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

Am J Clin Oncol. 2001 Apr;24(2):167-71. doi: 10.1097/00000421-200104000-00014.

Abstract

Potential interaction between suramin and warfarin was evaluated when coadministered to patients with cancer. Thirteen men with advanced hormone-refractory prostate cancer were initially stabilized with warfarin to a prothrombin time (PT) of 2 +/- 0.2 International Normalized Ratio (INR) during a lead-in period of 4 weeks. A baseline daily warfarin dose was established, and treatment with suramin plus hydrocortisone was then started. The effect of suramin on the anticoagulant activity of warfarin was assessed in each patient by comparing his baseline warfarin dose with average daily doses required to maintain the same INR level over each of the initial 6 weeks of a 12-week course of suramin treatment. The average daily dose of warfarin required 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 treatment. Despite failing to demonstrate equivalence applying a 90% confidence interval approach, required reductions in warfarin dose were clinically minor and the combination was well tolerated. Based on these results, the eligibility criteria for a large ongoing randomized study were amended to allow entry of men receiving warfarin therapy. This interaction study, together with experience gained in a larger trial setting, has confirmed that warfarin and suramin can be safely coadministered, provided that coagulation status is appropriately monitored.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Blood Coagulation / drug effects*
  • Drug Interactions
  • Humans
  • Hydrocortisone / pharmacology
  • Hydrocortisone / therapeutic use
  • International Normalized Ratio
  • Male
  • Prostatic Neoplasms / drug therapy
  • Prothrombin Time
  • Suramin / pharmacology*
  • Suramin / therapeutic use
  • Warfarin / pharmacology*
  • Warfarin / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Anticoagulants
  • Antineoplastic Agents
  • Warfarin
  • Suramin
  • Hydrocortisone