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.