Class:
- Topoisomerase I inhibitor (camptothecin derivative)
Mechanism of Action:
- Inhibits the enzyme topoisomerase I, which relaxes DNA supercoiling during replication and transcription.
- Causes stabilization of the topoisomerase I-DNA cleavable complex, leading to DNA strand breaks, replication arrest, and apoptosis of cancer cells.
Clinical Use:
- Exatecan itself is not widely used as a standalone chemotherapeutic agent.
- Its derivative deruxtecan (a more potent form) is commonly used as the cytotoxic payload in antibody-drug conjugates (ADCs) such as fam-trastuzumab deruxtecan (Enhertu).
Pharmacist Considerations:
- Understanding exatecan’s mechanism aids in comprehending the activity and toxicities of ADCs containing its derivatives.
- Toxicities associated with topoisomerase I inhibitors include myelosuppression, gastrointestinal symptoms, and risk of interstitial lung disease when used in ADC form.