卡铂联合足叶乙甙治疗小细胞肺癌40例回顾分析

目的探讨卡铂、足叶乙甙联合（CE方案）治疗小细胞肺癌的疗效及不良反应。方法收集法国波尔多大学医院呼吸科1996年1月至2003年12月收治的40例接受CE方案化疗的小细胞肺癌患者完整的病例资料，分析CE方案化疗的有效率、不良反应和患者的生存期。结果40例中，局限期（LD）15例，广泛期（ED）25例。化疗总有效率为60．0％．LD和ED的OR分别为73．3％和52．0％，中位无进展生存期分别为5．9个月和5．6个月，中住生存期分别为7．2个月和6．8个月，1年生存率分别为26．7％和16．0％。3—4度粒细胞减少、贫血、恶心呕吐发生率分别为55．0％，15．0％，17．5％。结论CE方案治疗小细胞肺癌疗效满意，患者耐受性好。     

小细胞肺癌骨髓转移29例临床分析

目的探讨小细胞肺癌(SCLC)骨髓转移的临床特征、治疗方法及预后影响因素。方法回顾性分析29例SCLC骨髓转移病例的临床资料,应用SPSS10.0软件包分析其预后影响因素。结果29例SCLC患者中位年龄为52岁。诊断为局限期(LD)11例,广泛期(ED)18例。出现临床症状到确诊为SCLC的中位时间是2个月,诊断SCLC后到确诊骨髓转移的中位时间是20天。全组患者中位生存期为6个月(2～19个月),确诊骨髓转移后中位生存期为5个月(10天～18个月)。患者生存期与临床分期、发病部位、转移部位数目、含铂类化疗方案及骨髓缓解无关。采用含足叶乙甙(VP16)的化疗方案、联合放疗与患者生存期密切相关。结论SCLC骨髓转移后生存期短,治疗仍以化疗为主的综合治疗。采用含VP16的化疗方案、联合放疗对SCLC骨髓转移的预后较好。     

TEP方案治疗小细胞肺癌21例临床分析

探讨拓扑替康 (topotecan ,TPT)联合依托泊苷 (etoposide ,Vp 16)、顺铂 (cisplatin ,DDP)组成的TEP方案治疗小细胞肺癌 (small celllungcancer ,SCLC)的临床疗效。 2 1例初治SCLC患者接受治疗 ,Vp 1670mg/ (m2 ·d) ,连用 5d ;TPT0 7mg/ (m2 ·d) ,于Vp 16后 1h应用 ,静脉滴入 3 0min ,连用 5d ;DDP 80mg/m2 ,分 3d静脉滴入。 2 1d为 1个周期 ,至少化疗 2个周期。 2 1例患者均可评价疗效。其中CR 8例 ,PR 8例 ,有效率 (RR)为 76 2 % ( 16/ 2 1) ,局限期 (LD)RR为90 0 % ( 9/ 10 ) ,广泛期 (ED)RR为 63 6% ( 7/ 11) ,其中 4例脑转移者PR 1例 ,SD 1例 ;全组患者中位生存期 11 5个月 ,1、2年生存率分别为 42 9% ( 9/ 2 1)和 19 0 % ( 4 / 2 1) ;2 1例患者均可评价不良反应 ,主要不良反应为骨髓抑制 ,Ⅲ～Ⅳ度白细胞减少的发生率 76 2 % ( 16/ 2 1) ,血小板减少的发生率为 61 9% ( 13 / 2 1) ,非血液学毒性主要为恶心、呕吐、脱发、乏力、肝肾功能异常等。TEP方案疗效肯定 ,能改善SCLC的生存期及生存率 ,可作为SCLC的一线治疗方案 ;主要不良反应为骨髓抑制 ,非血液学毒性轻微     

CODE方案密集周化疗和多学科综合治疗小细胞肺癌

目的探讨CODE方案密集周化疗及多学科综合治疗小细胞肺癌(small cell lung cancer,SCLC)的疗效及生存预后因素。方法 1995年3月至2005年12月入组SCLC患者118例,其中男性86例(72.9%),女性32例(27.1%),中位年龄55岁,局限期(LD)30例(25.4%),广泛期(ED)88例(74.6%),所有患者均有病理或细胞学诊断。周化疗药物包括顺铂、长春新碱、阿霉素及依托泊苷,主要通过增加给药频率增加药物剂量强度,总疗程为9周。CODE方案疗效达CR或PR即可接受胸部放疗(RT),放疗后患者KPS60,再行维持治疗(MCT)。11例患者于CODE前或后进行了手术。对CODE及综合治疗均按实体瘤疗效评定。应用Kaplan-Meier法绘制生存曲线,寿命表法计算生存率,COX多因素回归比例风险模型进行了生存预后因素分析。结果对110例患者进行了CODE疗效评定,其中CR 17例(15.5%),PR 79例(71.8%),PD 5例(4.5%),不良反应轻微。主要治疗模式是CODE+RT+MCT,总计83例(70%)。105例(89%)患者对CODE+多学科治疗有效,CR 29例(25%),PR76例(64%)。118例SCLC患者的中位生存期(MST)为21个月(95%CI:17.5～24.6),ED为17个月(95%CI:12.4～21.6),LD 38个月(95%CI:12.2～63.8),P=0.000。ED、LD 1年生存率分别为70.5%和93.3%(P=0.022),5年生存率为12.5%和40%(P=0.003)。单因素及COX多因素分析显示疗效、治疗模式及疾病分期与患者生存密切相关。结论 SCLC患者经CODE及多学科综合治疗生存明显延长。CODE方案是SCLC重要的内科治疗,且耐受性好。早期的SCLC可选择外科治疗。维持治疗的临床研究值得进一步探讨。     

TEP方案治疗小细胞肺癌的临床研究

目的 :探讨拓扑替康 (topotecan ,TPT )联合依托泊苷 (etoposide ,Vp -16)、顺铂 (cisplatin ,DDP)组成的TEP方案治疗小细胞肺癌的临床疗效、生存期和耐受性。方法 :45例初治SCLC患者 ,其中TEP方案治疗组 2 1例 ,EP方案对照组 2 4例。结果 :TEP组CR 8例 ,PR 8例 ,有效率 (RR)为 76.2 % ,局限期 (LD)者RR为 90 .0 % ,广泛期 (ED)者RR为 63 .6% ,其中 4例脑转移者PR 1例。EP组中CR 7例 ,PR 9例 ,RR为 66.7% ,LD者RR为 81.8% ,ED者RR为 53 .8% ,其中 5例脑转移者未见CR、PR者。两组有效率比较无显著性差异 (P >0 .0 5)。TEP组中位生存期 11.5个月 ,一、二年生存率分别为 42 .9%和 19.0 % ;EP组中位生存期 8.5个月 ,一、二年生存率分别为3 7.5%和 8.3 % ,两组生存期比较 ,差异具有显著性 (P <0 .0 5)。两组主要不良反应为骨髓抑制 ,TEP组Ⅲ～Ⅳ度白细胞减少的发生率 76.2 % (16/ 2 1)明显高于EP组 3 7.5% (9/ 2 4) ,具有统计学意义 (P <0 .0 5) ;两组血小板减少的发生率分别为 61.9%和 3 3 .3 % ,差异显著 (P <0 .0 5)。结论 :TEP方案治疗SCLC疗效肯定 ,可能具有治疗和预防脑转移的作用 ,其生存期及生存率较EP方案均有改善 ,可作为SCLC的一线治疗应用 ;主要不良反应为骨髓抑制 ,临床应用时应予重视     

TCF方案与PF方案治疗晚期食管癌的临床研究

目的:观察比较紫杉醇联合顺铂、氟尿嘧啶(TCF方案)与顺铂加氟尿嘧啶(PF方案)两个方案治疗晚期食管癌的临床疗效和毒性反应。方法:共69例患者,分别用TCF、PF方案化疗,28天为1个周期。2个周期以后按照WHO标准进行疗效评价。结果:TCF方案可评价疗效者32例,CR2例,PR15例,有效率53.1%。中位疾病进展时间为5.4个月,中位生存时间10.1个月。可评价毒副反应33例。主要不良反应为脱发、中性粒细胞降低,恶心、呕吐也较常见。PF方案可评价疗效者29例,PR14例,有效率48.3%。中位疾病进展时间3.9个月,中位生存期8.7个月。主要不良反应为恶心、呕吐。结论:TCF方案对晚期食管癌疗效好,毒副反应可耐受,可以考虑作为治疗晚期食管癌的主要治疗方案。     

TP与GP方案治疗晚期非小细胞肺癌的随机对照临床研究

目的:紫杉醇(paclitaxel,TAX)和吉西他滨(gemcitabine,GEM)是目前治疗肺癌的一线药物。本研究对这二药联合DDP的TP与GP方案治疗晚期NSCLC的近期疗效及不良反应进行对比。方法:采用前瞻性开放性随机对照临床研究方法,对56例入组患者随机采用TP(TAX、DDP)或GP(GEM、DDP)方案化疗,化疗至少2周期后评价疗效及不良反应。结果:TP组、GP组有效率分别是39.1%(9/23)和40.0%(8/20);中位生存期分别为8.8、9.2个月,无病生存期分别为3.6、3.7个月;1年生存率分别为32.3%和31.0%;各组间差异均无显著性。主要不良反应是Ⅲ-Ⅳ度骨髓抑制、恶心呕吐、乏力和静脉炎。GP组的白细胞减少(42.2%)、中性粒细胞减少(36.2%)发生率最低,血小板减少发生率(53.0%)最高,与TP组(71.0%、57.0%、13.0%)比较差异均具有显著性(P<0.01);GP组、TP组的恶心呕吐发生率分别为16.8%、25.8%;GP组的乏力症状发生率组(38.5%),显著高于TP组(P<0.01)。结论:TP和GP方案治疗晚期NSCLC近期疗效差异无显著性。     

替莫唑胺化疗方案联合全脑放疗治疗非免疫功能缺陷PCNSL的临床观察

目的研究替莫唑胺化疗方案联合全脑放疗治疗非免疫功能缺陷PCNSL的临床效果。方法回顾性分析应用替莫唑胺化疗方案联合全脑放疗治疗的168例非免疫功能缺陷PCNSL患者的基本资料、临床表现、化疗周期、化疗疗效、不良反应、生存分析、随访时间等数据信息,研究了替莫唑胺化疗方案联合全脑放疗治疗非免疫功能缺陷PCNSL患者的临床疗效。结果 168例患者治疗后随访时间为0~24个月;平均生存期为(11.8±2.3)个月。CR 51例(30.35%)、PR 63例(37.50%)、SD 23例(13.69%)、PD 31例(18.45%)、有效率67.86%以及临床控制率81.55%。不良反应主要有:贫血、骨髓抑制、疲劳、恶心呕吐等。结论替莫唑胺化疗方案联合全脑放疗治疗能够比较有效地提高患者生存率,值得临床推广应用。     

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。     

FOLFIRI方案二线治疗复发或转移性结直肠癌

目的 探讨FOLFIRI方案(伊立替康+5-氟尿嘧啶+醛氢叶酸)用于奥沙利铂治疗失败的复发或转移性结直肠癌的临床疗效和安全性.方法 为前瞻性、单组开放式、多中心临床研究.一线化疗失败的结直肠癌患者66例,接受FOLFIRI方案化疗,直至病情进展或不良反应不能耐受.每3个周期评价疗效,并观察不良反应.结果 61例患者可评价客观疗效,客观有效率为16.4%,疾病控制率为73.8%.59例患者随访资料完整,中位疾病进展时间(TTP)为5.0个月,中位至死亡时间(TTD)为9.9个月,中位生存时间为18.2个月.不良反应以中性粒细胞减少、恶心呕吐、急性胆碱能综合征、脱发、迟发性腹泻最常见.3和4度中性粒细胞减少的发生率为22.7%.结论 FOLFIRI方案二线治疗奥沙利铂化疗失败的晚期结直肠癌,有较高的肿瘤控制率,患者耐受性好,并可以延长患者的总生存期.     

A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer.

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.     

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.     

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report

Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC).Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning.Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC.Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC.Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR >2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.     

Alternating chemotherapy with cyclophosphamide/adriamycin/vincristine (CAV) and cisplatin/etoposide (PVP) against small cell lung cancer. Eastern Shikoku Lung Cancer Chemotherapy Group.

Seventy-four confirmed small cell lung cancer (SCLC) patients received alternating combination chemotherapy with CAV and PVP. The CAV comprised of cyclophosphamide 800 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1 and vincristine 1.4 mg/m2 on day 1, administered every 3-4 weeks. The PVP comprised cisplatin 80 mg/m2 on day 1 and etoposide 75 mg/m2 on day 1-5 administered every 3-4 weeks. Of these 74 patients, 63 (85.1%) achieved complete or partial responses with 16 (21.6%) obtaining a complete response. The median survival time was 13.2 months: 10.4 months in patients with extensive disease (ED), 16.3 months in those with limited disease (LD). A three-year disease-free period was achieved in eight patients (11.2%: 4.8% with ED, 16.8% with LD). The median duration of response was 28.3 weeks: 20.1 weeks with ED and 44.0 weeks with LD. The most commonly encountered side effects were nausea, vomiting, alopecia and myelosuppression but all were tolerable. We consider CAV-PVP to be an effective combination regimen for treating SCLC.     

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.     

Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.

A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin''s carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.     

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.     

A phase II study of biweekly irinotecan and cisplatin for patients with extensive stage disease small cell lung cancer

BACKGROUND: An irinotecan and cisplatin (IP) combination is one of active regimen used in treatment of extensive stage disease (ED) small cell lung cancer (SCLC). However, a 4-week cycle of irinotecan treatment can result in significant myelosuppression and diarrhea. Therefore, the present study was conducted to evaluate the efficacy and safety of biweekly IP in patients with ED SCLC. METHODS: Patients with previously untreated ED SCLC received intravenous irinotecan at a dose of 60mg/m(2) and cisplatin at a dose of 30mg/m(2) on days 1 and 15 every 4 weeks. RESULTS: Thirty-five patients were enrolled in this study. Three complete responses and 23 partial responses were confirmed, giving an overall response rate of 74.3%. After a median follow-up of 15.1 months, the median time to progression and overall survival were 7.7 months and 12.2 months, respectively. Grade 3/4 neutropenia occurred in seven patients and grade 3 febrile neutropenia was observed in one patient. Grade 3 diarrhea occurred in two patients. CONCLUSIONS: The combination chemotherapy of biweekly IP was found to be well tolerated and effective in patients with ED SCLC. Further evaluation of the combination of IP at the dose and schedule in this study is warranted in ED SCLC patients.     

VP-16 and cisplatin as first-line therapy for small-cell lung cancer

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.     

Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer: a phase II trial of West Japan Thoracic Oncology Group

Irinotecan is a topoisomerase I inhibitor that is highly active against small cell lung cancer (SCLC). Etoposide is another drug that is effective for SCLC. Since combination of these two topoisomerase inhibitors revealed a synergistic effect in vitro and showed a safety in phase I study, we conducted a phase II study in patients with previously un-treated extensive disease (ED) SCLC to evaluate the efficacy and toxicity of this combination. Fifty patients with previously untreated ED-SCLC were enrolled. Irinotecan was administered intravenously at 60mg/m(2) on days 1, 8, and 15, while etoposide was given at 80mg/m(2) on days 2-4. Treatment was repeated every 4 weeks for four cycles. The overall response rate was 66.0%, with a complete response rate of 10.0%. The median survival time was 11.5 months and the 1- and 2-year survival rates were 43.2 and 14.4%, respectively. The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (62.9%), leukopenia (28.0%), and anemia (14%). The other grade 3 toxicity was diarrhea (2%). This irinotecan and etoposide regimen is active against ED-SCLC with relatively mild toxicity.