Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Ramanathan R, Egorin M, Takimoto C, Remick S, Doroshow J, LoRusso P, Mulkerin D, Grem J, Hamilton A, Murgo A, Potter D, Belani C, Hayes M, Peng B, Ivy S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 563-569. PMID: 18235115, DOI: 10.1200/jco.2007.11.0304.Peer-Reviewed Original ResearchConceptsNausea/vomitingLiver dysfunctionLiver functionLD groupNational Cancer Institute Organ Dysfunction Working GroupLiver function test elevationsPlasma concentration-time curveD dose levelDose of imatinibDoses of imatinibSevere liver dysfunctionDose-limiting toxicityMild liver dysfunctionSerum total bilirubinNormal liver functionPharmacokinetics of imatinibDose-normalized areaConcentration-time curveConcentrations of imatinibImatinib doseAdvanced malignanciesImatinib exposureMaximal doseImatinib mesylateRenal excretionPhase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Gibbons J, Egorin M, Ramanathan R, Fu P, Mulkerin D, Shibata S, Takimoto C, Mani S, LoRusso P, Grem J, Pavlick A, Lenz H, Flick S, Reynolds S, Lagattuta T, Parise R, Wang Y, Murgo A, Ivy S, Remick S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 570-576. PMID: 18235116, DOI: 10.1200/jco.2007.13.3819.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseSerious adverse eventsDose-limiting toxicityImatinib dosesGroup patientsRenal dysfunctionImatinib exposureNormal groupNational Cancer Institute Organ Dysfunction Working GroupAlpha-1-acid glycoprotein concentrationSerum alpha-1-acid glycoprotein concentrationsMild group patientsRenal dysfunction groupModerate renal dysfunctionAdvanced solid tumorsPharmacokinetics of imatinibAcid glycoprotein concentrationPlasma AGP concentrationImatinib clearanceImatinib dosePlasma imatinibStable diseaseDysfunction groupRenal impairmentAdult patients