title: Pharmacokinetics and toxicity of an early single intravesical instillation of gemcitabine after endoscopic resection of superficial bladder cancer.
abstract: BACKGROUND
  The tolerability and plasma absorption of gemcitabine administered at 40 mg/ml after small and extensive endoscopic transurethral resection of bladder tumors (TURB) were evaluated.
  
  
  METHODS
  Nine patients with a history of recurrent superficial bladder cancer were eligible for a single immediate, post TURB, intravesical instillation of gemcitabine. The endoscopic resection was small in 5 patients and extensive in 4. The drug was administered at 40 mg/ml concentration (2000 mg in 50 ml saline) and held in the bladder for 1 hour. Plasma concentrations of gemcitabine and its metabolite (2',2'-difluorodeoxyuridine) were determined with a validated HPLC assay. The blood count and chemistry were performed one day and one week postoperatively.
  
  
  RESULTS
  Toxicity was comparable for patients who underwent small or large TURB. The most significant side-effects were grade 2 vomiting and a transient grade 2 leukopenia after small and large TURB respectively. Mean maximum gemcitabine concentrations were 1.47 microg/ml in small TURB and 2.8 microg/ml in large TURB. The highest peak concentration of 4.26 microg/ml was found after extended bladder resection.
  
  
  CONCLUSIONS
  A single, immediate postoperative, intravesical instillation of gemcitabine at high concentration is feasible with acceptable toxicity, and it may be considered as an option taking into account patient performance status, tumor characteristics and TURB extension.
authors.affiliation: Division of Urology, E.O. Ospedali Galliera, Genoa, Italy. fabio.campodonico@galliera.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Campodonico
authors.forename: Francesca
authors.initials: F
authors.lastname: Mattioli
authors.forename: Valeria
authors.initials: V
authors.lastname: Manfredi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Capponi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pasquini
authors.forename: Antonietta
authors.initials: A
authors.lastname: Martelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffezzini
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine