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| [PMID]: | 28834453 |
| [Au] Autor: | Shore ND; Boorjian SA; Canter DJ; Ogan K; Karsh LI; Downs TM; Gomella LG; Kamat AM; Lotan Y; Svatek RS; Bivalacqua TJ; Grubb RL; Krupski TL; Lerner SP; Woods ME; Inman BA; Milowsky MI; Boyd A; Treasure FP; Gregory G; Sawutz DG; Yla-Herttuala S; Parker NR; Dinney CPN |
| [Ad] Endereço: | Neal D. Shore, Carolina Urologic Research Center, Myrtle Beach, SC; Stephen A. Boorjian, Mayo Clinic, Rochester, MN; Daniel J. Canter, Ochsner Health System, New Orleans, LA; Kenneth Ogan, Emory University, Atlanta, GA; Lawrence I. Karsh, The Urology Center of Colorado, Denver, CO; Tracy M. Downs, U |
| [Ti] Título: | Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. |
| [So] Source: | J Clin Oncol;35(30):3410-3416, 2017 Oct 20. | | [Is] ISSN: | 1527-7755 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | 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 viral particles (vp)/mL or 3 × 10 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 vp/mL, n = 21; 3 × 10 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. |
| [Mh] Termos MeSH primário: |
Terapia Genética/métodos
Interferon-alfa/metabolismo
Neoplasias da Bexiga Urinária/terapia
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| [Mh] Termos MeSH secundário: |
Adenoviridae/genética
Administração Intravesical
Idoso
Idoso de 80 Anos ou mais
Vacina BCG/administração & dosagem
Ácidos Cólicos/química
Dissacarídeos/química
Resistência a Medicamentos Antineoplásicos
Fadiga/etiologia
Feminino
Terapia Genética/efeitos adversos
Vetores Genéticos/administração & dosagem
Vetores Genéticos/genética
Seres Humanos
Interferon-alfa/química
Interferon-alfa/genética
Masculino
Meia-Idade
Gradação de Tumores
Invasividade Neoplásica
Recidiva Local de Neoplasia
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Resultado do Tratamento
Neoplasias da Bexiga Urinária/genética
Neoplasias da Bexiga Urinária/patologia
Transtornos Urinários/etiologia
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| [Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL |
[Nm] Nome de substância:
| 0 (BCG Vaccine); 0 (Cholic Acids); 0 (Disaccharides); 0 (Interferon-alpha); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Syn3 compound); 43K1W2T1M6 (interferon alfa-2b) |
| [Em] Mês de entrada: | 1710 |
| [Cu] Atualização por classe: | 171103 |
[Lr] Data última revisão:
| 171103 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170824 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1200/JCO.2017.72.3064 |
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