title: Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.
abstract: OBJECTIVE
  The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder.
  
  
  METHODS
  Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg.
  
  
  RESULTS
  Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology).
  
  
  CONCLUSIONS
  Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.
authors.affiliation: Department of Urology, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. dalbagng@mskcc.org
authors.forename: Guido
authors.initials: G
authors.lastname: Dalbagni
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Joel
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: William
authors.initials: W
authors.lastname: Tong
authors.forename: Farhang
authors.initials: F
authors.lastname: Rabbani
authors.forename: Machelle S
authors.initials: MS
authors.lastname: Donat
authors.forename: Harry W
authors.initials: HW
authors.lastname: Herr
authors.forename: Pramod
authors.initials: P
authors.lastname: Sogani
authors.forename: Dominique
authors.initials: D
authors.lastname: dePalma
authors.forename: Dean
authors.initials: D
authors.lastname: Bajorin
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001500:BCG Vaccine / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001500:BCG Vaccine; D003841:Deoxycytidine; D000093542:Gemcitabine