Low-dose warfarin prophylaxis for catheter-associated thrombosis in cancer patients. Can it be safely associated with 5-Fluorouracil-based chemotherapy?

The Oncologist 2004;9:596 www.TheOncologist.com Correspondence: David J. Kuter, M.D., D. Phil., Hematology Unit, COX 640, Massachusetts General Hospital, 100 Blossom Street, Boston, Massachusetts 02114, USA. Telephone: 617-726-3908; Fax: 617-724-3166; e-mail: kuter.david@MGH. harvard.edu Received July 15, 2004; accepted for publication July 23, 2004. ©AlphaMedPress 1083-7159/2004/$12.00/0 I agree with the comments made in the letter by Magagnoli et al. regarding the increased likelihood of an increased International Normalized Ratio (INR) and possible bleeding when low-dose warfarin is used in patients with 5-fluorouracil (5-FU)-based chemotherapy regimens. 5-FU seems to inhibit the metabolism of the more active Senantiomer of warfarin, decrease its clearance, and thereby enhance the hypoprothrombinemic effect of warfarin [1]. Indeed, in patients on full-dose warfarin who subsequently receive 5-FU, the average warfarin dose to maintain a therapeutic INR declines by nearly half and requires careful weekly monitoring [2]. Similar effects have been noted with capecitabine (Xeloda®; Roche Laboratories, Inc.; Nutley, NJ), the prodrug of 5-FU [3, 4]. It is for reasons such as this, as well as the lack of any demonstrable benefit of low-dose warfarin in clinical trials of catheter prophylaxis, that I personally do not use or recommend low-dose warfarin catheter prophylaxis. For patients with marginal nutrition or impaired hepatic function or who are on 5-FU or capecitabine chemotherapy regimens, I would certainly not recommend low-dose warfarin prophylaxis. However if low-dose prophylaxis is used in those settings, weekly INR monitoring is strongly recommended. The Oncologist Letter to the Editor