Combination of Trabectedin With Oxaliplatinum and 5-Fluorouracil Arrests a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model.

Abstract

In the present study, we aimed to determine the efficacy of trabectedin (TRAB) combined with oxaliplatinum (OXA)+5-fluorouracil (5-FU) on a colorectal cancer (CRC) patient-derived orthotopic xenograft (PDOX) mouse model. A patient CRC tumor previously established in nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice. Harvested tumor fragments were transplanted orthotopically in non-transgenic nude mice. Mice were randomized into three groups: Group 1 (G1), untreated-control; Group 2 (G2), OXA+5-FU; Group 3 (G3), TRAB+OXA+5-FU. Tumor width, length, and mouse body weight were measured twice a week. Both treatment groups inhibited tumor growth compared to the untreated control group. The combination of TRAB, OXA and 5-FU was significantly more efficacious than OXA+5-FU and arrested tumor growth. No significant changes were observed in body-weight in any of the three groups. TRAB, OXA and 5-FU combination has clinical potential for this and other CRC patients.