%0 Journal Article %1 Houk.2009 %A Houk, B. E. %A Bello, C. L. %A Poland, B. %A Rosen, L. S. %A Demetri, G. D. %A Motzer, R. J. %D 2009 %J Cancer Chemother.Pharmacol. %K Blood Carcinoma Fatigue Pressure Research adverse blood effects methods response %T Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis %U PM:19967539 %X PURPOSE: In this pharmacokinetic/pharmacodynamic meta-analysis, we investigated relationships between clinical endpoints and sunitinib exposure in patients with advanced solid tumors, including patients with gastrointestinal stromal tumor (GIST) and metastatic renal cell carcinoma (mRCC). METHODS: Pharmacodynamic data were available for 639 patients of whom 443 had pharmacokinetic data. Sunitinib doses ranged from 25 to 150 mg QD or QOD. Models to express endpoint values and/or changes from baseline by the highest-correlating exposure measures were developed in S-PLUS or NONMEM using fixed- and mixed-effects modeling. RESULTS: Tentative relationships were identified between (1) steady-state AUC of total drug (sunitinib + its active metabolite SU12662) and time to tumor progression (TTP), overall survival (OS), with AUC significantly associated with longer TTP and OS in patients with GIST and mRCC, and incidence, but not severity, of fatigue; (2) steady-state AUC of sunitinib and respon

@article{Houk.2009, abstract = {PURPOSE: In this pharmacokinetic/pharmacodynamic meta-analysis, we investigated relationships between clinical endpoints and sunitinib exposure in patients with advanced solid tumors, including patients with gastrointestinal stromal tumor (GIST) and metastatic renal cell carcinoma (mRCC). METHODS: Pharmacodynamic data were available for 639 patients of whom 443 had pharmacokinetic data. Sunitinib doses ranged from 25 to 150 mg QD or QOD. Models to express endpoint values and/or changes from baseline by the highest-correlating exposure measures were developed in S-PLUS or NONMEM using fixed- and mixed-effects modeling. RESULTS: Tentative relationships were identified between (1) steady-state AUC of total drug (sunitinib + its active metabolite SU12662) and time to tumor progression (TTP), overall survival (OS), with AUC significantly associated with longer TTP and OS in patients with GIST and mRCC, and incidence, but not severity, of fatigue; (2) steady-state AUC of sunitinib and respon}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Houk, B. E. and Bello, C. L. and Poland, B. and Rosen, L. S. and Demetri, G. D. and Motzer, R. J.}, biburl = {https://www.bibsonomy.org/bibtex/2f3c3e1449b853fbb4c4fce87808fe341/kanefendt}, interhash = {5f95fc3888b2e146579684502e2fecbb}, intrahash = {f3c3e1449b853fbb4c4fce87808fe341}, journal = {Cancer Chemother.Pharmacol.}, keywords = {Blood Carcinoma Fatigue Pressure Research adverse blood effects methods response}, timestamp = {2010-02-05T11:28:51.000+0100}, title = {Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis}, url = {PM:19967539}, year = 2009 }