Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer

• Published in: The New England journal of medicine Vol. 372; no. 20; pp. 1909 - 1919
• Main Authors: Mayer, Robert J, Van Cutsem, Eric, Falcone, Alfredo, Yoshino, Takayuki, Garcia-Carbonero, Rocio, Mizunuma, Nobuyuki, Yamazaki, Kentaro, Shimada, Yasuhiro, Tabernero, Josep, Komatsu, Yoshito, Sobrero, Alberto, Boucher, Eveline, Peeters, Marc, Tran, Ben, Lenz, Heinz-Josef, Zaniboni, Alberto, Hochster, Howard, Cleary, James M, Prenen, Hans, Benedetti, Fabio, Mizuguchi, Hirokazu, Makris, Lukas, Ito, Masanobu, Ohtsu, Atsushi
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 14.05.2015
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Cancer therapies; Chemotherapy; Clinical trials; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Double-Blind Method; Drug Combinations; Drug therapy; Evidence-based medicine; Female; Humans; Leukopenia; Life Sciences; Male; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis - drug therapy; Neutropenia; Patients; Proportional Hazards Models; Survival; Survival Analysis; Trifluridine - adverse effects; Trifluridine - therapeutic use; Uracil - adverse effects; Uracil - analogs & derivatives; Uracil - therapeutic use; United States > US; Japan
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1414325

TAS-102, a combination of trifluridine and tipiracil in which tipiracil interferes with the deactivation of trifluridine, improved overall and progression-free survival in patients whose disease had progressed after treatment with fluorouracil-containing drug combinations. Fluoropyrimidines have long represented the cornerstone of treatment for colorectal cancer. 1 Such compounds act primarily as inhibitors of thymidylate synthase, the rate-limiting enzyme in the synthesis of pyrimidine nucleotides. 2 Fluorouracil has been combined with folinic acid (also known as leucovorin) to enhance the capacity of fluorouracil to bind to thymidylate synthase. 2 The addition of irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) to fluorouracil and folinic acid, in combination with either a vascular endothelial growth factor inhibitor (bevacizumab) or an epidermal growth factor inhibitor (e.g., cetuximab or panitumumab) if the tumor contains a wild-type RAS gene, represents contemporary standard therapy and has extended . . .