1. Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer
- Author
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B. Melichar, T. Csõszi, I. Lang, Jun Suk Kim, B. Belanger, Jung Sub Kim, J. B. Gallego, Joon Oh Park, A. Cubillo, Kun-Ming Rau, Wen Wee Ma, Mark Wong, B. S. Adiwijaya, J. Fitzgerald, Jen-Shi Chen, and I. Molnar
- Subjects
Adult ,Diarrhea ,Male ,medicine.medical_specialty ,Neutropenia ,Bilirubin ,Population ,Cmax ,Pharmacology ,Irinotecan ,030226 pharmacology & pharmacy ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Neoplasms ,medicine ,Humans ,Pharmacology (medical) ,education ,Aged ,Body surface area ,education.field_of_study ,Clinical Trials as Topic ,business.industry ,Research ,Articles ,Middle Aged ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,Liposomes ,Liposomal Irinotecan ,Camptothecin ,Female ,business ,medicine.drug - Abstract
Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.
- Published
- 2017