Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts.
Ann Oncol
; 21(1): 98-103, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19889608
ABSTRACT
BACKGROUND:
Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. MATERIALS ANDMETHODS:
Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. RESULTS ANDCONCLUSION:
In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab')(2) fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras status.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França