RRC ID 38127
Author Nukatsuka M, Nakagawa F, Takechi T.
Title Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, TAS-102, with Oxaliplatin on Human Colorectal and Gastric Cancer Xenografts.
Journal Anticancer Res.
Abstract TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine (FTD) and the thymidine phosphorylase inhibitor tipiracil hydrochloride (at a molar ratio of 1:0.5) that was approved in Japan in 2014 for the treatment of unresectable advanced or recurrent colorectal cancer. In the present study, the enhancement of therapeutic efficacy using a combination of TAS-102 and oxaliplatin was evaluated in a xenograft-bearing nude mouse model of colorectal and gastric cancer. TAS-102 was orally administered twice-a-day from day 1 to 14, and oxaliplatin was administered intravenously on days 1 and 8. The in vivo growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, was estimated based on the period required to reach a tumor volume five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and RTV5 in mice administered TAS-102 with oxaliplatin were significantly superior to those associated with either monotherapy in mice with colorectal (HCT 116, SW-48; p<0.001) and gastric cancer (SC-2, MKN74; p<0.001). MKN74/5FU, a 5-fluorouracil-resistant MKN74 sub-line, was sensitive to both FTD and oxaliplatin in vitro. In vivo, TAS-102 alone was effective in MKN74/5FU, and its anti-tumor activity was significantly enhanced in combination with oxaliplatin (p<0.001). No significant decrease in body weight or toxicity was observed compared to either monotherapy. The present pre-clinical findings indicate that combination of TAS-102 and oxaliplatin is a promising treatment option for colorectal or gastric cancer, and can be utilized in both chemo-naïve tumors and recurrent tumors after 5-fluorouracil treatment.
Volume 35(9)
Pages 4605-15
Published 2015-9
PII 35/9/4605
PMID 26254349
MeSH Administration, Oral Animals Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Antineoplastic Combined Chemotherapy Protocols / pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Body Weight / drug effects Cell Death / drug effects Cell Proliferation / drug effects Colorectal Neoplasms / drug therapy* Colorectal Neoplasms / pathology Drug Combinations HCT116 Cells Humans Mice, Nude Organoplatinum Compounds / pharmacology Organoplatinum Compounds / therapeutic use* Oxaliplatin Stomach Neoplasms / drug therapy* Stomach Neoplasms / pathology Treatment Outcome Trifluridine / administration & dosage Trifluridine / pharmacology Trifluridine / therapeutic use* Tumor Burden / drug effects Uracil / administration & dosage Uracil / analogs & derivatives* Uracil / pharmacology Uracil / therapeutic use Xenograft Model Antitumor Assays*
IF 1.865
Times Cited 7
Human and Animal Cells MKN74(RCB1002)