Bevacizumab and cetuximab with conventional chemotherapy reduced pancreatic tumor weight in mouse pancreatic cancer xenografts

Clin Exp Med. 2017 May;17(2):141-150. doi: 10.1007/s10238-016-0409-2. Epub 2016 Mar 19.

Abstract

Pancreatic cancer remains the fourth leading cause of cancer-related death in the USA with a 5-year survival rate of 5 %. The effects of epidermal growth factor receptor and vascular endothelial growth factor A blockade with chemotherapy on pancreatic tumor growth were examined. Mice bearing human PANC-1 cell xenografts were divided into three groups: T-CR (gemcitabine, cisplatin, and 5-fluorouracil), T-TR (cetuximab, bevacizumab, gemcitabine, cisplatin, and 5-fluorouracil), and vehicle control (T). The therapies were administered via intraperitoneal injections every 4 days for seven cycles from 7 weeks after cancer cell implantation. Mice treated with T-TR had significant reductions in tumor weight as compared to the control group (p < 0.05). Although mice in the T-CR group experienced a significant reduction in body weight gain, serum albumin, and gastrocnemius muscle mass (p < 0.05), no such reductions were observed in the T-TR group. Mice treated with T-TR had slightly increased CD11c+ DC and CD49b+ NK cell levels in the spleen (p < 0.05) and significantly lower tumor VEGF expression (p < 0.05). Tumor carcinoembryonic antigen expression was significantly reduced in both treatment groups (p < 0.05). Thus, addition of bevacizumab and cetuximab to gemcitabine, cisplatin, and fluorouracil may represent an effective treatment option for pancreatic cancer that warrants further study.

Keywords: 5-Fluorouracil; Bevacizumab; Cetuximab; Cisplatin; Gemcitabine; Pancreatic cancer; Xenograft.

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Bevacizumab / administration & dosage*
  • Cetuximab / administration & dosage*
  • Disease Models, Animal
  • Drug Therapy / methods*
  • Drug Therapy, Combination / methods
  • Female
  • Heterografts
  • Humans
  • Mice, Inbred BALB C
  • Pancreatic Neoplasms / drug therapy*
  • Treatment Outcome
  • Tumor Burden

Substances

  • Antineoplastic Agents, Immunological
  • Bevacizumab
  • Cetuximab