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

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 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.
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https://www.hal.inserm.fr/inserm-00431431
Contributor : Yves Le Ster <>
Submitted on : Friday, November 12, 2010 - 7:00:07 AM
Last modification on : Monday, August 31, 2020 - 9:52:05 AM
Long-term archiving on: : Sunday, February 13, 2011 - 2:23:16 AM

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Christelle Larbouret, Bruno Robert, Caroline Bascoul-Mollevi, Frédérique Penault-Llorca, Alexandre Ho-Pun-Cheung, et al.. Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts.. Annals of Oncology, Elsevier, 2010, 21 (1), pp.98-103. ⟨10.1093/annonc/mdp496⟩. ⟨inserm-00431431⟩

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