Meyer M, Jeong E, Bolinger B, Chen L, Lenehan P, Slichenmyer W, Natale R B
Pfizer Global Research and Development, Ann Arbor Laboratories, Michigan 48105, USA.
Am J Clin Oncol. 2001 Apr;24(2):167-71. doi: 10.1097/00000421-200104000-00014.
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.
在癌症患者中联合使用苏拉明和华法林时，对它们之间潜在的相互作用进行了评估。13名患有晚期激素难治性前列腺癌的男性患者，在为期4周的导入期内，先用华法林将凝血酶原时间（PT）稳定在国际标准化比值（INR）为2±0.2。确定了华法林的基线日剂量，然后开始用苏拉明加氢化可的松进行治疗。通过比较每位患者的基线华法林剂量与在苏拉明治疗的12周疗程的最初6周内维持相同INR水平所需的平均日剂量，评估苏拉明对华法林抗凝活性的影响。在苏拉明加华法林治疗的6周内，将PT维持在2±0.2 INR所需的华法林平均日剂量从基线值4.2降至3.4至4.0之间。尽管采用90%置信区间法未能证明等效性，但华法林剂量所需的降低在临床上较小，且该联合用药耐受性良好。基于这些结果，一项正在进行的大型随机研究的入选标准进行了修订，以允许接受华法林治疗的男性患者入组。这项相互作用研究，以及在更大规模试验中获得的经验，证实了只要适当监测凝血状态，华法林和苏拉明可以安全地联合使用。
