CLINICAL AND PHARMACOKINETIC EFFECTS OF COMBINED WARFARIN AND 5-FLUOROURACIL IN ADVANCED COLON CANCER

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (11) , 4827-4830
Abstract
Patients (25) with advanced, measurable adenocarcinoma of the colon were treated with 5-fluorouracil (FUra), 15-20 mg/kg per wk i.v., plus warfarin p.o. [per os], at a dosage which maintains therapeutic levels of anticoagulation. Of the patients, 64% achieved either objective response (20%) or stable disease (44%). Overall median survival was 19.2 mo. Three patients (all with intraluminal lesions) developed gastrointestinal blood loss requiring transfusion and discontinuation of anticoagulation. The interaction between warfarin and FUra, as measured by plasma levels, was investigated in 7 rabbits and 3 patients. Plasma samples were obtained for 2 h after FUra administration, both before and after anticoagulation with warfarin. FUra was measured by gas chromatography, and warfarin was assayed using a TLC fluorescence method. In rabbits, prolongation of FUra plasma t1/2 [half-life] was seen with high (0.6 mg/kg per h), but not low (0.025 mg/kg per h), rates of warfarin infusion. In patients, FUra t1/2 was not changed by therapeutic warfarin anticoagulation. Plasma clearance interaction between FUra and warfarin does not occur in patients receiving therapeutic levels of anticoagulation. FUra and warfarin anticoagulation can be safely given and frequently result in stable disease status for patients with advanced colon cancer. Further trials of this combination are warranted in adenocarcinomas of the colon.