A Phase I/II Study of GTI-2040 Plus Docetaxel as Second-Line Treatment in Advanced Non-small Cell Lung Cancer A Study of the PMH Phase II Consortium
A Phase I/II Study of GTI-2040 Plus Docetaxel as Second-Line Treatment in Advanced Non-small Cell Lung Cancer A Study of the PMH Phase II Consortium
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DOI：
10.1097/jto.0b013e3181a949b2
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发表时间：
2009-09-01
影响因子：
20.4
通讯作者：
Moore, Malcolm J.
中科院分区：
文献类型：
--
作者：
Leighl, Natasha B.;Laurie, Scott A.;Moore, Malcolm J.
GTI-2040是一种反义寡核苷酸，靶向核糖核苷酸还原酶R2亚基，对DNA合成至关重要。该研究确定了多西他赛加GTI-2040的推荐11期剂量（RP2D）、毒性和晚期非小细胞肺癌（NSCLC）的缓解率。患者和方法：晚期实体瘤患者，最好是铂治疗的非小细胞肺癌，性能状态0 - 2，无中枢神经系统转移症状，器官和骨髓功能充足，并且！在先前的化疗方案中，GTI-2040的剂量逐渐增加，每21天给予14天连续静脉输注（CVI）加多西紫杉醇。结果：共治疗29例，其中非小细胞肺癌24例，激素难治性前列腺癌3例，头颈部癌1例，小细胞肺癌1例。GTI-2040 5 mg/kg作为CVI，连续14天，每21天静脉注射多西他赛75 mg/m(2)作为RP2D。未见剂量限制性毒性。2例RP2D患者出现4/5级发热性中性粒细胞减少症。在1期观察到一个前列腺特异性抗原反应，但在NSCLC患者中没有客观的肿瘤反应。中位进展时间为3.4个月，在RP2D治疗的NSCLC患者为3.2个月。结论：在RP2D， GTI-2040 5 mg/kg/d x 14天，CVI联合多西他赛75 mg/m(2)的活性似乎并不优于多西他赛单独治疗先前治疗的NSCLC。
Introduction: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase 11 dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC).Patients and Methods: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and ! I prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days.Results: Twenty-nine patients were treated, (24 NSCLC, 3 hermone-refractory prostate cancer, I head and neck, and I small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m(2) intravenously every 21 days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase 1, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D.Conclusions: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d x 14 days by CVI plus docetaxel 75 mg/m(2) does not seem superior to docetaxel alone in previously treated NSCLC.