title: Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin.
abstract: OBJECTIVE
  Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting.
  
  
  METHODS
  Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year.
  
  
  RESULTS
  A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation.
  
  
  CONCLUSIONS
  Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.
authors.affiliation: Queen's University, Toronto, Ontario, Canada.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Morales
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Harry
authors.initials: H
authors.lastname: Herr
authors.affiliation: University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Gary
authors.initials: G
authors.lastname: Steinberg
authors.affiliation: Urology of Virginia, Virginia Beach, Virginia.
authors.forename: Robert
authors.initials: R
authors.lastname: Given
authors.affiliation: Bioniche Therapeutics Corp., Pointe-Claire, Quebec, Canada.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Cohen
authors.affiliation: Kingston and McDougall Scientific Ltd., Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Amrhein
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: akamat@mdanderson.org.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000283:Administration, Intravesical; D000368:Aged; D001500:BCG Vaccine / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009168:Mycobacterium phlei / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009696:Nucleic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D009696:Nucleic Acids
keywords: BCG vaccine; Mycobacterium phlei; nucleic acids; treatment failure; urinary bladder neoplasms