TAS-102 is a novel oral
nucleoside antitumor agent consisting of
trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5.
TAS-102 was approved in Japan in March 2014 for the treatment of patients with unresectable, advanced or recurrent
colorectal cancer that is refractory to standard
therapies. In the present study, enhancement of the therapeutic efficacy using a combination
therapy of
TAS-102 and
irinotecan hydrochloride (CPT-11) was evaluated in a colorectal and
gastric cancer xenograft-bearing nude mouse model.
TAS-102 was orally administered twice a day from day 1 to 14, and
CPT-11 was administered intravenously on days 1 and 8. The growth-inhibitory activity was evaluated based on the
tumor volume and the growth-delay period, which was estimated based on the period required to reach a
tumor volume that was five-times greater than the initial volume (RTV5). The
tumor growth-inhibitory activity and the RTV5 of the group receiving
TAS-102 with
CPT-11 were significantly superior to those of both agents as monotherapy for mice with KM12C, KM12C/5-FU, DLD-1/5-FU, and SC-2 xenografts (p<0.01). No significant decrease in
body weight was observed. The present pre-clinical findings indicated that the combination of
TAS-102 and
CPT-11 is a promising treatment option for colorectal or
gastric cancer, not only for chemo-naïve
tumors, but also for recurrent
tumors after
5-fluorouracil (5-FU)-based
chemotherapy.