ISR Failure for 5-Fluorouracil Analysis from Patients Dosed with Capecitabine

Capecitabine (Xeloda, Roche) is an orally-administered chemotherapy agent for treating breast and colorectal cancers. Capecitabine is a prodrug which is enzymatically converted to the active drug 5-fluorouracil (5-FU) within the tumor. 5-Fluorouracil (Adrucil, Teva Generics) is administered by infusion and inhibits action of the enzyme, thymidylate synthase (required for DNA replication) which causes cancerous cells to undergo cell death. It is used to treat breast, colorectal, stomach, pancreatic and skin cancers. A clinical study involved the measurement of 5-FU from patients who were dosed orally with capecitabine and from patients dosed by infusion with 5-FU. ISR analysis for 5-fluorouracil on samples from patients that were dosed orally with capecitabine failed this evaluation while 5-FU IV dosed patients in the same study had acceptable ISR results, shown at right.