Your browser doesn't support javascript.
loading
A phase II study of the combination of endocrine treatment and bortezomib in patients with endocrine-resistant metastatic breast cancer.
Trinh, X B; Sas, L; Van Laere, S J; Prové, A; Deleu, I; Rasschaert, M; Van de Velde, H; Vinken, P; Vermeulen, P B; Van Dam, P A; Wojtasik, A; De Mesmaeker, P; Tjalma, W A; Dirix, L Y.
Afiliação
  • Trinh XB; Oncology Centre/Translational Cancer Research Unit Antwerp, St. Augustinus Hospital, GZA hospitals, Oosterveldlaan 24, 2610 Antwerp, Belgium.
Oncol Rep ; 27(3): 657-63, 2012 Mar.
Article em En | MEDLINE | ID: mdl-22134540
ABSTRACT
The majority of patients with hormone receptor-positive metastatic breast cancer die from disease progression despite different types of anti-hormonal treatments. Preclinical studies have indicated that resistance to anti-hormonal therapies may be the result of an activated NF-κB signalling pathway in breast cancer. Bortezomib is a proteasome inhibitor that blocks the NF-κB pathway. Recent pharmacodynamic and pharmaco-kinetic xenograft studies have shown that drug exposure may be a crucial factor for the efficacy of bortezomib in solid tumours. The aim was to investigate whether the addition of bortezomib to anti-hormonal therapy would result in regained antitumour activity in patients with progressive and measurable disease being treated with an endocrine agent. Clinical benefit was defined as patients obtaining stable disease, partial response or complete response after 2 cycles, lasting for at least another five weeks. Bortezomib was administered on days 1, 8, 15 and 22 of a 5-week regimen (1.6 mg/m2). Eight patients received an aromatase inhibitor and bortezomib, while one received tamoxifen and bortezomib. There were 3 grade 3 gastrointestinal toxicities. Median time to treatment failure was 69 days (range, 35-140). Two out of the 9 patients had stable disease for more than 10 weeks. Despite an effective target inhibition, suggested in peripheral blood mononuclear cells and available tumour samples, no objective antitumour responses were observed. Addition of a proteasome inhibitor to anti-hormonal therapy resulted in a clinical benefit rate of 22% in a limited number of patients with endocrine resistant and progressive metastatic breast cancer. The demonstrated proteasome inhibition in tumour tissue provides evidence that the lack of clinical responses is not attributed to deficient drug exposure.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Limite: Aged / Female / Humans / Middle aged Idioma: En Revista: Oncol Rep Assunto da revista: NEOPLASIAS Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Bélgica

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Protocolos de Quimioterapia Combinada Antineoplásica Limite: Aged / Female / Humans / Middle aged Idioma: En Revista: Oncol Rep Assunto da revista: NEOPLASIAS Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Bélgica
...