Neoadjuvant sorafenib, gemcitabine, and cisplatin administration preceding cystectomy in patients with muscle-invasive urothelial bladder carcinoma: An open-label, single-arm, single-center, phase 2 study.
Urol Oncol
; 36(1): 8.e1-8.e8, 2018 01.
Article
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| MEDLINE
| ID: mdl-28911922
ABSTRACT
BACKGROUND:
Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676). PATIENTS ANDMETHODS:
After transurethral resection of the bladder, T2-T4a N0 patients received four cycles of SGC followed by cystectomy. Sorafenib 400mg q12h daily, continuously, was added to standard GC chemotherapy. In a Simon's 2-stage design, the primary endpoint was the pathologic complete response (pT0), assuming H0 ≤0.20 and H1 ≥0.40, with a type I and type II error of 5% and 10%, respectively.RESULTS:
From April 2011 to June 2016, 46 patients were enrolled. Pathologic T0 response was obtained in 20 patients (43.5%, 95% CI 28.9-58.9); pT ≤ 1 in 25 (54.3%, 95% CI 39.0-69.1). After a median follow-up of 35 months, the median progression-free survival was not reached (NR, interquartile range 23.6-NR), nor was median overall survival (interquartile range 30.3-NR). Hematologic and extrahematologic grade 3 to 4 adverse events occurred in 45.6% and 26.1% of patients, respectively. In 29 samples from responders (pT ≤ 1) and nonresponders, different distribution of missense mutations involved DNA-repair genes, RAS-RAF pathway genes, chromatin-remodeling genes, and HER-family genes. ERCC1 immunohistochemical expression was associated with pT ≤ 1 response (P = 0.047). The absence of a comparator arm prevented us to quantify sorafenib contribution.CONCLUSIONS:
SGC combination was active in MIUBC, and the identified molecular features included alterations that may help personalize treatment in MIUBC with new more potent targeted agents, combined with chemotherapy.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
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Neoplasias de la Vejiga Urinaria
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Protocolos de Quimioterapia Combinada Antineoplásica
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Cistectomía
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Cisplatino
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Niacinamida
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Desoxicitidina
Idioma:
En
Revista:
Urol Oncol
Asunto de la revista:
NEOPLASIAS
/
UROLOGIA
Año:
2018
Tipo del documento:
Article