DeGeorge J J, Ahn C H, Andrews P A, Brower M E, Giorgio D W, Goheer M A, Lee-Ham D Y, McGuinn W D, Schmidt W, Sun C J, Tripathi S C
Division of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
Cancer Chemother Pharmacol. 1998;41(3):173-85. doi: 10.1007/s002800050726.
The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed.
新型抗癌治疗药物进入I期临床试验通常基于相对有限的临床前数据。本报告定义了在研究性新药申请（IND）下评估安全性所需的一系列重要临床前测试，并概述了从动物毒性研究推断I期临床试验中研究性抗癌药物起始剂量的依据。还讨论了支持新型抗癌药物上市的临床前研究类型。本报告阐述了细胞毒性药物（包括光敏剂和靶向递送产品）、长期使用的药物（化学预防药物、激素药物、免疫调节剂）以及旨在提高疗效（多药耐药逆转剂和放疗/化疗增敏剂）或降低当前使用的抗癌疗法毒性的药物在临床前开发中的异同。还讨论了在设计癌症治疗的联合疗法、替代疗法和辅助疗法的临床前研究以及支持临床制剂或给药途径变更时需要考虑的因素。
