OncoPharm Ifosfamide
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Nov 12, 2020 Explore the fascinating journey of ifosfamide, from its German origins to its role as a key oncology drug. Discover how this prodrug is activated and its implications for dosing and toxicity. Learn about its uses in treating lymphoma and sarcoma, along with specific FDA approvals for testicular cancer. Dive into discussions on emetogenicity, myelosuppression, and neurotoxicity risks, while also uncovering essential practices for preventing hemorrhagic cystitis with mesna. A detailed look at high-dose toxicities wraps up this insightful conversation.
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Origins With The Cyclophosphamide Team
- Ifosfamide was developed by the same German company that made cyclophosphamide as part of a search for tumor-activated prodrugs.
- Its discovery traces to 1930s research targeting phosphoramidase in solid tumors and human trials in the 1970s.
Prodrug Activation Shapes Ifosfamide's Profile
- Ifosfamide is a prodrug activated by hepatic CYP enzymes into an alkylating phosphoramide mustard.
- Its activation and metabolism create distinct toxic metabolites that shape its clinical profile.
Slower Activation Explains Dose And Toxicity
- Ifosfamide activates about fourfold slower than cyclophosphamide, necessitating higher doses.
- Slower activation increases generation of toxic metabolites like acrolein and 2-chloroacetyl aldehyde.