Phase 1 drug interaction study of suramin and warfarin in patients with prostate cancer

Potential interaction between suramin and warfarin was evaluated when coadm inistered to patients with cancer. Thirteen men with advanced hormone-refra ctory prostate cancer were initially stabilized with warfarin to a prothrom bin time (PT) of 2 +/- 0.2 International Normalized Ratio (INR) during a le ad-in period of 4 weeks, A baseline daily warfarin dose was established, an d treatment with suramin plus hydrocortisone was then started; The effect o f suramin on the anticoagulant activity of warfarin was assessed in each pa tient by comparing his baseline warfarin dose with average daily doses requ ired to maintain the same INR level over each of the initial 6 weeks of a 1 2-week course of suramin treatment. The average daily dose of warfarin requ ired to maintain PT at 2 +/- 0.2 INR decreased from a baseline value of 4.2 to between 3.4 and 4.0 during the 6 weeks of suramin plus warfarin treatme nt. Despite failing to demonstrate equivalence applying a 90% confidence in terval approach, required reductions in warfarin dose were clinically minor and the combination was well tolerated. Based on these results, the eligib ility criteria for a large ongoing randomized study were amended to allow e ntry of men receiving warfarin therapy. This interaction study, together wi th experience gained in a larger trial setting, has confirmed that warfarin and suramin can be safely coadministered, provided that coagulation status is appropriately monitored.