Gemcitabine in leukemia: a phase I clinical, plasma, and cellular pharmacology study.
作者： R Grunewald , H Kantarjian , M Du , K Faucher , P Tarassoff
DOI: 10.1200/JCO.1992.10.3.406
关键词: Pharmacology 、 Distribution (pharmacology) 、 Chronic myelogenous leukemia 、 Leukemia 、 Immunology 、 Acute leukemia 、 Chemotherapy 、 Extracellular 、 Gemcitabine 、 Refractory 、 Medicine
摘要: PURPOSEPhase I clinical and in vitro studies of gemcitabine (2',2'-difluorodeoxycytidine; dFdC) have demonstrated that the accumulation rate dFdC 5'-triphosphate (dFdCTP) mononuclear leukemia cells is saturated when plasma or extracellular levels exceed 15 to 20 mumol/L. Thus, we designed a phase study maximize dFdCTP by administering at 10 mg/m2/min, dose calculated produce steady-state mumol/L.PATIENTS AND METHODSThe treatment intensity was increased patients (n = 22) with relapsed refractory acute chronic myelogenous (CML) blast crisis prolonging infusion duration but maintaining same rate. Doses between 1,200 mg/m2 6,400 were administered weekly for 3 weeks.RESULTSThe maximum-tolerated 4,800 infused over 480 minutes. The mean level all infusions 26.5 +/- 9 mumol/L 19). accum...
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