Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-EGF receptor 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 were observed.
Results and Conclusion
In first-line therapy, mice survival was significantly longer in 2mAbs groups compared to gemcitabine (p<0.0001: BxPC-3; p=0.0679: MiaPaCa-2; p=0.0019: Capan-1) and to 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, BxPC-3; p=0.05; MiaPaCa-2; p<0.001, 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 to controls (p=0.001), indicating that the 2mAbs had an, Fc-independent, direct action on tumor cells.
This pre-clinical study demonstrated a significant improvement of survival and tumour regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first and second-line treatments, compared to gemcitabine, independently of the K-Ras status.