Intravesical rAd–IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin–Refractory or Relapsed Non–Muscle-Invasive Bladder Cancer: A Phase II Randomized Study Academic Article

abstract

  • Purpose Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd–IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd–IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.

authors

  • Shore, Neal D.
  • Boorjian, Stephen A.
  • Canter, Daniel J.
  • Ogan, Kenneth
  • Karsh, Lawrence, MD, FACS, CPI
  • Downs, Tracy M.
  • Gomella, Leonard G.
  • Kamat, Ashish M.
  • Lotan, Yair
  • Svatek, Robert S.
  • Bivalacqua, Trinity J.
  • Grubb, Robert L.
  • Krupski, Tracey L.
  • Lerner, Seth P.
  • Woods, Michael E.
  • Inman, Brant A.
  • Milowsky, Matthew I.
  • Boyd, Alan
  • Treasure, F. Peter
  • Gregory, Gillian
  • Sawutz, David G.
  • Yla-Herttuala, Seppo
  • Parker, Nigel R.
  • Dinney, Colin P.N.

Publication Date

  • 2017

webpage

published in

Digital Object Identifier (DOI)

number of pages

  • 6

start page

  • 3410

end page

  • 3416

volume

  • 35

issue

  • 30