伊立替康联合顺铂与拓扑替康联合顺铂二线治疗小细胞肺癌的比较研究

目的：回顾性观察伊立替康联合顺铂（IP组）与拓扑替康联合顺铂（TP组）二线治疗难治型小细胞肺癌的近期、远期疗效及毒副作用。方法：共62例患者，均为一线EP方案治疗失败且在3～6个月内出现进展，IP组：伊立替康60mg／m^2，第1、8天，DDP25mg／m^2，第1～3天，静脉滴注；TP组：拓扑替康0．75mg／m^2，第1—5天，DDP25mg／m^2，第1～3天，静脉滴注。均21天为1周期。每2个周期评价疗效。结果：IP组30例，有效率33，3％（10／30），TP组32例，有效率37．5％（12／32），两组近期疗效无差异（P〉0．05）。两组中位疾病进展时间（mTFP）均为3．0个月；中位生存期（MST）分别为12个月和11．5个月，无显著性差异（P〉0．05）。两组毒副作用主要表现为：Ⅲ-Ⅳ度粒细胞下降TP组高于IP组（31．3％vs．23．3％），但两组无显著性差异（P〉0．05）；Ⅲ-Ⅳ度血小板下降TP组高于IP组（18．8％vs．6．6％），两组有显著性差异（P〈0．05）；延迟性腹泻IP组高于TP组（30．0％vs．3．1％）。结论：伊立替康联合顺铂与拓扑替康联合顺铂二线治疗难治型小细胞肺癌均取得较好疗效，两方案毒副作用均可以耐受。     

伊立替康联合氟尿嘧啶/亚叶酸钙方案一线治疗37例晚期大肠癌

背景与目的：伊立替康联合氟尿嘧啶／亚叶酸钙方案为晚期大肠癌一线治疗的标准方案。本研究观察伊立替康联合氟尿嘧啶／亚叶酸钙双周（CPT—11＋5FU／LV双周FOLFIRI）方案一线治疗晚期大肠癌的客观有效率及不良反应。方法：2001年5月-2005年3月，37例晚期大肠癌患者接受FOLFIRI方案一线治疗。化疗剂量为CPT—11 180mg／m^2静脉点滴第1天，亚叶酸钙（LV）200mg／m^2静脉点滴第1、2天，5．FU400mg／m^2静推第1、2天，5-FU600mg／m^2持续泵注44小时第1、2天，14天为1周期。结果：36例可评价疗效患者有效率为41。7％。Ⅲ／Ⅳ度骨髓抑制发生率占总人数的35．1％和8．1％，4例患者出现中性粒细胞减少性发热。Ⅲ度迟发性腹泻发生率为8．1％：结论：伊立替康联合氟尿嘧啶／亚叶酸钙双周方案（FOLFIRI）是一线治疗晚期大肠癌安全而有效的方案。     

两种方案治疗广泛期小细胞肺癌的临床观察

目的：比较两种不同化疗方案治疗广泛期小细胞肺癌的临床疗效及毒副反应。方法：回顾性分析2010年1月至2013年1月,我院肿瘤科住院治疗的70例广泛期小细胞肺癌患者的临床资料,分为伊立替康（ IP）组和VP-16（EP）组,每组各35例患者,其中伊立替康组患者采用伊立替康联合顺铂方案化疗, VP-16组患者采用VP-16联合顺铂方案化疗,观察两组方案治疗患者的近期临床效果和毒副反应情况。结果：伊立替康（ IP）组和VP-16（EP）组患者的有效率分别为74．28%（26/35）和71．42%（25/35）,两组比较差异无统计学意义（P〉0．05）;无进展生存期分别是4．3个月和3．7个月（ P〉0．05）,总生存期分别是9．3个月和8．9个月（ P〉0．05）。伊立替康（ IP）组的主要不良反应是粒细胞减少、血小板减少、贫血、腹泻、消化道反应,发生率分别为54．29%、14．29%、25．71%、22．86%、71．43%,VP-16（EP）组的主要不良反应反应为粒细胞减少、血小板减少、贫血、腹泻、消化道反应,发生率分别是80．0%、60．0%、54．29%、2．86%、74．29%。结论：IP和EP方案一线治疗广泛期小细胞肺癌的疗效和生存期无显著差异,不良反应均可耐受。     

伊立替康联合磁感应热疗对小细胞肺癌细胞增殖、凋亡及周期的影响

目的:探讨伊立替康联合磁感应热疗对H446细胞的作用效果。方法:研究检测磁性介质的升温性能,以及磁性介质与人小细胞肺癌H446细胞的生物相容性。将小细胞肺癌H446细胞予伊立替康、磁感应热疗及磁感应热疗联合伊立替康三种不同干预措施,采用CCK-8法检测H446细胞活力,并使用流式细胞仪检测H446细胞凋亡率及周期变化。结果:磁性介质升温性能良好且毒性小;磁感应热疗联合伊立替康20%抑制率浓度干预后,细胞抑制率为（36.58±2.10）%,细胞凋亡率为（28.90±3.64）%,均明显高于磁感应组和伊立替康组（P均＜0.01）;细胞周期阻滞于G2/M、S期。结论:磁感应热疗可抑制H446细胞增殖、促进凋亡,与伊立替康联合应用时具有相加抗肿瘤作用,但对细胞周期作用不明显。     

依立替康在进展期非小细胞肺癌中的应用

依立替康（CPT－11）为半合成水溶性喜树碱衍生物，对氟尿嘧啶难治性转移性结直肠癌有明确的疗效，也应用于肺癌、卵巢癌、子宫颈癌。本文对目前进行的CPT－11在进展期非小细胞肺癌（NSCLC）的临床试验进行综述，包括CPT－11联合铂类或非铂类化疗药物及CPT－11的三药联合化疗方案，评价其在进展期NSCLC中的作用。     

拓扑替康抑制HL-60细胞增生和诱导凋亡机制与c-myc的关系

目的探讨拓扑替康（TPT）抑制白血病细胞的作用机制。方法采用反转录-聚合酶链反应（RT-PCR）和免疫组织化学方法,检测TPT作用后c—myc mRNA及其蛋白的表达情况。结果0．15μmol／L TPT作用HL-60细胞12h后,HL-60细胞c—myc mRNA表达为0．17±0．03,与空白对照组的1．11±0．25相比明显降低,差异具有统计学意义（P〈0．05）。HL-60细胞c—myc蛋白表达阳性细胞百分率为19．67％,较空白对照组的68．33％明显降低,差异具有统计学意义（P〈0．05）。结论拓扑替康抑制HL-60细胞增生和诱导凋亡可能是通过c—myc途径起作用的。     

IP方案二线治疗复发性小细胞肺癌的临床观察

目的：临床观察伊立替康联合顺铂方案二线治疗21例复发性小细胞肺癌的近期疗效和不良反应。方法：21例复发小细胞肺癌患者接受IP方案化疗2周期,观察客观缓解率和不良反应。分层分析难治性患者（初次缓解时间不足90天）和非难治性患者（缓解期≥90天）的缓解率差异。结果：21例患者总有效率为38．1％。初治缓解时间不足90天的9例患者中,疗效为11％（1／9）,初治缓解时间≥90天的12例患者中,疗效为58．3％（7／12）,两组间有显著差异。主要不良反应是消化道反应和血液学毒性。结论：伊立替康联合顺铂是治疗复发性小细胞肺癌安全、有效的方案。     

伊立替康联合顺铂方案治疗复治性晚期小细胞肺癌23例临床观察

目的观察伊立替康联合顺铂方案治疗复治性晚期小细胞肺癌的疗效和安全性。方法伊立替康联合顺铂治疗23例复发或进展的小细胞肺癌，伊立替康60mg／m^2静脉滴注，d1,8,15，DDP60mg／m^2静脉滴注，d1；每28d为1个周期。结果23例均可评价疗效，完全缓解率为13％（3／23），部分缓解率为30.4％（7／23），总有效率CR＋PR为43.5％；稳定6例（26．1％），进展7例（30．4％），中位疾病进展时间为4、6个月，中位生存期为8、3个月。主要毒副反应为血液学毒性和消化道症状，其中Ⅲ、Ⅳ度白细胞减少发生率为65．2％（15／23）；血小板减少发生率为34．8％（8／23）；恶心呕吐发生率为82．6％（19／23）；腹泻发生率较高，为87、0％（20／23），其中Ⅲ、Ⅳ度腹泻为56．5％（13／23）。全组无毒性相关死亡。结论伊立替康联合顺铂作为二线方案治疗复治性晚期小细胞肺癌有较好的疗效，毒副反应可以耐受。     

伊立替康联合奈达铂一线治疗广泛期小细胞肺癌的临床观察

目的评价伊立替康（CTP-11）联合奈达铂一线治疗广泛期小细胞肺癌的疗效及不良反应。方法 48例经病理或细胞学诊断为广泛期小细胞肺癌患者接受伊立替康90mg/m2,d1、8;奈达铂80mg/m2,分3天静脉滴注。每3周为1个周期,用药至疾病进展或化疗相关毒副反应不能耐受时观察疗效。结果 48例入选患者均可评价疗效,有效率为89.6%,疾病控制率达95.8%,中位总生存期为13.5个月,中位无疾病进展时间（TTP）为7.6个月。主要不良反应为Ⅲ/Ⅳ度中性粒细胞下降（33.3%）、腹泻（16.7%）和恶心、呕吐（4.2%）等。结论伊利替康联合奈达铂一线治疗广泛期小细胞肺癌安全、有效,可作为一线化疗方案的选择。     

伊立替康联合替吉奥二线治疗转移性大肠癌的临床观察

目的：研究伊立替康联合替吉奥二线治疗转移性大肠癌的临床疗效及不良反应.方法：对经病理检查确诊同时影像学证实有一个或一个以上脏器转移的36例转移性大肠癌患者,采用伊立替康联合替吉奥方法治疗.替吉奥胶囊80mg/（m2·d）,早、晚餐后口服,d1-14.伊立替康60mg/m2,第1、8天.每3周重复,2个周期后评价疗效同时记录不良反应.结果：全组36例病例中CR 2例（5.56％）,PR 11例（30.56％）,SD 10例（27.78％）,PD 13例（36.11％）,总有效率36.11％.主要不良反应为乙酰胆碱综合症、延迟性腹泻、中性粒细胞减少、胃肠道反应等,无治疗相关性死亡.结论：伊立替康联合替吉奥二线治疗转移性大肠癌有效率较好,不良反应可耐受,是转移性大肠癌患者较为理想的化疗方案.     

三药联合化疗和单药拓扑替康二线治疗小细胞肺癌的疗效和安全性比较

  目的  比较顺铂、依托泊苷、伊立替康联合化疗方案和单药拓扑替康二线治疗敏感复发型小细胞肺癌(smalll cell lung cancer, SCLC)的疗效和安全性。  方法  收集2014年9月至2017年9月吉林省肿瘤医院就诊78例患者资料, 筛选敏感复发型小细胞肺癌患者, 其中36例患者给予顺铂、依托泊苷、伊立替康联合化疗方案, 42例患者给予单药拓扑替康化疗。联合化疗组药物用法:顺铂25 mg/m2, 第1天、第8天静脉滴注; 依托泊苷60 mg/m2, 第1、2、3天静脉滴注; 伊立替康90 mg/m2, 第8天静脉滴注, 连续给予5个2周方案的化疗。单药拓扑替康组药物用法:拓扑替康1.5 mg/m2, 第1~5天静脉滴注, 每3周1个周期。评价两组治疗方案的无进展生存时间(progressionfree survival, PFS)、总生存时间(overall survival, OS)及安全性。  结果  联合化疗组中位无进展生存时间(mPFS)5.3个月(95% CI:4.3~ 5.8), 拓扑替康组mPFS 3.2个月(95% CI:2.7~4.0), 差异具有统计学意义(P=0.003 0);联合化疗组中位总生存时间(mOS)16.3个月(95% CI:13.8~19.1), 拓扑替康组mOS 13.1个月, 差异具有统计学意义(P=0.009 7)。联合化疗组和单药拓扑替康组常见的3/4级不良事件主要有中性粒细胞下降[31例(86.1%) vs.28例(66.7%)]、白细胞下降[29例(80.6%) vs.21例(50.0%)]、贫血[26例(72.2%) vs.10例(23.8%)]、血小板下降[13(36.1%) vs.11(26.2%)]。联合化疗组发生1例治疗相关死亡(发热性中性粒细胞下降合并肺部感染), 拓扑替康组无治疗相关的死亡发生。  结论  顺铂、依托泊苷、伊立替康联合化疗方案比单药拓扑替康疗效更好, 可考虑作为敏感复发型SCLC患者二线化疗的备选方案之一。两种化疗方案毒性均可耐受, 但联合化疗组不良事件发生率更高, 应进一步探索更为合适的化疗剂量。      

拓扑替康单药治疗小细胞肺癌临床研究

目的探讨拓扑替康单药治疗小细胞肺癌(SCLC)的疗效及安全性.方法初治和复治(SCLC)40例,可评价疗效35例,可评价不良反应40例.拓扑替康1.2mg·m     

拓扑替康和卡铂新辅助化疗结合手术治疗16例小细胞肺癌的临床观察

目的:探讨拓扑替康为主的新辅助化疗和手术治疗小细胞肺癌的临床疗效及特点.方法:从2002年10月至2004年2月对16例小细胞肺癌患者进行术前化疗,拓扑替康1.5mg/(m2·d),连用5天,卡铂400mg/(m2·d),用1天,共化疗2个周期.休息4周后进行手术治疗.结果:化疗后疗效评价为完全缓解1例,部分缓解6例,好转6例,稳定2例,病变进展1例.临床缓解率为43.8%.2例全肺切除,14例肺叶切除加淋巴结清扫术.手术后1年生存率为75.0%,其中4例1年内死亡.结论:拓扑替康加卡铂新辅助化疗后,手术治疗的疗效优于单一方法治疗,患者可以耐受此方案化疗的不良反应,近期疗效肯定,为提高长期生存率提供了条件.     

A phase II study of irinotecan (CPT-11) and carboplatin in patients with limited disease small cell lung cancer (SCLC)

PURPOSE: The aim of this phase II trial was to evaluate the efficacy and safety of a combination chemotherapy containing irinotecan (CPT-11) and carboplatin as first-line treatment of patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: From December 2002 to May 2004 61 patients with limited disease (IASLC classification) were enrolled who were not suitable for concurrent chemo-radiotherapy. Eighteen of the 61 patients (29.5%) had malignant pleural or pericardial effusion and 4 patients (6.6%) had involved supra- or infraclavicular lymph nodes. Patients received irinotecan 50mg/m(2) on days 1, 8 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. RESULTS: A total of 233 chemotherapy cycles were administered. The median number of cycles per patient was 4. The overall response rate to chemotherapy on an intention-to-treat basis was 64%. The median overall survival was 13.8 months, the median disease-free survival 8.0 months, the 1-year survival rate 53.5%, and the 2-year survival rate 17.9%. Haematological and non-hematogical toxicities were low (CTC-grade 3 neutropenia 14.8%, grade 3 thrombocytopenia 5.2%, grade 3/4 anemia 5.1%, grade 3 nausea/vomiting 5.1%, grade 3 diarrhea 3.6%, grade 3 alopecia 3.6% of pts). CONCLUSION: The results suggest that the combination of irinotecan (CPT-11) and carboplatin is active and well tolerable in patients with limited disease SCLC who were not suitable for concurrent chemotherapy.     

Recent advances with topotecan in the treatment of lung cancer

Topotecan is a semisynthetic derivative of camptothecin that specifically targets topoisomerase I. It has well-established antineoplastic properties and has been successfully combined with other antineoplastic agents with activity dependent on DNA disruption, such as cisplatin and etoposide. Topotecan is indicated for the treatment of small cell lung cancer (SCLC) sensitive disease after failure of first-line chemotherapy and metastatic ovarian carcinoma after failure of initial or subsequent chemotherapy. Since the approval of topotecan for the second-line treatment of SCLC, studies have been conducted in the first-line setting. Recent studies demonstrate the utility of i.v. topotecan in combination with cisplatin for untreated SCLC. Further, an oral formulation of topotecan is currently under investigation and may provide added convenience for patients. Oral topotecan has been studied in the first- and second-line settings for both SCLC and non-small cell lung cancer (NSCLC). Three recent phase III trials have demonstrated the activity of oral topotecan. In the first study of chemotherapy-na?ve patients with extensive-disease SCLC, oral topotecan plus cisplatin provided efficacy and safety similar to those of etoposide plus cisplatin. In a second study of patients with relapsed SCLC, treatment with oral topotecan showed a statistically significant and clinically meaningful longer overall survival time and improvement in dyspnea and quality of life compared with best supportive care alone in all prognostic groups. Finally, in previously treated patients with NSCLC, single-agent oral topotecan was shown to be noninferior in 1-year survival rate relative to the current standard of i.v. docetaxel. In future studies, oral topotecan will represent a good candidate for combination therapy with other i.v. or oral chemotherapy agents, monoclonal antibodies, and small molecule tyrosine kinase inhibitors.     

A phase I study of 3-day topotecan and cisplatin in elderly patients with small-cell lung cancer

Purpose: The aim of this phase I study was to determine the maximum-tolerated dose (MTD) in elderly patients with small-cell lung cancer (SCLC). Patients and methods: Patients aged over 75 years with previously untreated SCLC were enrolled in this study. Both topotecan and cisplatin were administered on days 1–3 and repeated every 3 weeks. The starting dose of topotecan was 0.5 mg/m²/day, while cisplatin was fixed at the dose of 20 mg/m²/day. Patients with limited disease (LD) SCLC received thoracic irradiation after the completion of chemotherapy. Results: Twenty-one elderly patients were enrolled in this study and received a total of 59 cycles. The major hematological toxicity was neutropenia and non-hematological toxicities including diarrhea were generally mild and reversible. The MTD of topotecan was determined as 1.2 mg/m²/day. The recommended phase II study dose of topotecan was determined as 1.0 mg/m²/day with cisplatin 20 mg/m²/day daily for 3 days. An objective response was observed in 6 of 10 patients (60%) with LD-SCLC and 6 of 11 (55%) with extensive disease (ED) SCLC. The median survival time in patients with LD-SCLC and those with ED-SCLC were 16.0 and 11.0 months, respectively. Conclusion: The combination chemotherapy of 3-day topotecan and cisplatin appears to be tolerable and effective in elderly patients with SCLC.     

Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan.

Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action. Topotecan (TPT), a hydrophilic derivative of camptothecin, is currently undergoing phase II clinical trials in small-cell lung cancer (SCLC). Human SCLC OC-NYH cells were made more than 6-fold resistant to topotecan by stepwise drug exposure and resistance was stable for 70 passages without drug. NYH/TPT cells had half the topoisomerase I level and activity of wild-type cells. However, no difference in camptothecin or topotecan inhibition of topoisomerase I-mediated DNA relaxation was found, indicating that the enzyme itself was unchanged in the resistant cell. In NYH/TPT cells, topoisomerase II alpha and beta levels were increased approximately 2-fold. Accordingly, the topoisomerase II-directed drug etoposide (VP-16) induced an increased number of DNA single-strand breaks in NYH/TPT cells. However, sensitivity to different topoisomerase II-targeting agents in NYH/TPT cells varied from increased to decreased, indicating a role for as yet unidentified factors acting on the pathway to cell death after topoisomerase II-induced DNA damage has occurred. Of 20 anti-cancer agents tested, only hydroxyurea showed marked collateral hypersensitivity in NYH/TPT cells.     

A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer

PURPOSE: Topotecan (Hycamtin is active in small-cell lung cancer (SCLC). This phase II study investigated the efficacy and safety of topotecan in combination with either cisplatin or etoposide in untreated extensive disease SCLC (ED SCLC). PATIENTS AND METHODS: Patients with untreated ED SCLC were randomised to treatment with T/C (topotecan 1.25mg/(m(2)day) IV days 1-5, cisplatin 50mg/m(2) IV day 5; 41 patients) or T/E (topotecan 0.75 mg/(m(2)day) IV days 1-- 5, etoposide 60 mg/(m(2)day) IV days 1-5; 41 patients) every 21 days. Response was evaluated by strict radiological criteria. RESULTS: Response rates were similar for T/C (63.4%, 95% CI: 48.7-78.2%) and T/E (61.0%, 95% CI: 46-76%) with one patient in each arm who underwent complete response. Median survival was 41.6 weeks (9.6 months) for the T/C group and 43.7 weeks (10.1 months) for the T/E group. Toxicity was primarily haematological in both groups. The proportion of patients with grades 3-4 anaemia was significantly higher in the T/C arm (46.4%) versus 20% with the T/E arm (p=0.018). The proportion of patients with grade 4 neutropenia was not significantly lower with T/C (56.1%) than with T/E (65.0%, p=0.41), as was the incidence of associated events such as sepsis (T/C: 0%; T/E: 9.8%, p=0.11). The overall deliverability of either regimen was similar. The most frequent non-haematological adverse experiences of all grades per patient were nausea (T/C: 43.9%; T/E: 36.6%), and alopecia (T/C: 39.0%; T/E: 56.1%). Topotecan did not appear to increase the frequency of adverse events specifically associated with cisplatin. CONCLUSION: This study showed T/C and T/E to be effective and well tolerated in patients with ED SCLC and further evaluation of topotecan in first line SCLC is warranted.     

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.     

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.