Department of Respiratory Medicine, NHO Shikoku Cancer Center, Matsuyama, Japan.
Lung Cancer. 2011 Oct;74(1):80-4. doi: 10.1016/j.lungcan.2011.01.018. Epub 2011 Feb 18.
Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients.
Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases.
Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths.
This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC.
化疗是广泛期小细胞肺癌（ED-SCLC）治疗的主要手段，尽管生存获益仍然有限。我们在化疗初治和复发性 SCLC 患者中进行了氨柔比星（拓扑异构酶 II 抑制剂）和拓扑替康（拓扑异构酶 I 抑制剂）的 II 期临床试验。
氨柔比星（35mg/m2）和拓扑替康（0.75mg/m2）分别在第 3-5 天和第 1-5 天给药。客观缓解率（ORR）被设定为主要终点，在化疗初治和复发性病例中分别进行评估。
共纳入 59 例患者（化疗初治 31 例，复发性 28 例）。化疗初治和复发性病例的 ORR 分别为 74%和 43%。生存数据也很有希望，化疗初治和复发性病例的中位无进展生存期和中位总生存期分别为 5.3 个月和 14.9 个月，4.7 个月和 10.2 个月。甚至难治性复发性病例对治疗也有较好的反应（27%的 ORR）。主要毒性为骨髓抑制，97%的患者出现 3 或 4 级中性粒细胞减少症，导致 41%的患者出现 3 或 4 级发热性中性粒细胞减少症和 2 例毒性死亡。
这项 II 期研究表明，拓扑替康和氨柔比星两药联合治疗 ED-SCLC 尤其是复发性患者具有良好的疗效和中等的安全性。
