Gill Sharlene, Sargent Daniel
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Oncologist. 2006 Jun;11(6):624-9. doi: 10.1634/theoncologist.11-6-624.
The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.
辅助治疗的目的是在根治性切除术后根除微转移残留病灶，以预防或延迟复发。证明新辅助治疗疗效的长期标准是总生存期（OS）的改善。这通常需要进行大样本量、长期随访的III期试验。为了降低完成此类试验的成本和时间，人们对开发替代或替代终点有很大兴趣。替代终点可作为直接评估干预措施对已被接受的临床终点（如死亡率）影响的替代指标。如果明智地使用，替代终点可以加速新疗法的评估，从而更及时地将有效疗法传播给患者。本综述提供了关于无病生存期（DFS）作为OS替代终点的适用性和有效性的观点。讨论了建立替代指标的标准以及在辅助临床试验中使用DFS作为主要终点并作为批准新辅助治疗基础的优点和局限性。
