The in vivo combination effect of
AC-7700, a novel
combretastatin A-4 derivative, and
cisplatin (CDDP) was examined. The combination of
AC-7700 and CDDP increased antitumor activity against murine colon 26
tumor in mice and cured the mice. This combination effect was found over wide dosage ranges of
AC-7700 (20-80 mg/kg) and CDDP (2.5-5 mg/kg). Moreover, this combination augmented antitumor activity against murine S180 and M109
tumors, and human LX-1 and LS180
tumor xenografts in mice. The effect was the strongest when
AC-7700 and CDDP were administered simultaneously. To study this combination effect, we measured the concentrations of CDDP in
tumors, plasma and kidneys of the mice with colon 26
tumor. In the combination with
AC-7700, the concentration of CDDP in the
tumors increased from 0.5 to 96 h after administration, but did not change or decrease in plasma or kidneys. Against human LS180 xenografts in mice, the combination similarly increased the concentration of CDDP in the
tumors. These results suggest that
AC-7700 may specifically augment the accumulation of CDDP in
tumors, and thus has the potential to be useful in
combination chemotherapy with CDDP.