2009
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors
LoRusso P, Markman B, Tabernero J, Shazer R, Nguyen L, Heath E, Patnaik A, Papadopoulos K. A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2009, 27: 3502-3502. DOI: 10.1200/jco.2009.27.15_suppl.3502.Peer-Reviewed Original ResearchAdverse eventsPhase I dose-escalation studyI dose-escalation studyDurable stable diseaseElevated hepatic transaminasesFood-induced increaseElevated liver enzymesNausea/vomitingSerious adverse eventsAdvanced solid tumorsDose-escalation studyPI3K pathway inhibitionClass I PI3K isoformsTumor growth inhibitionPI3K pathwayPharmacodynamic modulationQD regimenStable diseaseBID regimenHepatic transaminasesNeurological complaintsRepeat dosingPI3K isoformsPlasma insulinTolerable doses
2008
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 excretion