Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf®, Princeton, NJ, USA) 
is a combination tablet of trifluridine, a thymidine-based nucleoside analog, 
and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This 
drug was first approved for use in metastatic colorectal cancer patients. 
Recently, the U S Food and Drug Administration (FDA) and the European Medicines 
Agency (EMA) have granted approval of trifluridine/tipiracil for treatment of 
metastatic gastric and gastroesophageal junction adenocarcinoma in patients 
following at least two lines of chemotherapy including fluoropyrimidine and 
platinum chemotherapy agents, as well as taxanes or irinotecan. This approval 
was granted after the findings from first a Phase II trial (EPOC1201) 
investigating trifluridine/tipiracil, and later a global Phase III trial (TAGS 
trial) that compared trifluridine/tipiracil vs placebo with best supportive 
care. Both trials primarily utilized trifluridine/tipiracil at a dose of 35 
mg/m2 twice daily. In the EPOC1201 trial, the primary end point of disease 
control rate was greater than 50% after eight weeks of therapy. The most common 
grade three or four adverse event was neutropenia; additional toxicities 
included leukopenia, anemia, and anorexia. In the TAGS trial, overall survival 
in patients treated with trifluridine/tipiracil (5.7 months) was significantly 
improved as compared to the placebo-controlled group (3.6 months). Treatment 
with trifluridine/tipiracil not only did not impair quality of life but also 
tended to reduce the risk of deterioration of quality of life. The results of 
these studies along with the subsequent FDA and EMA approval have generated an 
important breakthrough in regard to treatment options for patients with 
refractory metastatic gastric or gastroesophageal junction adenocarcinoma.