Tumor growth rate is an early indicator of antitumor drug activity in phase I clinical trials.
Tumor growth rate is an early indicator of antitumor drug activity in phase I clinical trials.
复制标题
DOI：
10.1158/1078-0432.ccr-13-2098
复制
发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Soria JC
中科院分区：
文献类型：
--
作者：
Ferté C;Fernandez M;Hollebecque A;Koscielny S;Levy A;Massard C;Balheda R;Bot B;Gomez-Roca C;Dromain C;Ammari S;Soria JC
RECIST评价未考虑治疗前肿瘤动力学，可能提供有关实验药物活性的不完整信息。肿瘤生长速率（TGR）允许对肿瘤动力学进行动态和定量评估。TGR如何随着实验性治疗的引入而沿着变化，以及与I期患者的结局相关仍是未知的。分析了20项I期试验中前瞻性治疗的所有患者（n=253）的病历。在给药前阶段（参考）和实验阶段计算TGR。计算TGR、标准预后评分（RMH评分）和结局（PFS、OS）之间的相关性（多变量分析）。我们观察到参考期与实验期之间的TGR降低（38%对4.4%，P<.00001）。尽管大多数患者在首次评估时被RECIST分类为疾病稳定（65%）或疾病进展（25%），但其中82%和65%的患者分别显示TGR降低。在多变量分析中，只有TGR的降低与PFS相关（P=.004），而RMH评分是唯一与OS相关的变量（P=.0008）。只有所研究的方案与TGR降低相关（P<0.00001，多变量分析）。在不同的临床试验中计算TGR谱揭示了抗肿瘤活性的特定模式。在I期患者中探索TGR很简单，并提供了临床相关信息：（i）早期和微妙的抗肿瘤活性体征评估;（ii）与PFS的独立相关性;（iii）它揭示了药物特异性特征;提示了指导研究药物进一步开发的潜在效用。
RECIST evaluation does not take into account the pre-treatment tumor kinetics and may provide incomplete information regarding experimental drug activity. Tumor Growth Rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. Medical records from all patients (n=253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pre-treatment period (REFERENCE) and the EXPERIMENTAL period. Associations between TGR, standard prognostic scores (RMH score) and outcome (PFS, OS) were computed (multivariate analysis). We observed a reduction of TGR between the REFERENCE vs. EXPERIMENTAL periods (38% vs. 4.4%, P<.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analyses, only the decrease of TGR was associated with PFS (P=.004), whereas the RMH score was the only variable associated with OS (P=.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P<.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity. Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) indpendent association with PFS; and (iii) It reveals drug-specific profiles; suggesting potential utility for guiding the further development of the investigational drugs.