Authors

Neal D Shore, Carolina Urologic Research Center, Myrtle Beach, SC, United States
Stephen A Boorjian, Mayo Clinic, Rochester, MN, United States
Daniel J Canter, Ochsner Health System, New Orleans, LA, United States
Kenneth Ogan, Emory University, Atlanta, GA, United States
Lawrence I Karsh, Urology Center of Colorado, Denver, CO, United States
Tracy M Downs, University of Wisconsin, Madison, WI, United States
Leonard G Gomella, Thomas Jefferson University, Philadelphia, PA, United StatesFollow
Ashish M Kamat, University of Texas MD, Anderson Cancer Center, Department of Urology, Unit 1373, 1515 Holcombe Blvd, Houston, TX, United States
Yair Lotan, University of Texas Southwestern Medical Center, Dallas, United States
Robert S Svatek, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
Trinity J Bivalacqua, Johns Hopkins School of Medicine, Baltimore, MD, United States
Robert L Grubb, Washington University, St Louis, MO, United States
Tracey L Krupski, University of Virginia, Charlottesville, VA, United States
Seth P Lerner, Baylor College of Medicine, Houston, United States
Michael E Woods, University of North Carolina, Chapel Hill, United States
Brant A Inman, Duke University, Durham, NC, United States
Matthew I Milowsky, University of North Carolina, Chapel Hill, United States
Alan Boyd, Alan Boyd Consultants, Cottenham, United Kingdom
F Peter Treasure, Peter Treasure Statistical Services, King’s Lynn, United Kingdom
Gillian Gregory, FKD Therapies Oy, Gene Therapy Unit, Kuopio, Finland
David G Sawutz, FKD Therapies Oy, Gene Therapy Unit, Kuopio, Finland
Seppo Yla-Herttuala, A.I. Virtanen Institute University, Eastern Finland and Science Service Center, Gene Therapy Unit, Kuopio, Finland
Nigel R Parker, FKD Therapies Oy, Gene Therapy Unit, Kuopio, Finland
Colin P N Dinney, University of Texas MD, Anderson Cancer Center, Department of Urology, Unit 1373, 1515 Holcombe Blvd, Houston, TX, United States

Document Type

Article

Publication Date

10-20-2017

Comments

This article has been peer reviewed. It was published in: Journal of Clinical Oncology.

Volume 35, Issue 30, 20 October 2017, Pages 3410-3416.

The published version is available at DOI: 10.1200/JCO.2017.72.3064

Copyright © 2017 by American Society of Clinical Oncology

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 × 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.

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