P1-210Fluoropyrimidine-based chemotherapy for gastrointestinal cancer in patients with direct oral anticoagulants or warfarin

Abstract Background The warfarin is known to enhance its activity by interaction with fluoropyrimidine. On the other hands, direct oral anticoagulants (DOACs) have several advantages compared with warfarin such as the unnecessity of dose monitoring and their few drug interactions. Therefore, the aim of this study is to assess the dose intensity and safety of fluoropyrimidine-based chemotherapy for gastrointestinal cancer in patients with DOACs or warfarin. Methods Between January 2006 to June 2018, a total of 1,413 patients with esophageal, gastric, colorectal, and pancreatic cancer received fluoropyrimidine-based chemotherapy at two institutions. Among all patients, 49 patients with anticoagulant therapy were enrolled in this study. They were further divided into the warfarin group (27 patients) and the DOACs group (22 patients). We retrospectively analyzed their Relative Dose Intensity (RDI) of fluoropyrimidine, Time in Therapeutic Range (TTR) of warfarin, and bleeding or thrombosis events. Results In the warfarin group, the median RDI of fluoropyrimidne and TTR of warfarin was 80.0% (0-100%) and 37.5% (0-100%), respectively. The proportion of patients with prolonged PT-NR values (cut off value of 3.00) was 51.9% (14/27). In the DOACs group, the median RDI was 72.9% (0-100%). There was no significant difference in RDI (p = 0.88), although TTR of warfarin was relatively low. The bleeding or thrombosis events occurred only in the warfarin group (3.7% and 7.4%, respectively). Conclusions This study showed the RDI of fluoropyrimidine in the DOACs group was sufficient compared with the warfarin group. However, major bleeding and thrombosis events, which seemed to be related with low TTR of warfarin, occurred only in the warfarin group. These data may suggest that DOACs are recommended as better anti-coagulation agents than warfarin during chemotherapies using fluoropyrimidine for gastrointestinal cancer.