A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Li C, Agarwal P, Gibiansky E, Jin J, Dent S, Gonçalves A, Nijem I, Strasak A, Harle-Yge M, Chernyukhin N, LoRusso P, Girish S. A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function. Clinical Pharmacokinetics 2016, 56: 1069-1080. PMID: 27995530, DOI: 10.1007/s40262-016-0496-y.Peer-Reviewed Original ResearchConceptsNormal hepatic functionModerate hepatic impairmentHepatic impairmentMetastatic breast cancerHepatic functionTrastuzumab emtansineBreast cancerCycle 1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Phase I pharmacokinetic studyHuman epidermal growth factor receptorChild-Pugh criteriaMild hepatic impairmentT-DM1 3.6T-DM1 exposureGrowth factor receptor 2I pharmacokinetic studyFactor receptor 2Epidermal growth factor receptorGrowth factor receptorModerate cohortBaseline albuminT-DM1Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity
Schwartz GK, Dickson MA, LoRusso P, Sausville EA, Maekawa Y, Watanabe Y, Kashima N, Nakashima D, Akinaga S. Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity. Cancer Science 2016, 107: 499-506. PMID: 26850678, PMCID: PMC4832855, DOI: 10.1111/cas.12906.Peer-Reviewed Original ResearchConceptsOral tyrosine kinase inhibitorTyrosine kinase inhibitorsIGF-1RSolid tumorsHuman Phase I StudyInsulin-like growth factor receptor 1Colon carcinoma xenograft modelKinase inhibitorsHuman epidermal growth factor receptorPhase I clinical trialDose of KWModest antitumor activityAdvanced solid tumorsMetastatic breast cancerPhase I studiesGrowth factor receptor 1Human IGF-1RHuman malignant cell linesEpidermal growth factor receptorFactor receptor 1Inhibitory activityEvaluable patientsGrowth factor receptorMalignant cell linesStable disease