title: Phase II trial of intravesical nanoparticle albumin bound paclitaxel for the treatment of nonmuscle invasive urothelial carcinoma of the bladder after bacillus Calmette-Guérin treatment failure.
abstract: OBJECTIVE
  Response rates to current second line intravesical therapies for recurrent nonmuscle invasive bladder cancer range between 10% and 30%. Nanoparticle albumin bound (nab-)paclitaxel has increased solubility and lower toxicity compared to other taxanes. Results of the phase I intravesical trial of this compound demonstrated minimal toxicity during dose escalation. We now report the results of a phase II trial to assess efficacy.
  
  
  METHODS
  This study was an investigator initiated, single center, single arm, phase II trial investigating the use of nab-paclitaxel in patients with recurrent Tis, T1 and Ta urothelial carcinoma in whom at least 1 prior regimen of intravesical bacillus Calmette-Guérin failed. Patients received 500 mg/100 ml nab-paclitaxel administered in 6 weekly intravesical instillations. Efficacy was evaluated with cystoscopy, biopsy, cytology and imaging. If complete response was achieved, patients were treated with full dose monthly maintenance treatments for 6 months.
  
  
  RESULTS
  A total of 28 patients were enrolled in the study. Of these patients 10 (35.7%) exhibited a complete response after initial treatment. At 1 year all of these responses remained durable after maintenance therapy. At a mean followup of 21 months (range 5 to 47) 19 of 28 (67.8%) patients retained their bladders without progression or distant metastases. A single patient had progression to muscle invasive disease at radical cystectomy. Treatment related adverse events were noted in 9 of 28 (32.1%) patients and were limited to grade 1 or 2.
  
  
  CONCLUSIONS
  Intravesical nab-paclitaxel has minimal toxicity and a 35.7% response rate in patients with nonmuscle invasive bladder cancer and previous bacillus Calmette-Guérin failure. Complete response remained durable at 1 year followup in this heavily pretreated patient population.
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York. Electronic address: jmm23@columbia.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Dara D
authors.initials: DD
authors.lastname: Holder
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Rashed A
authors.initials: RA
authors.lastname: Ghandour
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: LaMont J
authors.initials: LJ
authors.lastname: Barlow
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ahn
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Max
authors.initials: M
authors.lastname: Kates
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Badalato
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York, New York.
authors.forename: Arindam
authors.initials: A
authors.lastname: Roychoudhury
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: G Joel
authors.initials: GJ
authors.lastname: Decastro
authors.affiliation: Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000627:therapeutic use*; D011446:Prospective Studies; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000276:Adjuvants, Immunologic; D000418:Albumins; D001500:BCG Vaccine; D017239:Paclitaxel
keywords: intravesical administration; investigational; nanotechnology; paclitaxel; therapies; urinary bladder neoplasms