PURPOSE: A Phase l trial of intravesical recombinant adenovirus-mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with non-muscle invasive bladder cancer (NMIBC) who recurred after Bacillus Calmette-Guerin (BCG).
The primary objective was to determine the safety of rAd-IFNα/Syn3; secondary endpoints were to demonstrate effective rAd-IFNα gene expression and preliminary evidence of clinical activity at three months.
PATIENTS AND METHODS: Seventeen patients with recurrent NMIBC after BCG were enrolled. A single treatment of rAd-IFNα (3x109 to 3x1011 particles/mL) formulated with the excipient Syn3 was administered. Patient safety was evaluated for ≥12 weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months.
RESULTS: Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity (DLT) was encountered. Urgency was the most common adverse event and all were grade 1 or 2. rAd-IFNα DNA was not detected in the blood, however, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose-related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses ≥ 1010 particles/mL with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease free at 29.0 and 39.2 months respectively.
CONCLUSION: Intravesical rAd-IFNα/Syn3 was well tolerated with no DLT encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in NMIBC recurring after BCG.
Dinney CP, Fisher MB, Navai N, O'Donnell MA, Cutler D, Abraham A, Young S, Hutchins B, Caceres M, Kishnani N, Soder G, Cullen C, Zhang G, Grossman HB, Kamat AM, Gonzales M, Kincaid M, Ainslie N, Maneval DC, Wszolek MF, Benedict WF. Are you the author?
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Reference: J Urol. 2013 Mar 15. pii: S0022-5347(13)03676-8.