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

European Journal of Cancer, July 2016, Pages 46 - 53

Abstract

Aim

American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m2 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/m2 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/m2 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/m2 b.i.d. schedule.

Results

Twenty-nine patients were assessable after completing the 35 mg/m2 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/m2 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

Highlights

  • We evaluated TAS-102 among Japanese patients with advanced gastric cancer (AGC).
  • TAS-102 (35 mg/m2 twice a day) provided a disease control rate of 65.5% for AGC.
  • The progression-free and overall survivals were 2.9 and 8.7 months.
  • There were no gastric cancer-specific toxicities or complications.
  • A randomised double-blind phase III study is ongoing to validate our findings.

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

Footnotes

a Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

b Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

c Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-0021, Japan

d Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007, Simo-Nagakubo, Nagaizumi, Shizuoka, 411-8777, Japan

e Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160, Minami-Umemoto, Matsuyama, Ehime, 791-0280, Japan

f Department of Gastroenterology, Saitama Cancer Center, 780, Komuro, Ina, Saitama, 362-0806, Japan

g Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan

h Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan

i Biostatistics Division, Center for Research Administration and Support, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

j Department of Diagnostic Radiology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

Corresponding author. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. Tel.: +81 4 7133 1111; fax: +81 4 7134 6928.

This study was supported by a grant from the Renovation Project of Early and Exploratory Clinical Trial Center, National Cancer Center Research and Development Fund (24-A-1). Taiho Pharmaceutical Company provided the study drugs and performed the PK analyses.