Takayuki Yoshino1, Hiroyuki Uetake2, Yuya Funato3, Yasunobu Yamaguchi3, Takahiko Koyama3, Daisuke Ozawa3, Masaru Tajiri3, Kei Muro4. 1. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan. 2. Department of Specialized Surgeries, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. 3. Taiho Pharmaceutical Co., Ltd, Tokyo, Japan. 4. Department of Clinical Oncology and Outpatient Treatment Center, Aichi Cancer Center Hospital, Aichi, Japan.
Abstract
BACKGROUND: The novel oral nucleoside antineoplastic agent trifluridine/tipiracil was approved for metastatic colorectal cancer in Japan in March 2014. In this post-marketing surveillance study, we investigated the safety and efficacy of trifluridine/tipiracil in a real-world setting, particularly haematological drug reactions classified according to the baseline renal and hepatic functions. METHODS: We investigated patients with metastatic colorectal cancer who received trifluridine/tipiracil during the first four treatment cycles prospectively. The patients typically received 35 mg/m2 trifluridine/tipiracil twice daily on days 1-5 and 8-12 every 28 days. The primary objective was to assess the safety of trifluridine/tipiracil, but its efficacy was also evaluated. RESULTS: Between July 2014 and June 2016, 860 patients were enrolled in the study, and the safety and efficacy of trifluridine/tipiracil were evaluated in 823 patients. Adverse drug reactions occurred in 89.7% of the patients. The most common adverse drug reactions were decreased white blood cell count (67.0%) and neutrophil count (63.9%). Haematological drug reactions of grade ≥3 were observed in 41.7% of the patients with normal renal function; 50.3, 65.6 and 78.9% of the patients had mild, moderate and severe renal impairments, respectively. Hepatic impairment was not associated with a higher incidence of haematological drug reactions. The median overall survival was 8.4 months, with a 1-year survival rate of 33.7%. CONCLUSION: This post-marketing surveillance study further confirmed the safety and tolerability profile of trifluridine/tipiracil observed in a clinical study setting.
BACKGROUND: The novel oral nucleoside antineoplastic agent trifluridine/tipiracil was approved for metastatic colorectal cancer in Japan in March 2014. In this post-marketing surveillance study, we investigated the safety and efficacy of trifluridine/tipiracil in a real-world setting, particularly haematological drug reactions classified according to the baseline renal and hepatic functions. METHODS: We investigated patients with metastatic colorectal cancer who received trifluridine/tipiracil during the first four treatment cycles prospectively. The patients typically received 35 mg/m2 trifluridine/tipiracil twice daily on days 1-5 and 8-12 every 28 days. The primary objective was to assess the safety of trifluridine/tipiracil, but its efficacy was also evaluated. RESULTS: Between July 2014 and June 2016, 860 patients were enrolled in the study, and the safety and efficacy of trifluridine/tipiracil were evaluated in 823 patients. Adverse drug reactions occurred in 89.7% of the patients. The most common adverse drug reactions were decreased white blood cell count (67.0%) and neutrophil count (63.9%). Haematological drug reactions of grade ≥3 were observed in 41.7% of the patients with normal renal function; 50.3, 65.6 and 78.9% of the patients had mild, moderate and severe renal impairments, respectively. Hepatic impairment was not associated with a higher incidence of haematological drug reactions. The median overall survival was 8.4 months, with a 1-year survival rate of 33.7%. CONCLUSION: This post-marketing surveillance study further confirmed the safety and tolerability profile of trifluridine/tipiracil observed in a clinical study setting.