Phase 1b Trial to Evaluate Tissue Response to a Second Dose of Intravesical Recombinant Adenoviral Interferon α2b Formulated in Syn3 for Failures of Bacillus Calmette-Guerin (BCG) Therapy in Nonmuscle Invasive Bladder Cancer
| Autor: | William F. Benedict, Ashish M. Kamat, Guangcheng Zhang, Nancy Ainslie, Jay B. Shah, H. Barton Grossman, Colin P.N. Dinney, Neema Navai, Alice Abraham |
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| Rok vydání: | 2016 |
| Předmět: |
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medicine.medical_specialty Urinary system Genetic Vectors 030232 urology & nephrology Urology Alpha interferon Interferon alpha-2 Disaccharides Drug Administration Schedule Article Adenoviridae Efficacy Excipients 03 medical and health sciences 0302 clinical medicine medicine Humans Neoplasm Invasiveness Treatment Failure Adverse effect Aged Aged 80 and over Bladder cancer medicine.diagnostic_test Dose-Response Relationship Drug business.industry Interferon-alpha Cholic Acids Cystoscopy Genetic Therapy medicine.disease Recombinant Proteins Surgery Clinical trial Administration Intravesical Oncology Urinary Bladder Neoplasms 030220 oncology & carcinogenesis BCG Vaccine Neoplasm Recurrence Local business BCG vaccine |
| Zdroj: | Annals of surgical oncology. 23(12) |
| ISSN: | 1534-4681 |
| Popis: | A phase 1b trial was conducted to evaluate the duration of interferon-alpha (IFNα) production after intravesical administration of recombinant adenovirus-mediated interferon α2b (Ad-IFN) formulated with the excipient Syn3. The primary aim was to determine whether a second instillation 3 days after initial treatment produced prolonged urinary IFN production. The study enrolled seven patients who experienced recurrent non-muscle invasive bladder cancer after bacillus Calmette–Guerin therapy. Each treatment consisted of intravesical instillation of SCH721015 (Syn3) and Ad-IFN at a concentration of 3 × 1011 particles/mL to a total volume of 75 mL given on days 1 and 4. The patients were followed for 12 weeks, during which the magnitude and duration of gene transfer were determined by urine INFα levels. Drug efficacy was determined by cystoscopy and biopsy, and patients who had no recurrence at 12 weeks were eligible for a second course of treatment. Seven patients were treated with an initial course (instillation on days 1 and 4). Two of the patients had a complete response at 12 weeks and received a second course of treatment. One patient remained without evidence of recurrence after a second course (total 24 weeks). One patient experienced a non-treatment-associated adverse event. Despite a transient rise in IFNα levels, sustained production was not demonstrated. Previously, Ad-IFNα intravesical therapy has shown promising drug efficacy. A prior phase 1 trial with a single instillation compared similarly with the current study, suggesting that a second instillation is not necessary to achieve sufficient urinary IFNα levels. |
| Databáze: | OpenAIRE |
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