Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the prostate cancer clinical trials working group
Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the prostate cancer clinical trials working group
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DOI：
10.1200/jco.2007.12.4487
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发表时间：
2008-03-01
影响因子：
45.3
通讯作者：
Hussain, Maha
中科院分区：
文献类型：
--
作者：
Scher, Howard I.;Halabi, Susan;Hussain, Maha
PurposeTo更新的资格和结果措施的试验，评估系统治疗患者进行性前列腺癌和去势水平的testosterone.MethodsA委员会的研究人员进行试验经验丰富的前列腺癌定义新的共识标准，通过审查以前的标准，反应评价标准在实体瘤（RECIST），结果前列腺癌临床试验工作组（PCWG 2）推荐了一个双目标范例：（1）控制、缓解或消除治疗开始时存在的疾病表现，以及（2）预防或延迟预期发生的疾病表现。前列腺癌的进展，尽管去势水平的睾酮被认为是去势抵抗，而不是激素难治性。使用标准疾病评估来确定合格性，以验证疾病进展、既往治疗、不同的临床亚型和预测模型。独立报告前列腺特异性抗原（PSA）、影像学和临床指标的结局，避免分组分类，如完全或部分缓解。在大多数试验中，如果没有其他疾病进展的证据，PSA和/或疼痛的早期变化不会采取行动，治疗应持续至少12周，以确保足够的药物暴露。骨扫描报告为“新病灶”或“无新病灶”，软组织疾病的变化通过RECIST评估，疼痛使用经验证的量表。定义预防/延迟终点的合格性需要注意估计的事件频率和/或随机分配到对照组。结论PCWG 2建议在从II期到III期试验的过程中，越来越重视时间至事件终点（即，进展失败）作为决策辅助。随着中间终点预测临床获益效用的数据生成，建议将不断发展。
PurposeTo update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone.MethodsA committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data.ResultsThe Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or " no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group.ConclusionPCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.