Small E J, McMillan A, Meyer M, Chen L, Slichenmyer W J, Lenehan P F, Eisenberger M
University of California, San Francisco, CA, USA.
J Clin Oncol. 2001 Mar 1;19(5):1304-11. doi: 10.1200/JCO.2001.19.5.1304.
Validated end points are lacking for clinical trials in hormone-refractory prostate cancer (HRPC). Controversy remains regarding the utility of a posttreatment decline of prostate-specific antigen (PSA). The purpose of this study was to determine whether posttreatment declines in PSA were associated with clinical measures of improvement in a randomized phase III trial of suramin plus hydrocortisone versus placebo plus hydrocortisone.
A total of 460 HRPC patients were randomized to receive suramin plus hydrocortisone (n = 229) or placebo plus hydrocortisone (n = 231). All patients had symptomatic, metastatic HRPC requiring opioid analgesics. Clinical end points evaluated included overall survival, objective progression-free survival (OPFS), and time to pain progression (TTPP). An evaluation of overall survival, OPFS, and TTPP as a function of a PSA decline of > or = 50%, lasting at least 28 days, was undertaken by using a landmark analysis at 6, 9, and 12 weeks. A multivariate analysis of the impact of PSA decline was performed on these clinical end points.
A decline in PSA of > or = 50% lasting > or = 28 days was significantly associated with a prolonged median overall survival, OPFS, and TTPP, both in the entire group and the suramin plus hydrocortisone group at all three landmarks in both univariate and multivariate analysis.
In this prospective, randomized trial of suramin plus hydrocortisone versus placebo plus hydrocortisone, a posttherapy decline in PSA of > or = 50%, lasting 28 days, was associated with prolonged median overall survival, improved median progression-free survival, and median TTPP. This analysis suggests that a posttreatment decline in PSA may be a reasonable intermediate end point in HRPC trials and calls into question the clinical utility of preclinical assays evaluating the in vitro effect of given agents on PSA secretion.
激素难治性前列腺癌（HRPC）临床试验缺乏经过验证的终点指标。前列腺特异性抗原（PSA）治疗后下降的效用仍存在争议。本研究的目的是在一项苏拉明加氢皮质激素与安慰剂加氢皮质激素的随机III期试验中，确定PSA治疗后下降是否与改善的临床指标相关。
总共460例HRPC患者被随机分为接受苏拉明加氢皮质激素（n = 229）或安慰剂加氢皮质激素（n = 231）。所有患者均患有需要阿片类镇痛药的有症状的转移性HRPC。评估的临床终点包括总生存期、客观无进展生存期（OPFS）和疼痛进展时间（TTPP）。通过在6、9和12周时进行标志性分析，评估总生存期、OPFS和TTPP作为PSA下降≥50%且持续至少28天的函数。对这些临床终点进行了PSA下降影响的多变量分析。
在整个组以及苏拉明加氢皮质激素组中，在所有三个标志性时间点的单变量和多变量分析中，PSA下降≥50%且持续≥28天均与中位总生存期、OPFS和TTPP延长显著相关。
在这项苏拉明加氢皮质激素与安慰剂加氢皮质激素的前瞻性随机试验中，PSA治疗后下降≥50%且持续28天与中位总生存期延长、中位无进展生存期改善和中位TTPP相关。该分析表明，PSA治疗后下降可能是HRPC试验中一个合理的中间终点，并对评估给定药物体外对PSA分泌影响的临床前试验的临床效用提出质疑。
