生物活性

• 描述Trifluridine have been widely used for the treatment of multiple neoplasms. But trifluridine is rapidly degraded to an inactive metabolite by thymidine phosphorylase making its poor bioavailability. Tipiracil HCl, a potent and specific chemical inhibitor of thymidine phosphorylase, creates an opportunity to improve the PK properties of trifluridine. Trifluridine/tipiracil (TAS-102) is a new orally active antineoplastic agent comprised of trifluridine and tipiracil in a molar ratio of 1:0.5. Compared with trifluridine alone, the coadministration of oral trifluridine and tipiracil in mice and monkeys led to an increased bioavailability of trifluridine and a marked increase in the trifluridine area under the concentration–time curve (AUC) and maximum observed plasma concentration (C_max). The global phase 3 RECOURSE trial showed that, compared with a placebo control, trifluridine/tipiracil increased overall survival in patients with refractory metastatic colorectal cancer by 1.8 months^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02743221	Metastatic Colorectal Cancer	Phase 2	Active, not recruiting	October 2019	-
  NCT03297710	Rectal Adenocarcinoma ... more >> Recurrent Rectal Carcinoma Stage IV Rectal Cancer AJCC v7 Stage IVA Rectal Cancer AJCC v7 Stage IVB Rectal Cancer AJCC v7 Collapse <<	Phase 1	Recruiting	October 31, 2019	United States, Arizona ... more >> Mayo Clinic in Arizona Recruiting Scottsdale, Arizona, United States, 85259 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Daniel H. Ahn          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Joleen M. Hubbard Collapse <<
  NCT02848443	Metastatic Colorectal Cancer	Phase 1	Recruiting	December 2019	Austria ... more >> Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie Recruiting Wien, Austria France CHU Timone Recruiting Marseille, France Hôpital Saint Antoine Recruiting Paris, France Hôpital Universitaire Pitié Salpêtrière - Pavillon Antonin Gosset Recruiting Paris, France Centre Eugène Marquis Recruiting Rennes, France HIA Bégin Recruiting Saint Mandé, France Gustave Roussy Recruiting Villejuif, France Germany St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum Abteilung für Hämatologie und Onkologie Recruiting Bochum, Germany Universitaetsklinikum Hamburg-Eppendorf Hubertus Wald Tumorzentrum - UCCH Recruiting Hamburg, Germany Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III Recruiting Munchen, Germany Universitätsklinikum Ulm, Zentrum für Innere Medizin, Klinik für Innere Medizin I Recruiting Ulm, Germany Klinikum Wolfsburg, Medizinische Klinik II Recruiting Wolfsburg, Germany Hungary Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly Recruiting Budapest, Hungary Orszagos Onkologiai Intezet "B" Belgyogyaszati-Onkologiai O. Es Klin. Farmakologiai O. Recruiting Budapest, Hungary Semmelweis Egyetem, I. sz. Belgyogyaszati Klinika - Klin. Farmakologiai Reszleg Recruiting Budapest, Hungary Italy ARNAS - Azienda Ospedaliera Garibaldi - Nesima Struttura Complessa di Oncologia Medica Recruiting Catania, Italy Ist.Scientifico Romagnolo per lo Studio e la Cura dei Tumori Department of Clinical Oncology Recruiting Meldola, Italy Poiclinico G.B. Rossi A.O.U.I. di Verona Recruiting Verona, Italy Spain ICO Badalona. H. Germans Trials y Pujol, Servicio de Oncología médica Recruiting Badalona, Spain Hospital Vall D'Hebron (VHIO) Recruiting Barcelona, Spain HOSPITAL UNIVERSITARIO GREGORIO MARAÑON Oncología Médica Recruiting Madrid, Spain Hospital Universitario Madrid Sanchinarro Recruiting Madrid, Spain Hospital Universitario Ramón y Cajal de Madrid Recruiting Madrid, Spain Hospital Clinico de Valencia Recruiting Valencia, Spain United Kingdom Christie Hospital NHS Foundation Trust GI & Endocrine Recruiting Manchester, United Kingdom Collapse <<

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• 参考文献

• [1] Peters GJ, Bijnsdorp IV. TAS-102: more than an antimetabolite. Lancet Oncol.2012 Dec;13(12):e518-9.

  [2] Yoshino T, Mizunuma N, et al. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2012 Oct;13(10):993-1001.

  [3] A Phase 1 Study of the Pharmacokinetics of Nucleoside Analog Trifluridine and Thymidine Phosphorylase Inhibitor Tipiracil (Components of TAS-102) vs Trifluridine Alone