Goffin John, Baral Stefan, Tu Dongsheng, Nomikos Dora, Seymour Lesley
National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Clin Cancer Res. 2005 Aug 15;11(16):5928-34. doi: 10.1158/1078-0432.CCR-05-0130.
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.
The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials 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.
Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. 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 II studies.
For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive.
早期试验中的肿瘤反应用于确定新药物是否值得进一步研究。鉴于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，特别是这两种肿瘤类型中的反应，是否能预测未来的监管药物批准。
回顾文献以评估在以下实体瘤的I期和II期试验中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之间的关系。
在100项I期试验中评估了58种药物，其中46种药物也在499项II期试验中进行了研究。I期试验（P = 0.03）和II期试验（P < 0.0001）中较高的总体反应率可预测监管批准。然而，黑色素瘤或肾细胞癌中的反应在I期或II期研究中均无预测性。
对于细胞毒性药物，虽然总体客观反应率能可靠地预测后续的上市批准，但黑色素瘤和肾细胞癌中的孤立反应并无预测性。
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