title: Gemcitabine in patients with solid tumors and renal impairment: a pharmacokinetic phase I study.
abstract: The purpose of this phase I study was to determine the pharmacokinetics and toxicity of gemcitabine in patients with advanced, recurrent, and/or metastatic cancer and renal impairment. Patients were entered in 4 groups estimated by EDTA-Cr plasma clearance (CLp, mL/min): > or =80; > or =60 and <80; > or =30 and <60; and > or =30 and <80 plus renal insufficiency induced by previous chemotherapy, respectively. Gemcitabine 500 to 1000 mg/m was administered intravenously on days 1, 8, and 15 every 4 weeks. Plasma concentration data were pooled and analyzed using a population pharmacokinetic program (NONMEM). Eighteen white patients (14 females, 4 males) entered the study with a median age of 55 years. Linear regression analyses revealed no significant relationship between gemcitabine CLp and indices of renal impairment (EDTA-Cr CL; p = 0.797 or beta2-microglobulin; p = 0.153). Hematologic and nonhematologic toxicities were mild. Thus, there seems to be no significant impact of mild to moderate renal insufficiency on gemcitabine pharmacokinetics in patients with advanced cancer.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif, France. delaloge@igr.fr.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart
authors.forename: Mario
authors.initials: M
authors.lastname: Di Palma
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tourani
authors.forename: Francois
authors.initials: F
authors.lastname: Turpin
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: S T
authors.initials: ST
authors.lastname: Forgue
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Chevalier
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005467:Floxuridine / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; D000093542:Gemcitabine