Rebeccamycin is an antibiotic produced by the actinomycete, Saccharothrix aerocolonigenes, is a potent DNA intercalator and an inhibitor of the strand passing activity of topoisomerase II. However its mechanism of action is different from other topoisomerase inhibitors in that it does not stabilize the transiently formed tertiary intermediate complex. This is a phase I study of a rebeccamycin analogue that has shown anti- tumor activity against the P388 B16 melanoma, M5076 reticulum cell sarcoma, M109 lung cancer, HCT116 human colon carcinoma and A549 human lung cancer cell lines.
The specific aims of this study are: to determine the maximum tolerated dose of rebeccamycin; to determine the toxicities encountered; to determine the basic pharmacokinetics; to determine the relationship between the pharmacokinetics and toxicity data; to determine whenever possible the relationship between drug disposition and gender, race, or age; and to examine the mechanism of action of rebeccamycin by measurement of topoisomerase II inhibition.
Showing the most recent 10 out of 459 publications