Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer
Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer
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DOI：
10.1200/jco.2006.08.3998
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发表时间：
2007-05-20
影响因子：
45.3
通讯作者：
Ross, Graham
中科院分区：
文献类型：
--
作者：
Eckardt, John R.;von Pawel, Joachim;Ross, Graham
目的单药静脉注射拓扑替康是治疗一线化疗失败的小细胞肺癌的有效方法。这项开放的、随机的第三阶段研究比较了口服拓扑替康和静脉拓扑替康在对初始化疗敏感的小细胞肺癌患者中的作用。患者和方法将对一线治疗有完全或部分反应、东部合作肿瘤组表现状态：52、可测量的复发疾病(WHO标准)且免治疗间隔为90天的局限性或广泛性小细胞肺癌患者分配到口服拓扑替康2.3 mg/m(2)/d，第1至第5天，或静脉注射拓扑替康1.5 mg/m(2)/d，第1至第5天，每21天一次。主要终点是由盲目治疗的外部评价者确认的应答率。在意向处理分析中，口服拓扑替康(n=153)有效率为18.3%，静脉注射拓扑替康(n=151)有效率为21.9%，两者差别(口服-IV)为-3.6%(95%CI，-12.6%~5.5%)。口服和静脉注射拓扑替康的中位生存期分别为33.0周和35.0周，1年和2年生存率分别为32.6%和12.4%，29.2%和7.1%。两组的三线化疗相似(口服33%，静脉注射35%)。口服和静脉注射拓扑替康的患者4级毒性发生率分别为：中性粒细胞减少47%和%，血小板减少29%和18%，3级或4级贫血23%和31%，败血症3%和3%。最常见的非血液学不良反应(所有级别)包括恶心(43%口服；42%IV)、脱发(26%口服；30%IV)、疲乏(31%口服；36%IV)和腹泻(36%口服；20%IV)。结论口服拓朴替康对化疗敏感的小细胞肺癌患者具有与静脉拓朴替康相似的活性和耐受性，为患者提供了一种方便的静脉治疗替代疗法。
PurposeSingle-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.Patients and MethodsPatients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status :5 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of ! 90 days were assigned to treatment with either oral topotecan 2.3 mg/m(2) /d on days 1 through 5 or IV topotecan 1.5 mg/m(2) /d on days I through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.ResultsA total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral - IV) of -3.6% (95% Cl, -12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).ConclusionOral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.