Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer.
Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer.
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DOI：
10.1097/jto.0b013e31824abca2
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Dowlati A
中科院分区：
文献类型：
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作者：
Schwandt A;Mekhail T;Halmos B;O'Brien T;Ma PC;Fu P;Ivy P;Dowlati A
复发性小细胞肺癌(SCLC)预后很差。拓扑异构酶I和II的抑制剂和DNA损伤剂被认为是最有效的抗小细胞肺癌药物。雷贝卡霉素类似物(RA，Becatacarin)是一种抗肿瘤抗生素，对拓扑异构酶I和II都有抑制活性，并具有DNA嵌入特性。我们对复发、敏感的小细胞肺癌患者进行了RA的II期试验，主要终点为应答率。既往治疗的小细胞肺癌患者在一线化疗完成后复发超过60天的患者接受RA静脉注射治疗。剂量为140 mg/m2，共21天，第1~5天，最多6个周期。符合条件包括脑电地形图评分0-2和适当的器官功能。采用两阶段设计。纳入了20名可评估的患者。中位年龄61岁。2名患者(10%)有部分反应，6名患者病情稳定。临床受益率为40%(95%可信区间23~%)。中位无进展生存期为2个月(95%可信区间1.2~5.2个月)。中位生存期为6.7个月(95%可信区间：3.3~8.0个月)。没有发生与治疗相关的死亡。4级中性粒细胞减少症和血小板减少症的发生率分别为23%和14%。总而言之，RA在复发、敏感的小细胞肺癌中具有单药活性，毒性可控，但与现有的治疗这种疾病的药物相比不太可能提供任何优势。
Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Toposiomerase I and II inhibitors and DNA damaging agents are considered amongst the most active agents against SCLC. Rebeccamaycin analogue (RA, Becatacarin) is an anti-tumor antibiotic with inhibitory activity against both topoisomerase I and II as well as DNA intercalating properties. We performed a phase II trial of RA in relapsed, sensitive SCLC with the primary endpoint of response rate. Patients with previously treated SCLC who relapsed more than 60 days after completion of first-line chemotherapy were treated with RA administered i.v. at a dose of 140 mg/m2 on days 1–5 of 21 day cycles for a maximum of 6 cycles. Eligibility included ECOG PS 0–2 and adequate organ function. A 2-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two (10%) patients had a partial response and six had stable disease. The clinical benefit rate (CBR) was 40% (95% CI 23–64%). The median progression free survival was 2 months (95% CI 1.2–5.2 mo). The median survival was 6.7 months (95% CI: 3.3–8.0 months). No treatment-related deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 23% and 14% of patients respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.