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 ( 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.


Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.