多西他赛和泼尼松联合或不联合 OGX-011 治疗转移性去势抵抗性前列腺癌的随机 II 期研究。

Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer.

机构信息

British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

出版信息

J Clin Oncol. 2010 Sep 20;28(27):4247-54. doi: 10.1200/JCO.2009.26.8771. Epub 2010 Aug 23.

DOI:10.1200/JCO.2009.26.8771

PMID:20733135

Abstract

PURPOSE

To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer.

PATIENTS AND METHODS

Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin.

RESULTS

Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87).

CONCLUSION

Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.

摘要

目的

评估 OGX-011（一种针对簇集素的反义抑制剂）联合多西他赛/泼尼松在转移性去势抵抗性前列腺癌患者中的临床疗效。

方法

患者按 1:1 比例随机分配至多西他赛/泼尼松联合（A 组）或不联合（B 组）OGX-011（每周静脉滴注 640mg）治疗。主要终点为前列腺特异性抗原（PSA）较基线下降≥50%的患者比例，若 PSA 下降比例超过 60%，则认为试验治疗具有研究意义。次要终点为客观缓解率、无进展生存期（PFS）、总生存期（OS）和血清簇集素的变化。

结果

共纳入 82 例患者，每组 41 例。OGX-011 的不良反应包括寒战和发热。第 1 周期后，A 组血清簇集素中位数下降 26%，B 组升高 0.9%（P<0.001）。A 组 58%的患者 PSA 下降≥50%，B 组为 54%。A 组和 B 组的部分缓解率分别为 19%和 25%。A 组的中位 PFS 和 OS 时间分别为 7.3 个月（95%CI，5.3 至 8.8 个月）和 23.8 个月（95%CI，16.2 个月至不可评估），B 组分别为 6.1 个月（95%CI，3.7 至 8.6 个月）和 16.9 个月（95%CI，12.8 至 25.8 个月）。探索性多因素分析显示，ECOG 体能状态为 0（风险比[HR]，0.27；95%CI，0.14 至 0.51）、仅存在骨或淋巴结转移（HR，0.45；95%CI，0.25 至 0.79）以及接受 OGX-011 治疗（HR，0.50；95%CI，0.29 至 0.87）是 OS 改善的相关因素。