Comparison of combination anti-EGFR and anti-VEGFR2 therapy to MTD standard chemotherapeutic regimens

4097 The initial aim of targeted therapy was to achieve anticancer effects comparable to cytotoxic therapies, with more limited toxicity to normal tissue. Combining targeted therapies currently offers the best chance of achieving this goal. Here we have compared the efficacy of a combination of IgG1 monoclonal antibodies targeting EGFR (cetuximab) and VEGFR2 (DC101) to a maximum tolerated dose (MTD) of standard chemotherapeutic combination used in the clinic. Cetuximab+DC101 was compared to Irinotecan/5-FU/Leucovorin (IFL) and 5-FU/Leucovorin/oxaliplatin (FOLFOX) in 5 subcutaneous xenograft models of colon cancer. The combination targeted therapy approach had greater efficacy than FOLFOX and IFL in the DLD-1 and HCT-8 models, and very similar efficacy in the GEO and HCT-116 model. In the KM-12 model, cetuximab+DC101 matched the efficacy of FOLFOX but was less efficacious than IFL. In an orthotopic model where luciferase expressing HT-29 cells were injected into the rectal lining, cetuximab+DC101 matched the ability of FOLFOX and IFL to inhibit primary tumor growth and lymph node metastasis. Cetuximab+DC101 was also compared to MTD gemcitabine in 3 subcutaneous xenograft models of pancreatic cancer. The combination targeted therapy approach achieved significantly greater efficacy than gemcitabine in the BxPC-3 model, and similar efficacy in the HPAC and Mia Paca-2 models. In an orthotopic model in which luciferase expressing L3.7Pl cells were injected into the tail of the pancreas, cetuximab+DC101 achieved greater inhibition than gemcitabine in terms of primary tumor growth inhibition and a trend for reduction in liver metastasis. Thus combination targeted therapy with VEGFR2 and EGFR monoclonal antibodies has the potential to reduce the use of more toxic cancer treatments while still maintaining maximal therapeutic benefits.