Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oncotarget ; 7(39): 64089-64099, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27577069

RESUMO

BACKGROUND: Prolonged anti-angiogenic therapy destroys tumor vasculature, whereas vascular-normalizing doses may enhance intra-tumoral drug delivery. We hypothesize that low-dose, short-course sunitinib normalizes vasculature, enhancing chemotherapy efficacy. PATIENTS AND METHODS: In phase Ib, treatment-naïve breast cancer patients received four cycles of pre-operative doxorubicin/cyclophosphamide, with sunitinib before each cycle. The optimal dose of sunitinib leading to tumor vessel normalization on immunohistochemistry was identified. In phase II, subjects were randomized to chemotherapy alone or chemotherapy plus sunitinib at the recommended phase II dose (RP2D). Primary endpoint was pathological complete response (pCR) rate. Tumor and functional imaging biomarkers were evaluated serially. RESULTS: In phase Ib (n=9), sunitinib 12.5 mg daily for 7 days before each chemotherapy was established as RP2D. In phase II, patients receiving chemotherapy plus sunitinib (n=24) had similar pCR rates (5.0% versus 4.3%, p=1.00), but a higher incidence of chemotherapy dose delays (33.3% versus 8.7%, p=0.04), compared to those receiving chemotherapy alone (n=25). The addition of sunitinib to chemotherapy significantly increased vascular normalization index (VNI) and decreased lymphatic vessel density (D2-40) on immunohistochemistry [VNI:25.50±27.94% versus 49.29±31.84%, p=0.034; D2-40:3.29±2.70 versus 1.29±1.54, p=0.014, baseline versus post-cycle 1], and improved perfusion on DCE-MRI (Ktrans:12.6±9.6 mL/100 g/min versus 16.3±10.7 mL/100 g/min, baseline versus post-cycle 1, p=0.015). Conversely, immunohistochemical and DCE-MRI parameters were not significantly altered by chemotherapy alone. CONCLUSION: Low-dose, short-course sunitinib prior to anthracycline-based chemotherapy in breast cancer patients did not improve pCR and increased chemotherapy dose delays. However, the addition of sunitinib induced compelling pharmacodynamic evidence of vascular normalization. Further studies with alternative cytotoxic regimens should be explored.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Indóis/administração & dosagem , Pirróis/administração & dosagem , Adulto , Idoso , Antraciclinas/administração & dosagem , Biomarcadores Tumorais , Meios de Contraste , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Período Pré-Operatório , Sunitinibe , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...