CLINICAL TRIALS AND OBSERVATIONS Ancestry and pharmacogenetics of antileukemic drug toxicity
نویسندگان
چکیده
1Department of Pharmaceutical Sciences, St Jude Children’s Research Hospital, Memphis, TN; 2Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN; 3Hematologic Malignancies Program, St Jude Children’s Research Hospital, Memphis, TN; 4Department of Psychiatry, Pediatrics, and Human Genetics, University of Chicago, IL; 5Oncology, St Jude Children’s Research Hospital, Memphis, TN; 6University of Tennessee, Memphis; 7Clinica Pediatrica, Università di Milano, Milan, Monza, Italy; 8Biostatistics, M. D. Anderson Cancer Center, Houston, TX; 9DNAPrint Genomics, Sarasota, FL
منابع مشابه
Key observations from the NHLBI Asthma Clinical Research Network.
The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate it...
متن کاملCLINICAL TRIALS AND OBSERVATIONS Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics
Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patie...
متن کاملDose‐finding methods for Phase I clinical trials using pharmacokinetics in small populations
The aim of phase I clinical trials is to obtain reliable information on safety, tolerability, pharmacokinetics (PK), and mechanism of action of drugs with the objective of determining the maximum tolerated dose (MTD). In most phase I studies, dose-finding and PK analysis are done separately and no attempt is made to combine them during dose allocation. In cases such as rare diseases, paediatric...
متن کاملCLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial
R115777 is a nonpeptidomimetic enzymespecific inhibitor of farnesyl protein transferase (FT) that was developed as a potential inhibitor of Ras protein signaling, with antitumor activity in preclinical models. This study was a phase 1 trial of orally administered R115777 in 35 adults with poor-risk acute leukemias. Cohorts of patients received R115777 at doses ranging from 100 mg twice daily (b...
متن کاملCLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo
Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy with these agents. Patients were rando...
متن کامل