Eckardt John R, von Pawel Joachim, Pujol Jean-Louis, Papai Zsolt, Quoix Elisabeth, Ardizzoni Andrea, Poulin Ruth, Preston Alaknanda J, Dane Graham, Ross Graham
Center for Cancer Care and Research, St Louis, MO 63141, USA.
J Clin Oncol. 2007 May 20;25(15):2086-92. doi: 10.1200/JCO.2006.08.3998.
Single-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 with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status < or = 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of > or = 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.
A 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% CI, -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).
Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
单药静脉注射拓扑替康是一线化疗失败后小细胞肺癌（SCLC）的有效治疗方法。本开放标签、随机、III期研究比较了口服和静脉注射拓扑替康在对初始化疗敏感的SCLC患者中的疗效。
患有局限性或广泛性疾病的SCLC患者，记录显示对一线治疗有完全或部分反应，东部肿瘤协作组体能状态≤2，且有可测量的复发性疾病（WHO标准）且无治疗间隔≥90天，被分配接受以下治疗之一：口服拓扑替康2.3mg/m²/d，第1至5天用药，每21天重复；或静脉注射拓扑替康1.5mg/m²/d，第1至5天用药，每21天重复。主要终点是由对治疗不知情的外部审查员确认的缓解率。
共309例患者被随机分组。在意向性分析中，口服拓扑替康组（n = 153）的缓解率为18.3%，静脉注射拓扑替康组（n = 151）为21.9%，差异（口服-静脉注射）为-3.6%（95%CI，-12.6%至5.5%）。口服拓扑替康的中位生存时间为33.0周，静脉注射拓扑替康为35.0周；口服拓扑替康的1年和2年生存率分别为32.6%和12.4%，静脉注射拓扑替康分别为29.2%和7.1%。两组的三线化疗情况相似（口服组为33%；静脉注射组为35%）。接受口服和静脉注射拓扑替康的患者4级毒性发生率如下：中性粒细胞减少分别为47%和64%，血小板减少分别为29%和18%，3或4级贫血分别为23%和31%，败血症分别为3%和3%。最常见的非血液学不良事件（所有级别）包括恶心（口服组43%；静脉注射组42%）、脱发（口服组26%；静脉注射组30%）、疲劳（口服组31%；静脉注射组36%）和腹泻（口服组36%；静脉注射组20%）。
口服拓扑替康在化疗敏感的SCLC患者中显示出与静脉注射拓扑替康相似的活性和耐受性，为患者提供了一种方便的替代静脉治疗的选择。
