A phase II study of 9-aminocamptothecin in advanced non-small-cell lung cancer.
A phase II study of 9-aminocamptothecin in advanced non-small-cell lung cancer.
复制标题
9-氨基喜树碱治疗晚期非小细胞肺癌的 II 期研究。
DOI：
10.1023/a:1008432729754
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Golomb,HM
中科院分区：
文献类型：
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作者：
Vokes,EE;Ansari,RH;Masters,GA;Hoffman,PC;Klepsch,A;Ratain,MJ;Sciortino,DF;Lad,TE;Krauss,S;Fishkin,PA;Golomb,HM
9- aminocamptothecin （9-AC）是喜树碱的合成类似物。I期研究确定最大耐受剂量为1416 μg/m2/day × 3，连续静脉输注（CVI）伴剂量限制性中性粒细胞减少症。患者和方法符合条件的患者为IIIB或IV期非小细胞肺癌（NSCLC），疾病可测量。患者最初接受1416 μg/m2/d × 3 CVI治疗，随后给予粒细胞集落刺激因子（G-CSF）支持。治疗13例后，剂量降至1100 μg/m2/d。每14天重复一个周期，直到肿瘤进展。结果治疗组58例，1416 μg/m2/d组13例，1100 μg/m2/d组45例。50%为腺癌，17%为鳞状细胞癌。71%的人患有第四期疾病。5例患者出现部分缓解（缓解持续时间9-28周），总缓解率为8.6%（95%置信区间（CI）： 2.9%-19%）。中位进展时间为2.3个月，整个研究人群的中位生存期为5.4个月，一年生存率为30%。27例接受二线化疗的患者一年生存率为56.7%。1416 μg/m2/d时，13例患者中分别有6例和5例出现4级中性粒细胞减少症和血小板减少症；当剂量为1100 μg/m2/d时，45例患者中分别有12例和3例出现上述毒性。结论9- ac在未治疗的非小细胞肺癌中具有适度的单药活性。在本研究中使用的剂量和时间表似乎没有进一步的评估。探索更长的给药时间表是有必要的。
Background9-Aminocamptothecin (9-AC) is a synthetic analogue of camptothecin. Phase I studies, identified the maximum tolerated dose as 1416 μg/m2/day × 3 as continuous intravenous infusion (CVI) with dose-limiting neutropenia.Patients and methodsEligible patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) with measurable disease. Patients were initially treated at 1416 μg/m2/d × 3 by CVI followed by granulocyte-colony stimulating factor (G-CSF) support. This dose was decreased to 1100 μg/m2/d after the first 13 patients. Cycles were repeated every 14 days until tumor progression.ResultsFifty-eight patients were treated, thirteen at 1416 μg/m2/d and 45 at 1100 μg/m2/d. Fifty percent had adenocarcinoma and 17% squamous cell carcinoma. Seventy-one percent had stage IV disease. Five patients had a partial response (response duration 9–28 weeks) for an overall response rate of 8.6%, (95% confidence intervals (CI): 2.9%–19%). Median time to progression was 2.3 months and the median survival for the entire study population 5.4 months with a one-year survival rate of 30%. The one-year survival rate for 27 patients who received second line chemotherapy was 56.7%. Toxicities at 1416 μg/m2/d included grade 4 neutropenia and thrombocytopenia in six and five of 13 patients, respectively; at 1100 μg/m2/d these toxicities were observed in 12 and three of 45 patients, respectively.Conclusion9-AC has modest single-agent activity in previously untreated NSCLC. Its further evaluation at the dose and schedule employed in this study does not seem indicated. Exploration of more prolonged administration schedules may be warranted.