title: Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer.
abstract: OBJECTIVE
  In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies.
  
  
  METHODS
  Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high pressure liquid chromatography assay.
  
  
  RESULTS
  Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 microg/ml and the mean last AUC was 158 microg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels.
  
  
  CONCLUSIONS
  Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.
authors.affiliation: Department of Urology Fundació Puigvert, Universidad Autónoma de Barcelona, Spain. jpalou@fundacio-puigvert.es
authors.forename: Juan
authors.initials: J
authors.lastname: Palou
authors.forename: Antonio
authors.initials: A
authors.lastname: Carcas
authors.forename: Jose
authors.initials: J
authors.lastname: Segarra
authors.forename: Blanca
authors.initials: B
authors.lastname: Duque
authors.forename: Jose
authors.initials: J
authors.lastname: Salvador
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garcia-Ribas
authors.forename: Humberto
authors.initials: H
authors.lastname: Villavicencio
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000601:surgery; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine