Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval
Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval
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DOI：
10.1158/1078-0432.ccr-05-0130
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发表时间：
2005-08-15
影响因子：
11.5
通讯作者：
Seymour, L
中科院分区：
文献类型：
--
作者：
Goffin, J;Baral, S;Seymour, L
目的：早期试验中的肿瘤反应用于确定新药是否值得进一步研究。鉴于在黑色素瘤和肾细胞癌中观察到自发消退，本研究评估了肿瘤反应（尤其是这两种肿瘤类型）是否可以预测未来监管药物的批准。 实验设计：回顾文献以评估以下实体瘤中 I 期和 II 期细胞毒性药物的肿瘤反应率：黑色素瘤、肾细胞癌、非小细胞肺癌、乳腺癌、卵巢癌、结直肠癌和其他实体瘤。对反应率进行分类，并确定这些类别与监管药物批准终点的关系。结果：在 100 项 I 期试验中评估了 58 种药物，在 499 项 II 期试验中还研究了其中的 46 种药物。 I 期试验 (P = 0.03) 和 II 期试验 (P < 0.0001) 中较高的总体缓解率预示着监管部门的批准。然而，黑色素瘤或肾细胞癌的反应不能预测 I 期或 II 期研究。结论：对于细胞毒性药物，虽然总体客观反应率可靠地预测随后的上市批准，但黑色素瘤和肾细胞癌的单独反应不能预测。
Purpose: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval.Experimental Design: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and IIrials in the following solid tumors: melanoma, renal cell carcinoma, non small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined.Results: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase IIrials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase IItudies.Conclusions: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive.