title: Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy.
abstract: OBJECTIVE
  Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent.
  
  
  METHODS
  This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging.
  
  
  RESULTS
  Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression.
  
  
  CONCLUSIONS
  Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.
authors.affiliation: Columbia University Medical Center, 161 Fort Washington Ave, 11th Floor, Department of Urology, New York, NY 10032, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
authors.forename: Puneet
authors.initials: P
authors.lastname: Masson
authors.forename: Alana M
authors.initials: AM
authors.lastname: Murphy
authors.forename: Manlio
authors.initials: M
authors.lastname: Goetzl
authors.forename: Carl A
authors.initials: CA
authors.lastname: Olsson
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel