title: Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors.
abstract: OBJECTIVE
  To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors.
  
  
  METHODS
  Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1000, 1200 and 1500 mg/m(2) were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1500, 1800, and 2100 mg/m(2). Plasma concentrations of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine, were measured in 28 patients.
  
  
  RESULTS
  Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1200 mg/m(2). Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1500 mg/m(2) for 3 weeks, and one of seven patients at 1800 mg/m(2) for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2140 mL/min/m(2) and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months.
  
  
  CONCLUSIONS
  Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2100 mg/m(2) and 1200 mg/m(2), respectively.
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Reid
authors.forename: Wenchun
authors.initials: W
authors.lastname: Qu
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Safgren
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ames
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krailo
authors.forename: Nita L
authors.initials: NL
authors.lastname: Seibel
authors.forename: John
authors.initials: J
authors.lastname: Kuttesch
authors.forename: John
authors.initials: J
authors.lastname: Holcenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002675:Child, Preschool; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine