Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib-Treated Patients With Gastrointestinal Stromal Tumors.

Autor: Schindler E; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden., Krishnan SM; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden., Mathijssen R; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Ruggiero A; Department of Radiology, Papworth Hospital NHS Foundation Trust, Cambridge University Health Partners, Cambridge, CB23 3RE, United Kingdom., Schiavon G; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Friberg LE; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2017 Jul; Vol. 6 (7), pp. 449-457. Date of Electronic Publication: 2017 May 30.
DOI: 10.1002/psp4.12195
Abstrakt: Three-dimensional and density-based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib-treated gastrointestinal patients, the time-courses of liver metastases' maximum transaxial diameters, software-calculated actual volumes (V actual ) and calculated ellipsoidal volumes were characterized by logistic growth models, in which imatinib induced a linear dose-dependent size reduction. An indirect response model best described the reduction in density. Substantial interindividual variability in the drug effect of all response assessments and additional interlesion variability in the drug effect on density were identified. The predictive ability of longitudinal tumor unidimensional and three-dimensional size and density on overall survival (OS) and progression-free survival (PFS) were compared using parametric time-to-event models. Death hazard increased with increasing V actual . This framework may guide early clinical interventions based on three-dimensional tumor responses to enhance benefits for patients with gastrointestinal stromal tumors (GIST).
(© 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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