Division of Medical Oncology, Ospedale Giovanni Borea, ASL-1 Imperiese, Via G. Borea 56, I-18038, Sanremo, Imperia, Italy.
Cancer Treat Rev. 2012 Dec;38(8):1020-6. doi: 10.1016/j.ctrv.2012.03.008. Epub 2012 Apr 12.
Prostate cancer is the most common cancer in men. Overall survival is considered the best endpoint for clinical trials, but it is difficult to use in phase-2 studies. Although the reduction of PSA after cytotoxic chemotherapy has been identified as a valid surrogate for overall survival, it has not proven reliable for the evaluation of many biologics. Moreover, the PSA progression-free survival at 3 months was validated only for cytotoxic drugs, and the various measures of progression/delay have not been confirmed by large studies. Ultimately, outside of overall survival, no measure has been validated as a surrogate endpoint after treatment with targeted therapies and vaccine therapy. The PSA levels have a great variability and, theoretically, the use of measures of cell kinetics and PSA may be the most reliable approach to estimate the behavior of metastatic disease. Some measures of PSA kinetics have been well developed in the clinical castration-resistant prostate cancer, the PSA doubling time and the growth rate constant. The studies about the kinetics of PSA measures are reviewed and discussed. To date, studies that consider the measures of PSA kinetics as surrogate endpoints are still very few. However in the near future, the drug evaluation can not proceed separately, with distinct endpoints between cytotoxic and non-cytotoxic agents. Therefore, extensive analysis and validation of measures of kinetics derived from PSA, and candidates for a role for surrogate endpoint, will be needed in phase-3 studies, in order to test their effectiveness in different disease scenarios.
前列腺癌是男性最常见的癌症。总生存期被认为是临床试验的最佳终点，但在 2 期研究中很难使用。虽然细胞毒性化疗后 PSA 降低已被确定为总生存期的有效替代指标，但它在许多生物制剂的评估中并不可靠。此外，3 个月时 PSA 无进展生存期仅在细胞毒性药物中得到验证，各种进展/延迟指标尚未得到大型研究的证实。最终，除了总生存期外，没有任何指标在接受靶向治疗和疫苗治疗后被验证为替代终点。PSA 水平具有很大的可变性，从理论上讲，使用细胞动力学和 PSA 测量可能是估计转移性疾病行为的最可靠方法。一些 PSA 动力学测量方法在临床去势抵抗性前列腺癌中得到了很好的发展，如 PSA 倍增时间和生长率常数。本文回顾和讨论了 PSA 动力学测量的研究。迄今为止，将 PSA 动力学测量作为替代终点的研究仍然很少。然而，在不久的将来，药物评估不能分开进行，细胞毒性和非细胞毒性药物之间有明显的终点。因此，在 3 期研究中需要对来自 PSA 的动力学测量和替代终点候选物进行广泛的分析和验证，以测试它们在不同疾病情况下的有效性。
