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Integrated safety summary for trifluridine/tipiracil (TAS-102)

Falcone, Alfredoa; Ohtsu, Atsushic; Van Cutsem, Erice; Mayer, Robert, J.f; Buscaglia, Micheleb; Bendell, Johanna, C.g; Kopetz, Scotth; Bebeau, Pauli; Yoshino, Takayukid

doi: 10.1097/CAD.0000000000000554

Trifluridine/tipiracil, an oral treatment combining trifluridine (an antineoplastic thymidine-based nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor), led to significant improvement in overall survival in metastatic colorectal cancer (mCRC) patients refractory to standard therapy in the phase III RECOURSE trial. Here, we report an integrated summary of the safety of trifluridine/tipiracil. The main safety analysis includes integrated data from the RECOURSE and J003 studies (safety data group 2) of patients with refractory mCRC receiving trifluridine/tipiracil at the recommended starting dose: 35 mg/m2 twice daily for 5 days with 2 days’ rest for 2 weeks, followed by a 14-day rest (one cycle). Integrated data from a larger group of mCRC patients receiving trifluridine/tipiracil at the recommended starting dose (group 1) and nonintegrated data on serious adverse events (SAEs) representing all clinical experience with trifluridine/tipiracil as of the data cutoff date (group 3) are also summarized. In group 2, myelosuppressive and all-grade gastrointestinal adverse events (AEs) were more frequent in trifluridine/tipiracil patients than in placebo patients. The trifluridine/tipiracil and placebo patients had similar frequencies of AEs leading to discontinuation (9.0 vs. 11.5%) and SAEs (27.7 vs. 29.2%); fatal AEs were more frequent in placebo patients than in trifluridine/tipiracil patients (9.3 vs. 2.8%). AEs leading to interruptions/delays/reductions were more frequent in trifluridine/tipiracil patients (56.3 vs. 12.7%). Trifluridine/tipiracil was generally well tolerated, but over 50% of patients required interruptions/delays/reductions. There was a low rate of discontinuations, SAEs, and fatal AEs. This analysis confirms the safety profile observed in RECOURSE.

aDepartment of Oncology and the Specialization School, Pisana University Hospital, University of Pisa, Pisa

bRadiodynamics Service, IRCCS AOU San Martino IST, Genoa, Italy

cDepartment of GI Oncology/Gastroenterology

dDivision of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

eDigestive Oncology Unit, University Hospitals Leuven, Leuven, Belgium

fCenter for Gastrointestinal Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

gGI Oncology Research, Development Unit, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Tennessee

hDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas

iPharmacovigilance, Taiho Oncology, Inc., Princeton, New Jersey, USA

Correspondence to Alfredo Falcone, MD, Pisana University Hospital, University of Pisa, Via Roma, 67, 56126 Pisa, Italy Tel: +39 050 993064; fax: +39 050 992069;e-mail:

Received June 19, 2017

Accepted August 2, 2017

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