CLINICAL-APPLICATIONS OF THE CAMPTOTHECINS

The camptothecin topoisomerase I-targeting agents are new class of ant itumor drugs with demonstrated clinical activity in human malignancies , such as colorectal cancer and ovarian cancer. Currently, irinotecan and topotecan are the most widely used camptothecin analogs in clinica l use and clinical trials are ongoing to better characterize their spe ctra of clinical activity, to determine their optimal schedules of adm inistration and to define their use in combination with other chemothe rapeutic agents. Newer camptothecin analogs in clinical development, s uch as 9-aminocamptothecin, 9-nitrocamptothecin, GI147211 and DX-8951f , are also being studied to determine if they have improved toxicity a nd efficacy profiles compared with existing analogs. Other potential c linical applications include the use of camptothecin derivatives as ra diation sensitizers or as antiviral agents. The successful development of the camptothecins as antitumor agents highlights the importance of topoisomerase I as a target for cancer chemotherapy. 0167-4781/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved.