Single agent concentrations ranged from 0.1 to 300 microM for 5-FU, CoFactor, and LV. In combined treatment, 5-FU concentration was matched with CoFactor or LV. Sulforodamine B cytotoxic test was used.
CoFactor showed cytotoxic effect on both cell lines. Addition of LV did not change 5-FU cytotoxicity, whereas, the combination of 5-FU with Co- Factor revealed synergistic and add- itive interactions.
LV- or CoFactor- regimens of 5-FU combined with: irinotecan, oxaliplatin, bevacizumab or gemcitabine
A human tumor xenotransplant model for colorectaland pancreatic cancer in athymic nude mice was used as well as an in vivo Balb/c systemic toxicity model.
CoFactor increases the therapeutic index of 5-FU- regimens since it induces equivalent or better antitumor response, less systemic toxicity and less weight loss as compared to LV-containing regimens.
6–8 week old nude mice inoculated subcutaneously with 2 × 106 HT-29 cells.
Combinations of 5-FU, CoFactor, leucovorin, and VEGF (recomb- inant antibody, angiogenesis inhibitor)
When tumors reached 0.1–0.3 cm3 in volume, drugs were administered intraperitoneally. All drugs were dosed daily for 5 consecutive days with the exception of VEGF, dosed on day 1. CoFactor or LV were injected 20 minutes prior to 5-FU.
Mean tumor volumes after Co- Factor/VEGF/5-FU combination we- re smaller than after 5-FU alone, CoFactor/FU, or leucovorin/5-FU. There was greater survival of mice treated with CoFactor/5-FU either with or without VEGF compared to mice treated with only 5-FU.
