Oral recombinant methioninase combined with oxaliplatin and 5-fluorouracil regressed colon cancer growing on the peritoneal surface in a patient-derived orthotopic xenograft mouse model

Abstract The aim of this study was to determine the efficacy of oral recombinant methioninase (o-rMETase) on a model of colon cancer growing on the peritoneal surface using a patients-derived orthotopic xenograft (PDOX) nude mouse model. Forty colon cancer growing on the peritoneum PDOX mouse models were divided into 4 groups of 10 mice each by measuring the tumor size and fluorescent intensity: untreated control; 5-fluouracil (5-FU) and oxaliplatin (OXA) (50 mg/kg, 6 mg/kg, once a week for two weeks); o-rMETase (100 units/day, oral 14 consecutive days); combination 5-FU + OXA and o-rMETase. All treatments inhibited tumor growth compared to the untreated control. The combination of 5-FU + OXA plus o-rMETase was significantly more efficacious than the control and each drug alone and was the only treatment that caused tumor regression. The present study is the first demonstrating the efficacy of o-rMETase combination therapy on a PDOX model of peritoneal colon cancer, suggesting potential clinical development of o-rMETase in a recalcitrant cancer.