Levin Victor A, Ictech Sandra, Hess Kenneth R
Department of Neuro-Oncology, Unit 431, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
BMC Cancer. 2007 Jun 22;7:106. doi: 10.1186/1471-2407-7-106.
To assess progression-free survival (PFS) as the appropriate end-point for phase II trials for anaplastic gliomas (AGs) and to determine the impact of PFS on survival-based phase III trials.
Combined data from 16 phase II studies (N = 529 patients) were analyzed to determine progression-free survival (PFS) at 6, 9, and 12 months and the impact of age, Karnofsky performance score (KPS), number of prior chemotherapies, and response to treatment on PFS.
The specific chemotherapy used was the major effector of PFS at 6, 9, and 12 months. Age, KPS, treatment response rate, and number of prior chemotherapies did not affect PFS to the same extent. Hierarchical cluster analyses and linear least squares fitting of PFS9 v PFS12 demonstrated the existence of three therapeutic efficacy groups with PFS rates at 6, 9, and 12 months ranging from lowest (A) to highest (C). The PFS6 was 15% in group A and 41% in group C (p < .0001); the PFS12 was 9% in group A and 33% in group C (p < .0001). Further, 80% of patients at recurrence had a 23% likelihood that each chemotherapy would provide > 1 year of additional life.
Based on PFS rates at 6, 9, and 12 months for AG patients, a differential of 1.5 to 2 years is the norm and could invalidate overall survival as an end-point for phase III studies in patients with AG. PFS is a more reliable end-point because it reflects the true antitumor benefit of the chemotherapy.
评估无进展生存期（PFS）作为间变性胶质瘤（AGs）II期试验的合适终点，并确定PFS对基于生存期的III期试验的影响。
分析来自16项II期研究（N = 529例患者）的合并数据，以确定6、9和12个月时的无进展生存期（PFS），以及年龄、卡诺夫斯基性能评分（KPS）、既往化疗次数和治疗反应对PFS的影响。
所使用的特定化疗是6、9和12个月时PFS的主要影响因素。年龄、KPS、治疗反应率和既往化疗次数对PFS的影响程度不同。PFS9与PFS12的层次聚类分析和线性最小二乘法拟合表明存在三个治疗疗效组，6、9和12个月时的PFS率从最低（A组）到最高（C组）。A组的PFS6为15%，C组为41%（p <.0001）；A组的PFS12为9%，C组为33%（p <.0001）。此外，复发时80%的患者每次化疗有23%的可能性提供超过1年的额外生命。
根据AG患者6、9和12个月时的PFS率，1.5至2年的差异是常态，这可能使总生存期作为AG患者III期研究的终点无效。PFS是一个更可靠的终点，因为它反映了化疗的真正抗肿瘤益处。
