Your browser doesn't support javascript.
loading
Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry.
Lee, James J; Seraj, Jabed; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Strychor, Sandra; Fiejdasz, Jillian; Faulkner, Tyeler; Parise, Robert A; Fawcett, Patrick; Pollice, Laura; Mason, Scott; Hague, Jeremy; Croft, Marie; Nugteren, James; Tedder, Charles; Sun, Weijing; Chu, Edward; Beumer, Jan Hendrik.
Affiliation
  • Lee JJ; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Suite G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
  • Seraj J; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Yoshida K; Taiho Oncology Inc., Princeton, NJ, USA.
  • Mizuguchi H; Taiho Oncology Inc., Princeton, NJ, USA.
  • Strychor S; Taiho Oncology Inc., Princeton, NJ, USA.
  • Fiejdasz J; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Suite G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
  • Faulkner T; Clinical Research Services, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Parise RA; Clinical Research Services, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Fawcett P; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Suite G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
  • Pollice L; Clinical Research Services, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Mason S; Clinical Research Services, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
  • Hague J; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Croft M; Xceleron Inc., Germantown, MD, USA.
  • Nugteren J; Xceleron Inc., Germantown, MD, USA.
  • Tedder C; Xceleron Inc., Germantown, MD, USA.
  • Sun W; INC Research LLC, Raleigh, NC, USA.
  • Chu E; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Suite G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
  • Beumer JH; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Cancer Chemother Pharmacol ; 77(3): 515-26, 2016 Mar.
Article in En | MEDLINE | ID: mdl-26787503
ABSTRACT

BACKGROUND:

TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 10.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD.

METHODS:

Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [(14)C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [(14)C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h and were analyzed for (14)C by accelerator mass spectrometry and analytes by LC-MS/MS.

RESULTS:

FTD 59.8% of the (14)C dose was recovered 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI 76.8% of the (14)C dose was recovered 27.0% in urine mostly as TPI and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI.

CONCLUSION:

Absorbed (14)C-FTD was metabolized and mostly excreted in urine. The majority of (14)C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyrimidines / Uracil / Trifluridine / Neoplasms / Antineoplastic Agents Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Cancer Chemother Pharmacol Year: 2016 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyrimidines / Uracil / Trifluridine / Neoplasms / Antineoplastic Agents Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Cancer Chemother Pharmacol Year: 2016 Document type: Article Affiliation country: United States