Hideaki Bando1, Toshihiko Doi2, Kei Muro3, Hirofumi Yasui4, Tomohiro Nishina5, Kensei Yamaguchi6, Shunji Takahashi7, Shogo Nomura8, Hirofumi Kuno9, Kohei Shitara10, Akihiro Sato11, Atsushi Ohtsu10. 1. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan; Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. Electronic address: tdoi@east.ncc.go.jp. 3. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-0021, Japan. 4. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007, Simo-Nagakubo, Nagaizumi, Shizuoka, 411-8777, Japan. 5. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160, Minami-Umemoto, Matsuyama, Ehime, 791-0280, Japan. 6. Department of Gastroenterology, Saitama Cancer Center, 780, Komuro, Ina, Saitama, 362-0806, Japan; Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. 7. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. 8. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 9. Department of Diagnostic Radiology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 10. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan; Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 11. Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Abstract
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.
RCT Entities:
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.