Irinotecan is a potent inhibitor of topoisomerase I, a critical enzyme in the DNA replication and transcription process. However, the clinical application of this chemotherapeutic agent is restricted by rapid elimination from the body and major dose-limiting toxicities.
Onivyde® is formulated as a nanoliposomal dispersion of irinotecan to provide improved stability. Following administration of a 70mg/m2 dose of Onivyde®, the terminal half-life of total irinotecan is 26.8 hours and 49.3 hours for the active metabolite, SN-38. In comparison, non-liposomal irinotecan has a mean terminal half-life of around six to twelve hours and ten to twenty hours for SN-38. Nanoliposomal encapsulation is also associated with improved tumour biodistribution and less accumulation in organs responsible for dose-limiting toxicities.
Onivyde® is indicated for the treatment of metastatic adenocarcinoma of the pancreas in combination with 5-fluorouracil and folinic acid in adults previously treated with gemcitabine-based therapy. The NAPOLI-1 trial investigated the use of 5-fluoruracil plus folinic acid in a control group with the study group also receiving nanoliposomal irinotecan. The primary endpoint, overall survival, was 45% higher in the study group compared to the control group.
The most frequently reported adverse reactions leading to discontinuation during clinical trials were vomiting and diarrhoea. Diarrhoea can be severe and life-threatening and may present as either early onset, late onset, or both. Febrile neutropenia and interstitial lung disease are other possible adverse reactions. Premedication with dexamethasone and a 5-HT3 antagonist is recommended at least half an hour before the Onivyde® infusion commences.
- Onivyde® (nanoliposomal irinotecan) Australian approved product information. Old Toongabbie: Baxalta. Approved December 2016.
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