持治疗。拓扑替康是目前唯一批准用于ＳＣＬＣ二线化疗的药物。此外,多种靶向治疗药物也已进行了临床试验。本文将对ＳＣＬＣ二线治疗药物及进展进行综述。     

吉西他滨联合顺铂方案二线治疗晚期非小细胞肺癌的临床观察

目的：观察吉西他滨联合顺铂二线治疗晚期非小细胞肺癌的疗效及毒性反应。方法：从2000年3月～2004年10月对38例晚期非小细胞肺癌患者采用二线化疗,入组患者均经病理组织学证实,有可测量病灶,具体为吉西他滨1000mg／m。第1、8天,顺铂80mg/m^2,分3天应用,21天为1个周期。化疗2个周期后评价疗效及毒副反应。结果：所有患者均可评价,总共进行108周期的化疗。完全缓解（CR）0例,部分缓解（PR）11例,稳定（SD）12例,进展（PD）15例,总有效率28．9％。中位缓解时间4．5月,中位生存时间7．8月。主要不良反应为血液学毒性,其中Ⅲ／Ⅳ度的中性粒细胞下降、血小板下降和血红蛋白下降分别为18．5％（20／108）、11．1％（12／108）和8．3％（9／108）。其次为消化道毒性,Ⅲ／Ⅳ度的食欲下降和恶心呕吐分别为13．9％（15／108）和12．0％（13／108）。结论：吉西他滨联合顺铂对复治晚期非小细胞肺癌有较好疗效,毒副反应可以耐受。     

Phase II study of weekly chemotherapy with paclitaxel and gemcitabine as second-line treatment for advanced non-small cell lung cancer after treatment with platinum-based chemotherapy

Purpose We evaluated the tolerability and activity of the combination of weekly paclitaxel (PTX) and gemcitabine (GEM) in second-line treatment of advanced non-small cell lung cancer (NSCLC) after treatment with platinum-based chemotherapy. Patients and methods PTX (100 mg/m²) and GEM (1,000 mg/m²) were administered to patients with previous treated NSCLC on days 1 and 8 every 3 weeks. Results A total of 40 patients (performance status 0/1/2, 7/27/6 pts) were enrolled. The response rate was 32.5% (95% confidence interval: 18.0–47.0%). The median survival time was 41.7 weeks (95% confidence interval: 28.5–54.7 weeks). The median time to disease progression was 19 weeks. Hematological toxicities (grade 3 or 4) observed included neutropenia in 60%, anemia in 15%, and thrombocytopenia in 12.5% of patients. Non-hematological toxicities were mild, with the exception of grade 3 diarrhea, pneumonitis, and rash in one patient each. There were no deaths due to toxicity. Conclusion The combination of weekly PTX and GEM is a feasible, well-tolerated, and active means of second-line treatment of advanced NSCLC.     

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer

Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m²) followed by mitomycin C (8 mg/m²) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3–4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6–21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.     

Doublet regimen of cisplatin plus docetaxel for second-line chemotherapy after prior therapy with cisplatin plus irinotecan for non-small cell lung cancer: a phase II study

Background To evaluate the safety and efficacy of second-line chemotherapy with docetaxel and cisplatin for non-small cell lung cancer (NSCLC), we performed a phase II study.Methods The subjects were 25 patients with NSCLC, 75 years or younger, without organ dysfunction (performance status [PS], 0 to 2) in whom treatment with cisplatin and irinotecan had been ineffective or had been followed by recurrence or relapse. Four weeks or more after the end of the previous therapy, 60mg/m² of cisplatin and 60mg/m² of docetaxel were administered at intervals of 3 weeks.Results Observed toxicities of grade 3 or 4 included anemia (24% of patients), leukocytopenia (48%), neutropenia (76%), thrombocytopenia (4%), hepatic dysfunction (8%), and electrolyte abnormalities (4%). However, no severe nonhematologic adverse reactions occurred. The overall response rate was 32% (95% confidence interval, 13.7–50.3). The median time to disease progression was 98 days, and the median survival time was 257 days.Conclusion Our results suggest that cisplatin and docetaxel can be used as second-line chemotherapy against NSCLC. But further, comparative, study of this combination should be performed in patients with good PS and organ function who have responded to prior platinum-based chemotherapy.     

联合化疗加放射治疗局限期小细胞肺癌

回顾性分析局限期小细胞肺癌６０例，ＡＤＭ、ＤＤＰ、ＶＰ－１６、ＣＴＸ联合化疗加胸部（６０）Ｃｏ放疗，ＤＴ５０～６０ＧＹ／６～７周。放疗结束后２个月左右复查，将获得ＣＲ的４９例，采用随机分组分为预防性全脑照射组（ＰＣＩ）２５例及对照组２４例。结果为生存时间与ＫＰＳ计分和ＣＥＡ值明显相关，而与是否行脑预防照射无明显差异。     

A multicenter phase II study of belotecan, a new camptothecin analogue, as a second-line therapy in patients with small cell lung cancer

Belotecan (Camtobell, CKD602) is a new camptothecin derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this phase II study was to evaluate the efficacy and safety of single agent belotecan as a second-line therapy in patients with small cell lung cancer (SCLC).Patients who were previously treated for SCLC were entered into the study. Belotecan was given by daily intravenous infusion for five consecutive days, every three weeks.Twenty-five patients were enrolled in this study. On an intention-to-treat basis, belotecan induced an overall response rate of 24%, a median overall survival of 9.9 months, a median time to progression of 2.2 months, and a 1-year survival rate of 38.3%. Grade 3/4 neutropenia developed in 88.0% of patients and grade 3/4 thrombocytopenia in 40.0%. Nonhematologic toxicity of grade 3 or 4 was low.The results suggest that belotecan is relatively active and well tolerated as a second-line agent in patients with SCLC.     

多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.     

A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer

Purpose  To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC). Patients and methods  Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks. Results  Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1–21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7–53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur. Conclusion  S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.