III. Drugs that cause DNA strand breaks
Topoisomerase Inhibitors
(click here to review the difference between TopoI and TopoII)
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CCS: S and G2 phases
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ETOPOSIDE forms a complex with topoisomerase II and DNA that results in double-strand breaks - remains bound to the enzyme so that repair cannot occur
- IRINOTECAN and TOPOTECAN are potent inhibitors of topoisomerase I - causes single-strand breaks
- prodrugs (i.e., they must be activated)
- IRINOTECAN is eliminated by liver metabolism, and excreted in the bile and feces (see side effects)
- TOPOTECAN (and other "TECAN"s) are eliminated by a combination of metabolism and kidney excretion, making them better alternatives in some patients