title: Liver-directed chemotherapy of cetuximab and bevacizumab in combination with oxaliplatin is more effective to inhibit tumor growth of CC531 colorectal rat liver metastases than systemic chemotherapy.
abstract: Colorectal carcinoma is, through to its high rate of liver metastasis (mCRC), the second most cause of cancer death worldwide. Tumor resection represents the only potential cure. In cases of unresectable disease systemic chemotherapy (sCHT) remains the therapy of choice. Modern sCHT regimens including biological agents can induce tumor response that leads to curative surgery of initially unresectable mCRC. However, liver-directed therapy via hepatic arterial infusion (HAI) may produce higher response rates than sCHT. Herein we studied whether a HAI of cetuximab (CE) plus bevacizumab (BE) with or without oxaliplatin (OX) can inhibit tumor growth in a rat model. WAG/Rij rats underwent subcapsular hepatic tumor implantation. After 10 days animals received either HAI or sCHT of CE plus BE, OX or all three drugs. Saline-treated animals served as controls. Tumor growth was estimated at day 10 and 13. On day 13 liver and tumor tissue was studied histologically and immunohistochemically. In controls the tumors grew about 50 %. OX alone was not capable of inhibiting tumor growth. In contrast, CE plus BE given as HAI significantly reduced tumor growth compared to sCHT (p < 0.05). HAI of CE plus BE combined with OX yielded an even more pronounced inhibition of tumor growth. Immunohistochemistry revealed a decreased tumor cell proliferation and tumor vascularization. The present study demonstrates that HAI of CE plus BE is effective to inhibit tumor growth. This effect is even more pronounced in combination with OX. Systemic application of these agents cannot achieve comparable effects.
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, Saarland University Hospital, Homburg/Saar, Germany. jens.sperling@med.uni-goettingen.de
authors.forename: Jens
authors.initials: J
authors.lastname: Sperling
authors.forename: David
authors.initials: D
authors.lastname: Brandhorst
authors.forename: Thilo
authors.initials: T
authors.lastname: Schäfer
authors.forename: Christian
authors.initials: C
authors.lastname: Ziemann
authors.forename: Anna
authors.initials: A
authors.lastname: Benz-Weißer
authors.forename: Claudia
authors.initials: C
authors.lastname: Scheuer
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006499:Hepatic Artery / Q000187:drug effects* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000068818:Cetuximab