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Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts

Larbouret, C. ; Robert, B. ; Bascoul-Mollevi, C. ; Penault-Llorca, F. ; Ho-Pun-Cheung, A. ; Morisseau, S. ; Navarro-Teulon, I. ; Mach, J.-P ; Pèlegrin, A. ; Azria, D.

In: Annals of Oncology, 2009, vol. 21, no. 1, p. 98-103

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    Titre
    • Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts
    Auteur
    • Larbouret, C.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    • Robert, B.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    • Bascoul-Mollevi, C.. CRLC Val d'Aurelle Paul Lamarque, Montpellier
    • Penault-Llorca, F.. Department of Pathology Centre Jean Perrin, Clermont-Ferrand
    • Ho-Pun-Cheung, A.. CRLC Val d'Aurelle Paul Lamarque, Montpellier
    • Morisseau, S.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    • Navarro-Teulon, I.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    • Mach, J.-P. Institut de Biochimie, Université de Lausanne, Epalinges, Switzerland
    • Pèlegrin, A.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    • Azria, D.. Institut de Recherche en Cancérologie de Montpellier, Montpellier
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Annals of Oncology, 2009, vol. 21, no. 1, p. 98-103. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:302737
    Summary
    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 and methods: 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 and conclusion: 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