title: Long-term clinical outcomes of a phase I trial of intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to standard intravesical therapy.
abstract: OBJECTIVE
  To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non-muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel.
  
  
  METHODS
  Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated.
  
  
  RESULTS
  With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months.
  
  
  CONCLUSIONS
  After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.
authors.affiliation: Department of Urology, Columbia University Medical Center, New York, New York, USA. Melissa.laudano@gmail.com
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Laudano
authors.forename: Lamont J
authors.initials: LJ
authors.lastname: Barlow
authors.forename: Alana M
authors.initials: AM
authors.lastname: Murphy
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
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage*; D013997:Time Factors; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel