TY - JOUR
T1 - Intravesical rAd–IFNa/Syn3 for patients with high-grade, bacillus calmette-guerin–refractory or relapsed non–muscle-invasive bladder cancer
T2 - A phase II randomized study
AU - Shore, Neal D.
AU - Boorjian, Stephen A.
AU - Canter, Daniel J.
AU - Ogan, Kenneth
AU - Karsh, Lawrence I.
AU - Downs, Tracy M.
AU - Gomella, Leonard G.
AU - Kamat, Ashish M.
AU - Lotan, Yair
AU - Svatek, Robert S.
AU - Bivalacqua, Trinity J.
AU - Grubb, Robert L.
AU - Krupski, Tracey L.
AU - Lerner, Seth P.
AU - Woods, Michael E.
AU - Inman, Brant A.
AU - Milowsky, Matthew I.
AU - Boyd, Alan
AU - Treasure, F. Peter
AU - Gregory, Gillian
AU - Sawutz, David G.
AU - Yla-Herttuala, Seppo
AU - Parker, Nigel R.
AU - Dinney, Colin P.N.
N1 - Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
PY - 2017/10/20
Y1 - 2017/10/20
N2 - 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–IFNa/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–IFNa/ Syn3 (randomly assigned 1:1 to 1 3 1011 viral particles (vp)/mL or 3 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–IFNa/Syn3 (1 3 1011 vp/mL, n = 21; 3 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–IFNa/ 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—IFNa/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.
AB - 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–IFNa/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–IFNa/ Syn3 (randomly assigned 1:1 to 1 3 1011 viral particles (vp)/mL or 3 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–IFNa/Syn3 (1 3 1011 vp/mL, n = 21; 3 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–IFNa/ 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—IFNa/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.
UR - http://www.scopus.com/inward/record.url?scp=85030568757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030568757&partnerID=8YFLogxK
U2 - 10.1200/JCO.2017.72.3064
DO - 10.1200/JCO.2017.72.3064
M3 - Article
C2 - 28834453
AN - SCOPUS:85030568757
SN - 0732-183X
VL - 35
SP - 3410
EP - 3416
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -