Phase II Trial of OGX-011 in Combination with Docetaxel in Metastatic Breast Cancer
Phase II Trial of OGX-011 in Combination with Docetaxel in Metastatic Breast Cancer
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DOI：
10.1158/1078-0432.ccr-08-1159
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发表时间：
2009-01-15
影响因子：
11.5
通讯作者：
Eisenhauer, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Chia, Stephen;Dent, Susan;Eisenhauer, Elizabeth A.
目的：簇蛋白是一种响应细胞应激而激活的抗凋亡蛋白。 OGX-011是第二代反义寡核苷酸，可抑制凝聚素表达。这项11期试验的主要目的是评估OGX-011和多西紫杉醇联合治疗转移性乳腺癌的安全性和有效性。实验设计：患有可测量转移性乳腺癌的女性和前14名患者中的6名需要继续进行第二阶段试验。结果：15名患者入组。平均交付六个周期（范围，2-10）。确认有 5 名部分缓解，缓解率为 33%（95% 置信区间，11.8-61.6%），另外 9 名（60%）患者病情稳定。疾病稳定的中位持续时间为 9.3 个月。中位进展时间为 8 个月（95% 置信区间，5.62-9.43 个月）。毒性作用与单药多西他赛相似。尽管治疗时血清簇蛋白下降，但未观察到下降幅度与缓解之间存在相关性。结论：OGX-011 与多西紫杉醇 75 mg/m(2) 的组合耐受性良好，在这些转移性乳腺癌患者中观察到临床活性，但缓解数量不足以满足进入第二阶段累积的标准。
Purpose: Clusterin is an antiapoptotic protein activated in response to cellular stress. OGX-011 is a second-generation antisense oligonucleotide that inhibits clusterin expression. The primary objective of this phase 11 trial was to assess the safety and efficacy of the combination of OGX-011 and docetaxel for metastatic breast cancer.Experimental Design: Women with measurable metastatic breast cancer and = 6 of the first 14 patients was required for the trial to continue to the second stage.Results: Fifteen patients were enrolled. A median of six cycles were delivered (range, 2-10). Five partial responses were confirmed for a 33% response rate (95% confidence interval, 11.8-61.6%) with a further 9 (60%) patients showing stable disease. The median duration of stable disease was 9.3 months. The median time to progression was 8 months (95% confidence interval, 5.62-9.43 months). Toxic effects were similar to those with single agent docetaxel. Although serum clusterin decreased on treatment, there was no relationship observed between the magnitude of decrease and response.Conclusion: The combination of OGX-011 and docetaxel at 75 mg/m(2) is well tolerated and clinical activity was seen in these patients with metastatic breast cancer, but there was an insufficient number of responses to meet the criteria for proceeding to the second stage of accrual.