Betsch B
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
J Cancer Res Clin Oncol. 1990;116(5):467-9. doi: 10.1007/BF01612995.
Sexual-steroid-hormone-linked anticancer agents are a new group of cytotoxic drugs designed for a site-directed chemotherapy of tumors containing sexual steroid hormone receptors. The hormone (e.g. estradiol or testosterone) should act as a carrier that leads to a preferential receptor-mediated drug accumulation in hormone-receptor-positive tumors (such as mammary carcinomas and prostatic cancer). In several preclinical therapeutic studies of sexual-hormone-receptor-positive breast cancer, for instance, conjugates of 2-chloroethyl-carbamoyl-L-alanine linked to estradiol or dihydrotestosterone showed, in comparison to the unlinked single agent, a significantly higher antineoplastic activity and a clearly lower systemic toxicity. But there is still only limited knowledge about the pharmacokinetic properties and the mode of action of these new drugs. For this reason in the present article a more comprehensive pharmacokinetic model and the pattern of distribution of new sexual-steroid-hormone-linked anticancer agents have been described.
性甾体激素连接的抗癌药是一类新型细胞毒性药物，专为含有性甾体激素受体的肿瘤进行靶向化疗而设计。激素（如雌二醇或睾酮）应作为载体，使药物在激素受体阳性肿瘤（如乳腺癌和前列腺癌）中通过受体介导实现优先蓄积。例如，在几项针对性激素受体阳性乳腺癌的临床前治疗研究中，与未连接的单一药物相比，连接了雌二醇或二氢睾酮的2-氯乙基-氨基甲酰-L-丙氨酸缀合物显示出显著更高的抗肿瘤活性和明显更低的全身毒性。但对于这些新药的药代动力学特性和作用方式仍知之甚少。因此，在本文中描述了一种更全面的药代动力学模型以及新型性甾体激素连接的抗癌药的分布模式。
