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.

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 × 10(11) viral particles (vp)/mL or 3 × 10(11) 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 × 10(11) vp/mL, n = 21; 3 × 10(11) 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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Aug 23 [Epub ahead of print]

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

Neal D. Shore, Carolina Urologic Research Center, Myrtle Beach, SC; Stephen A. Boorjian, Mayo Clinic, Rochester, MN; Daniel J. Canter, Ochsner Health System, New Orleans, LA; Kenneth Ogan, Emory University, Atlanta, GA; Lawrence I. Karsh, The Urology Center of Colorado, Denver, CO; Tracy M. Downs, University of Wisconsin, Madison, WI; Leonard G. Gomella, Thomas Jefferson University, Philadelphia, PA; Ashish M. Kamat and Colin P.N. Dinney, University of Texas MD Anderson Cancer Center; Seth P. Lerner, Baylor College of Medicine, Houston; Yair Lotan, University of Texas Southwestern Medical Center, Dallas; Robert S. Svatek, University of Texas Health Science Center at San Antonio, San Antonio, TX; Trinity J. Bivalacqua, Johns Hopkins School of Medicine, Baltimore, MD; Robert L. Grubb III, Washington University, St Louis, MO; Tracey L. Krupski, University of Virginia, Charlottesville, VA; Michael E. Woods and Matthew I. Milowsky, University of North Carolina, Chapel Hill; Brant A. Inman, Duke University, Durham, NC; Alan Boyd, Alan Boyd Consultants, Cottenham; F. Peter Treasure, Peter Treasure Statistical Services, King's Lynn, United Kingdom; Gillian Gregory, David G. Sawutz, and Nigel R. Parker, FKD Therapies Oy; and Seppo Yla-Herttuala, A.I. Virtanen Institute University of Eastern Finland and Science Service Center and Gene Therapy Unit, Kuopio, Finland.

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