Mass balance study of TAS-102 using 14C labeling analyzed by accelerator mass spectrometry.

2563 Background: TAS-102 is composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 2:1 ratio. FTD is a thymidine analog, and is degraded to inactive trifluoromethyluracil (FTY) by thymidine phosphorylase (TPase). TPI inhibits degradation of FTD by TPase, increasing systemic exposure to FTD. TAS-102 demonstrated improvement in overall survival in patients with metastatic colorectal cancer refractory to standard therapies. Although the metabolism of FTD has been reported, the metabolic fate and excretion of TAS-102 is unknown. Methods: Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) enrolled. Group A (N = 4) received 60 mg TAS-102 with 200 nCi [14C]-FTD, and group B (N = 4) received 60 mg TAS-102 with 1000 nCi [14C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h, and were analyzed for 14C by accelerator mass spectrometry and for components of TAS-102 by LC-MS/MS. Results: FTD: Approximately 10% of plasma 14C AUC is...