Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16
Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16
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DOI：
10.1093/jnci/djj129
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发表时间：
2006-04-19
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影响因子：
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通讯作者：
Crawford, ED
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文献类型：
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作者：
Petrylak, DP;Ankerst, DP;Crawford, ED
确定可以取代真实结果终点的替代终点对于快速评估新的抗癌药物至关重要。对转移性雄激素非依赖性前列腺癌的II期和III期试验的回顾分析表明，血清前列腺特异性抗原(PSA)水平的下降与生存率之间存在关联。我们使用一项临床试验的数据来评估PSA变化作为潜在的生存替代标记物。方法：将雄激素非依赖性前列腺癌患者随机分为多西紫杉醇/雌激素组(D/E)或米托蒽醌/强的松(M/P)，按西南肿瘤组方案99-16进行治疗。在674名符合条件的患者中，551人接受了基线PSA测量，并在方案的前3个月至少进行了一次PSA测量。用Prentice标准、治疗效果解释比例和变异解释比例三个统计学标准检验PSA水平下降5%~90%和PSA速度在1、2和3个月时是否代孕。所有的统计检验都是双面的。结果：3个月的PSA水平下降了20%-40%，2个月的PSA下降了30%，2个月和3个月的PSA速度满足了所有三个代孕标准。例如，与没有下降的情况相比，3个月PSA下降至少30%与死亡风险降低50%以上相关(危险比[HR]=0.43，95%可信区间[CI]=0.34至0.55；P
The identification of surrogate endpoints that can replace true outcome endpoints is crucial to the rapid evaluation of new cancer drugs. Retrospective analyses of phase II and III trials in metastatic androgen-independent prostate cancer have shown associations between declines in serum prostate-specific antigen (PSA) levels and survival. We evaluated PSA changes as potential surrogate markers for survival by using data from a clinical trial. Methods: Men with androgen-independent prostate cancer were randomly assigned to either docetaxel/estramustine (D/E) or mitoxantrone/ prednisone (M/P) treatment on Southwest Oncology Group Protocol 99-16. Of 674 eligible patients, 551 had a baseline PSA measurement and at least one PSA measurement during the first 3 months on protocol. PSA level declines of 5%-90% and PSA velocity at 1, 2, and 3 months were tested for surrogacy by using three statistical criteria: Prentice's criteria, the proportion of treatment effect explained, and the proportion of variation explained. All statistical tests were two-sided. Results: Three-month PSA level declines of 20%-40%, a 2-month PSA decline of 30%, and PSA velocity at 2 and 3 months met all three surrogacy criteria. For example, a 3-month PSA decline of at least 30% was associated with a more than 50% decrease in the risk of death compared with the lack of such a decline (hazard ratio [HR]= 0.43, 95% confidence interval [CI] = 0.34 to 0.55; P