A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201)

Eur J Cancer. 2016 Jul;62:46-53. doi: 10.1016/j.ejca.2016.04.009. Epub 2016 May 19.


Aim: American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m(2) twice a day (b.i.d.), although this schedule did not provide clinically relevant improvements in a phase II study of advanced gastric cancer (AGC). However, a pivotal phase III study revealed that TAS-102 at 35 mg/m(2) b.i.d. provided a clinically relevant improvement in overall survival (OS) among patients with metastatic colorectal cancer. Therefore, we re-evaluated the efficacy, safety, and pharmacokinetic parameters of TAS-102 at 35 mg/m(2) b.i.d among Japanese patients with AGC.

Methods: All patients had undergone one or two previous chemotherapy regimens that contained fluoropyrimidine, platinum agents, and taxanes or irinotecan. The primary end-point target was a disease control rate (DCR) of ≥50% after 8 weeks of the 35 mg/m(2) b.i.d. schedule.

Results: Twenty-nine patients were assessable after completing the 35 mg/m(2) b.i.d. schedule. The investigator-determined DCR was 65.5% (95% confidence interval [CI], 45.7-82.1%) and the independent central review's DCR was 51.9% (95% CI, 31.9-71.3%); both results exceeded the primary end-point target. The median progression-free survival and OS were 2.9 months (95% CI, 1.1-5.3 months) and 8.7 months (95% CI, 5.7-14.9 months), respectively. The grade III/IV adverse events included neutropenia (69.0%), leucopaenia (41.4%), anaemia (20.7%), and anorexia (10.3%). No AGC-specific toxicities were detected.

Conclusions: The 35 mg/m(2) b.i.d. dose of TAS-102 provided positive efficacy and an acceptable toxicity profile in patients with AGC. A randomised, double-blind, placebo-controlled, phase III study is ongoing to validate these findings.

Clinical trial registration number: UMIN000007421.

Trial registration: ClinicalTrials.gov NCT02500043.

Keywords: Efficacy; Gastric cancer; Monotherapy; Pharmacokinetic parameters; Phase II clinical trial; Safety; TAS-102.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pyrrolidines
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Thymine
  • Trifluridine / administration & dosage
  • Trifluridine / adverse effects
  • Trifluridine / pharmacokinetics
  • Trifluridine / therapeutic use*
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / pharmacokinetics
  • Uracil / therapeutic use


  • Drug Combinations
  • Pyrrolidines
  • trifluridine tipiracil drug combination
  • Uracil
  • Thymine
  • Trifluridine

Associated data

  • ClinicalTrials.gov/NCT02500043