Peng Rou-Jun, Dong Qiu-Mei, Shi Yan-Xia, Cao Ye, Zhou Zhong-Mei, Yuan Zhong-Yu, Li Su, Li Hai, Jiang Wen-Qi
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Ai Zheng. 2006 Aug;25(8):1039-43.
BACKGROUND & OBJECTIVE: Toxicities and their severities vary among advanced gastric cancer patients when they receive the same regimen containing continuous infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the key rate-limiting enzymes which is closely related to toxicities of 5-FU in chemotherapy. This study was to explore the relationship between activity of DPD and concentration of 5-FU, and their correlation to adverse events among advanced gastric cancer patients treated with the same regimen containing 5-FU continuous infusion.
Patients received the same regimen (intravenous injection of paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was collected from 36 patients with advanced gastric cancer before and after chemotherapy to detect the activity of DPD and concentration of 5-FU by high-performance liquid chromatography (HPLC). Adverse events were assessed every cycle.
Serum activity of DPD revealed a unimodel distribution, which globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD activity values were 2.38 and 2.13, respectively. No total DPD deficiency was found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1 589.2 microg/L, which demonstrated normality distribution after a logarithmic transformation was applied. The DPD activity was inversely correlated with 5-FU concentration (r=-0.376, P=0.024). The patients with low activity of DPD were more frequently suffering from severe diarrhea, mucositis, and myelosuppression. And high level of 5-FU concentration led to the increase of adverse events.
Pre-chemotherapy DPD activity and 5-FU concentration during chemotherapy vary among gastric cancer patients, which may help to prevent severe toxicities during the treatment.
晚期胃癌患者接受含持续输注5-氟尿嘧啶（5-FU）的相同方案治疗时，毒性反应及其严重程度存在差异。二氢嘧啶脱氢酶（DPD）是关键的限速酶，与化疗中5-FU的毒性密切相关。本研究旨在探讨晚期胃癌患者接受含5-FU持续输注的相同方案治疗时，DPD活性与5-FU浓度之间的关系及其与不良事件的相关性。
患者接受相同方案（静脉注射紫杉醇75mg/m²、亚叶酸钙200mg/m²和5-FU 375mg/m²，每两周持续输注5-FU 2.5g/m²，共46小时）。采集36例晚期胃癌患者化疗前后的外周血，采用高效液相色谱法（HPLC）检测DPD活性和5-FU浓度。每个周期评估不良事件。
血清DPD活性呈单峰分布，整体符合高斯分布（范围为1.56 - 6.01）。DPD活性的均值和中位数分别为2.38和2.13。患者中未发现完全性DPD缺乏。5-FU浓度在179.2μg/L至1589.2μg/L之间，经对数转换后呈正态分布。DPD活性与5-FU浓度呈负相关（r = -0.376，P = 0.024）。DPD活性低的患者更常出现严重腹泻、黏膜炎和骨髓抑制。5-FU浓度高会导致不良事件增加。
胃癌患者化疗前的DPD活性和化疗期间的5-FU浓度存在差异，这可能有助于预防治疗期间的严重毒性反应。
