Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer

Summary

Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.

Timeline

Start

2021-10-01

Primary completion

2022-12-31

Completion

2023-12-01

Publications

• Background Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
• Background Ma J, Yang QL, Ling Y. Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer. BMC Cancer. 2017 Feb 14;17(1):132. doi: 10.1186/s12885-017-3133-8.
• Background Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.
• Background Andersen SE, Andersen IB, Jensen BV, Pfeiffer P, Ota T, Larsen JS. A systematic review of observational studies of trifluridine/tipiracil (TAS-102) for metastatic colorectal cancer. Acta Oncol. 2019 Aug;58(8):1149-1157. doi: 10.1080/0284186X.2019.1605192. Epub 2019 Apr 19.
• Background Wallander M, Rolander B, Avall-Lundqvist E, Elander NO. Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer. J Gastrointest Oncol. 2020 Aug;11(4):616-625. doi: 10.21037/jgo-20-43.
• Background Longo-Munoz F, Argiles G, Tabernero J, Cervantes A, Gravalos C, Pericay C, Gil-Calle S, Mizuguchi H, Carrato-Mena A, Limon ML, Garcia-Carbonero R. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial. Clin Transl Oncol. 2017 Feb;19(2):227-235. doi: 10.1007/s12094-016-1528-7. Epub 2016 Jul 21.
• Background Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. doi: 10.1056/NEJMoa1414325.
• Background Yoshida Y, Yamada T, Matsuoka H, Sonoda H, Fukazawa A, Yoshida H, Ishida H, Hirata K, Hasegawa S, Sakamoto K, Otsuka T, Koda K. A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study). J Anus Rectum Colon. 2019 Jul 30;3(3):136-141. doi: 10.23922/jarc.2018-043. eCollection 2019.
• Background Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9.
• Background Liu H, Ma Y, Xu HC, Huang LY, Zhai LY, Zhang XR. Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept. Curr Eye Res. 2020 Dec;45(12):1467-1476. doi: 10.1080/02713683.2020.1781193. Epub 2020 Jul 7.
• Background Kotani D, Kuboki Y, Horasawa S, Kaneko A, Nakamura Y, Kawazoe A, Bando H, Taniguchi H, Shitara K, Kojima T, Tsuji A, Yoshino T. Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer. BMC Cancer. 2019 Dec 27;19(1):1253. doi: 10.1186/s12885-019-6475-6.
• Background Eriksson T, Bjorkman S, Roth B, Fyge A, Hoglund P. Enantiomers of thalidomide: blood distribution and the influence of serum albumin on chiral inversion and hydrolysis. Chirality. 1998;10(3):223-8. doi: 10.1002/(SICI)1520-636X(1998)10:33.0.CO;2-A.
• Background Zhang L, Qu X, Teng Y, Shi J, Yu P, Sun T, Wang J, Zhu Z, Zhang X, Zhao M, Liu J, Jin B, Luo Y, Teng Z, Dong Y, Wen F, An Y, Yuan C, Chen T, Zhou L, Chen Y, Zhang J, Wang Z, Qu J, Jin F, Zhang J, Jin X, Xie X, Wang J, Man L, Fu L, Liu Y. Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study). J Clin Oncol. 2017 Nov 1;35(31):3558-3565. doi: 10.1200/JCO.2017.72.2538. Epub 2017 Aug 30.
• Background Melchert M, List A. The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. doi: 10.1016/j.biocel.2007.01.022. Epub 2007 Jan 30.
• Background Chen C, Yu G, Xiao W, Xing M, Ni J, Wan R, Hu G. Thalidomide inhibits proliferation and epithelial-mesenchymal transition by modulating CD133 expression in pancreatic cancer cells. Oncol Lett. 2017 Dec;14(6):8206-8212. doi: 10.3892/ol.2017.7213. Epub 2017 Oct 18.
• Background 中国临床肿瘤学会（CSCO）.抗肿瘤治疗相关恶心呕吐预防和治疗指南（M）.（2019.V1.0）

Drugs

Indications