Anthracycline Analogs: The Past, Present, And Future

In the 1986 review, the authors examined the development of anthracycline analogs, particularly focusing on their role in cancer treatment and the quest to find alternatives with less cardiotoxicity than doxorubicin (DOX). Epirubicin (EPI) was highlighted for its similar antitumor efficacy to DOX but with reduced cardiotoxicity, as evidenced by animal studies and phase I clinical trials. The review also discussed the pharmacokinetics of EPI, noting its rapid metabolism and different elimination patterns compared to DOX. EPI was found to be effective in treating breast cancer and other malignancies where DOX is active, with phase II and III trials supporting its use. However, it was not effective against cancers resistant to DOX, such as colorectal and melanoma. The document also touched on other analogs like esorubicin (ESO) and MEN (7-con-O-methylnogarol), but their clinical potential was still uncertain at the time. The review concluded that while many analogs have been tested, only EPI showed a modest advantage over DOX, and the future of other analogs remained unclear. The authors called for improved screening methods and trial designs to better assess new compounds' cardiotoxicity and efficacy.