Sadahiro Sotaro, Suzuki Toshiyuki, Maeda Yuji, Ishikawa Kenji, Tanaka Yoichi, Yasuda Seiei, Kamijo Akemi, Makuuchi Hiroyasu, Murayama Chieko
Department of Surgery, Tokai University School of Medicine, Isehara, Japan.
Chemotherapy. 2007;53(6):442-5. doi: 10.1159/000110016. Epub 2007 Oct 22.
Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for the degradation of 5-fluorouracil. The effect of long-term treatment with oral fluoropyrimidines on DPD activity has not been investigated. This study was conducted to examine changes in DPD activity in peripheral mononuclear cells (PMNC) during long-term treatment with oral uracil and tegafur (UFT) for colorectal cancer.
UFT was administered for 5 consecutive days and not administered the next 2 days for 6 months after surgery. PMNC-DPD activity was measured before and 1, 2, 4 and 6 months after starting UFT administration.
In 70 eligible patients, there were no significant variations of PMNC-DPD activity during postoperative administration of UFT for 6 months. Grade 2 or higher adverse events were observed in significantly more patients with low DPD than with high DPD activity (p = 0.018).
There were no significant variations of PMNC-DPD activity during the postoperative administration of UFT for 6 months. Low PMNC-DPD activity before UFT treatment was considered to be a predicting factor for toxicity.
二氢嘧啶脱氢酶（DPD）是5-氟尿嘧啶降解的限速酶。口服氟嘧啶长期治疗对DPD活性的影响尚未得到研究。本研究旨在探讨口服尿嘧啶替加氟（UFT）长期治疗结直肠癌期间外周血单个核细胞（PMNC）中DPD活性的变化。
术后连续5天给予UFT，随后2天不给予，共持续6个月。在开始给予UFT前及给药后1、2、4和6个月测量PMNC-DPD活性。
在70例符合条件的患者中，术后给予UFT 6个月期间PMNC-DPD活性无显著变化。与DPD活性高的患者相比，DPD活性低的患者发生2级或更高等级不良事件的比例显著更高（p = 0.018）。
术后给予UFT 6个月期间PMNC-DPD活性无显著变化。UFT治疗前PMNC-DPD活性低被认为是毒性的预测因素。
