Hata Tsuyoshi, Kudo Toshihiro, Sakai Daisuke, Takahashi Hidekazu, Haraguchi Naotsugu, Nishimura Junichi, Hata Taishi, Mizushima Tsunekazu, Yamamoto Hirofumi, Doki Yuichiro, Mori Masaki, Satoh Taroh
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Cancer Chemother Pharmacol. 2016 Aug;78(2):389-96. doi: 10.1007/s00280-016-3080-0. Epub 2016 Jun 23.
Capecitabine and S-1 are orally administered fluoropyrimidine anticancer drugs widely used to treat gastrointestinal cancer. While anticoagulant therapy for cancer patients is recommended, many studies have shown that the effects of warfarin are enhanced by its interaction with fluoropyrimidine. We investigated the effects of capecitabine or S-1 on the anticoagulant activity of warfarin in patients coadministered both drugs.
We retrospectively investigated the clinical features of and anticoagulant activity in nine consecutive patients who received capecitabine or S-1 in combination with warfarin from January 2008 to December 2014 at our institution. The prothrombin time international normalized ratio divided by current warfarin dosage (PT-INR/dose) was measured over time to evaluate warfarin titer in each patient.
Reductions in warfarin dosage were required, from 2.6 mg/day before chemotherapy to a minimum of 1.7 mg/day after chemotherapy initiation, on average. The median time until the first dosage reduction after initiation was 22 days for the capecitabine group and 43 days for the S-1 group. The median time until minimal dosage of warfarin was reached was 43 days in both groups. PT-INR/dose was elevated from 0.85 before chemotherapy to a maximum of 1.41 after its initiation. The median time until the maximal PT-INR/dose was reached was 46 days for the capecitabine group and 46.5 days for the S-1 group.
The anticoagulant activity of warfarin may be enhanced by coadministration with capecitabine or S-1. Close monitoring of anticoagulant activity is required to avoid a hyperfibrinolytic state due to a severe adverse interaction.
卡培他滨和S-1是口服氟嘧啶类抗癌药物，广泛用于治疗胃肠道癌症。虽然推荐对癌症患者进行抗凝治疗，但许多研究表明，华法林与氟嘧啶相互作用会增强其效果。我们研究了卡培他滨或S-1对同时服用这两种药物的患者中，华法林抗凝活性的影响。
我们回顾性研究了2008年1月至2014年12月在我院连续接受卡培他滨或S-1联合华法林治疗的9例患者的临床特征和抗凝活性。随时间测量凝血酶原时间国际标准化比值除以当前华法林剂量（PT-INR/剂量），以评估每位患者的华法林效价。
平均而言，需要降低华法林剂量，从化疗前的2.6毫克/天降至化疗开始后的最低1.7毫克/天。卡培他滨组开始后首次减量的中位时间为22天，S-1组为43天。两组达到华法林最低剂量的中位时间均为43天。PT-INR/剂量从化疗前的0.85升高至开始后的最高1.41。卡培他滨组达到最大PT-INR/剂量的中位时间为46天，S-1组为46.5天。
华法林与卡培他滨或S-1联合使用可能会增强其抗凝活性。需要密切监测抗凝活性，以避免因严重不良相互作用导致的高纤维蛋白溶解状态。
