Journal article
Phase I Trial of Intravesical Recombinant Adenovirus Mediated Interferon-α2b Formulated in Syn3 for Bacillus Calmette-Guérin Failures in Nonmuscle Invasive Bladder Cancer
The Journal of urology, Vol.190(3), pp.850-856
09/2013
DOI: 10.1016/j.juro.2013.03.030
PMCID: PMC3951790
PMID: 23507396
Abstract
A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months.
A total of 17 patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment were enrolled in the study. A single treatment of rAd-IFNα (3 × 109 to 3 × 1011 particles per ml) formulated with the excipient Syn3 was administered. Patient safety was evaluated for 12 or more weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months.
Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity was encountered. Urgency was the most common adverse event and all cases 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 of 1010 or more particles per 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.
Intravesical rAd-IFNα/Syn3 was well tolerated with no dose limiting toxicity encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in nonmuscle invasive bladder cancer recurring after bacillus Calmette-Guérin.
Details
- Title: Subtitle
- Phase I Trial of Intravesical Recombinant Adenovirus Mediated Interferon-α2b Formulated in Syn3 for Bacillus Calmette-Guérin Failures in Nonmuscle Invasive Bladder Cancer
- Creators
- Colin P.N Dinney - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasMark B Fisher - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasNeema Navai - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasMichael A O'Donnell - Department of Urology, University of Iowa, Iowa City, IowaDavid Cutler - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaAlice Abraham - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasSophia Young - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaBeth Hutchins - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaMaria Caceres - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaNarendra Kishnani - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaGeorge Sode - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaConstance Cullen - Merck, Sharp and Dohme Corp., Upper Gwynedd, Pennsylvania, Union and Kenilworth, New Jersey, and Palo Alto, CaliforniaGuangcheng Zhang - Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TexasH. Barton Grossman - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasAshish M Kamat - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasMarshall Gonzales - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasMichael Kincaid - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasNancy Ainslie - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasDaniel C Maneval - Halozyme Therapeutics Inc., San Diego, CaliforniaMatthew F Wszolek - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TexasWilliam F Benedict - Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.190(3), pp.850-856
- DOI
- 10.1016/j.juro.2013.03.030
- PMID
- 23507396
- PMCID
- PMC3951790
- NLM abbreviation
- J Urol
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Publisher
- Elsevier Inc
- Grant note
- CA091846; CA016672 / Genitourinary Bladder Cancer SPORE and Cancer Center Core CS2005-00014622JS / Schering-Plough Research Institute T32CA079449 / National Research Service Award
- Language
- English
- Date published
- 09/2013
- Academic Unit
- Urology
- Record Identifier
- 9984051889002771
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