Model-based Dose Individualization of Sunitinib in Gastrointestinal Stromal Tumors.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Maddalena CentanniL E Friberg

Abstract

Various biomarkers have been proposed for sunitinib therapy in gastrointestinal stromal tumor (GIST). However, the lack of "real-life" comparative studies hampers the selection of the most appropriate one. We, therefore, set up a pharmacometric simulation framework to compare each proposed biomarker. Models describing relations between sunitinib exposure, adverse events (hand-foot syndrome, fatigue, hypertension, and neutropenia), soluble VEGFR (sVEGFR)-3, and overall survival (OS) were connected to evaluate the differences in survival and adverse events under different dosing algorithms. Various fixed dosing regimens [4/2 (weeks on/weeks off) or 2/1 (50 mg), and continuous daily dosing (37.5 mg)] and individualization approaches [concentration-adjusted dosing (CAD), toxicity-adjusted dosing (TAD), and sVEGFR-3-adjusted dosing (VAD)] were explored following earlier suggested blood sampling schedules and dose-reduction criteria. Model-based forecasts of biomarker changes were evaluated for predictive accuracy and the advantage of a model-based dosing algorithm was evaluated for clinical implementation. The continuous daily dosing regimen was predicted to result in the longest survival. TAD (24.5 months) and VAD (25.5 months) inc...Continue Reading

References

Sep 1, 1979·Clinical Pharmacology and Therapeutics·L B SheinerV V Marathe
Jan 10, 2004·Clinical & Experimental Metastasis·Lesley J MurrayNancy K Pryer
Nov 30, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sandrine FaivreEric Raymond
May 17, 2007·Cancer Chemotherapy and Pharmacology·Carolyn D BrittenDennis Slamon
Mar 5, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brett E HoukMichael Amantea
Mar 14, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S GeorgeG D Demetri
Apr 9, 2010·Clinical Pharmacology and Therapeutics·A LindauerU Jaehde
Aug 4, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S GeorgeG D Demetri
Jul 10, 2013·CPT: Pharmacometrics & Systems Pharmacology·R J KeizerA Hooker
Oct 19, 2013·British Journal of Clinical Pharmacology·Brendan C BenderLena E Friberg
Dec 7, 2013·CPT: Pharmacometrics & Systems Pharmacology·E K HanssonM O Karlsson
Sep 24, 2014·Drug Discovery Today·Djoeke de WitNielka P van Erp
Nov 14, 2014·British Journal of Clinical Pharmacology·Huixin YuAlwin D R Huitema
Feb 24, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B I RiniV Grünwald
Sep 21, 2015·Redox Biology·L León-MateosL Antón Aparicio
Jul 2, 2017·Cancer Chemotherapy and Pharmacology·Dhanusha SabanathanHoward Gurney
Jul 13, 2017·Clinical Pharmacology and Therapeutics·Remy B VerheijenAlwin D R Huitema
Jul 4, 2019·British Journal of Clinical Pharmacology·Robin J SvenssonUlrika S H Simonsson
Nov 30, 2019·British Journal of Clinical Pharmacology·Kim WesterdijkUNKNOWN Dutch Pharmacology and Oncology Group (DPOG)
Dec 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S GeorgeG D Demetri
Apr 1, 2020·Frontiers in Pharmacology·Maddalena Centanni, Lena E Friberg
Apr 11, 2020·Clinical Pharmacology and Therapeutics·Rasmus Jansson-LöfmarkJohan Gabrielsson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Related Papers

Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners
Winnie ChengMário de Lemos
European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
S GeorgeGeorge D Demetri
© 2022 Meta ULC. All rights reserved