拓扑替康联合顺铂与足叶乙甙联合卡铂一线治疗小细胞肺癌的随机临床研究

A randomized study comparing topotecan plus cisplatin versus etoposide plus carboplatin for previously untreated small cell lung cancer

背景与目的 拓扑替康是治疗复发性小细胞肺癌的有效药物之一，已有的研究结果显示其一线治疗小细胞肺癌也是有效的。本研究拟比较国产拓扑替康联合顺铂（TP）方案与足叶乙甙联合卡铂（CE）方案一线治疗小细胞肺癌的疗效、毒副反应及生存率。方法 细胞学或病理确诊的64例初治小细胞肺癌患者随机分为TP组与CE组，两组各32例患者。TP组：拓扑替康0．75mg／（m^2·d），静脉滴注30min，第1～5天，顺铂25mg／（m^2·d），静点并水化，第1～3天。CE组：卡铂300mg／m^2，静脉滴注，第1天，足叶乙甙100mg／d，静脉滴注，第1～5天。两种方案均为21天重复。完成2周期化疗的患者进行疗效、毒副反应评价，并分析生存情况。局限期患者化疗结束后接受胸部放疗或手术。结果 TP组总有效率为75．0％，中位生存期为10．5个月，1、2、3年生存率分别为40．6％、18．8％、9．4％；CE组总有效率为68．8％，中位生存期为9．6个月，1、2、3年生存率分别为34．4％、15．6％、9．4％。两组的总有效率、中位生存期及1、2、3年生存率差异均无显著性统计学意义（P〉0．05）。两组毒副反应均以骨髓抑制、恶心呕吐、脱发等为主，Ⅲ度和Ⅳ度毒副反应差异无显著性统计学意义（P〉0．05）。结论 拓扑替康联合顺铂方案与足叶乙甙联合卡铂方案相比，疗效与生存相似，毒副反应可耐受，是一线治疗小细胞肺癌的有效方案。

Background and objective Topotecan is one of active agents for relapsed small cell lung cancer （SCLC）, some studies have shown that it is effective against SCLC as the first-line drug. This study is to assess the efficacy, toxicity and survival rate of topotecan plus cisplatin （TP） versus etoposide plus carboplatin （CE） in patients with previously untreated SCLC. Methods Sixty-four patients with previously untreated SCLC were randomly assigned to receive either TP or CE. Topotecan 0.75 mg/（m^2· d） via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/（m^2 ·d） on days 1 to 3 with hydration were given to patients in TP group. Carboplatin 300 mg/m^2 on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group. Treatment was repeated every 21 days. Responses and toxicities were evaluated in patients who received two cycles of chemotherapy. Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy. Results Overall response rate was 75.0% in TP group and 68.8% in CE group. The median survival time was 10.5 months in TP group and 9.6 months in CE group. 1-, 2- and 3-year survival rate were 40.6%, 18.8% and 9.4% in TP group and 34.4%, 15.6% and 9.4% in CE group respectively. There were no significant differences in response rate, median survival time and survival rate between two groups （P〉0.05）. Myelosuppression, nausea and vomiting, and alopecia were the most common toxicities, there was no significant difference in grade Ⅲ and Ⅳ toxicities between two groups （P〉0. 05）. Conclusion TP has similar response rate and survivals with CE, and its toxicities are acceptable. TP regimen is an effective first-line treatment for SCLC.