OncoPharm Irinotecan
41 snips
Aug 29, 2019 Dive into the fascinating world of irinotecan, a chemotherapy drug rooted in the ancient use of camptothecin. Explore how genetic differences impact treatment outcomes and side effects. Learn about the drug's complex dosing considerations and the notorious issue of diarrhea. Discover recent innovations, like the FDA-approved liposomal formulation, and how pharmacogenetic insights are reshaping personalized cancer care.
AI Snips
Chapters
Transcript
Episode notes
Irinotecan's Mechanism and Origin
- Irinotecan is a topoisomerase 1 inhibitor that traps DNA breaks leading to cell death.
- It is derived from camptothecin found in the Campotheca acuminata tree, historically used in herbal medicines.
UGT1A1 Polymorphisms Affect Metabolism
- Interpatient variability in irinotecan metabolism largely arises from differences in converting SN38 to its inactive form.
- The enzyme UGT1A1 glucuronidates SN38; genetic polymorphisms affect metabolism and toxicity risk.
Genotype-Guided Dosing Insight
- Maximum tolerated irinotecan doses depend on UGT1A1 genotype, with star 28 homozygous patients needing significant reductions.
- Standard dosing can lead to toxicity in deficient metabolizers and underdosing in wild types.