Hirose Koichi, Kozu Chihiro, Yamashita Koshiro, Maruo Eiji, Kitamura Mizuho, Hasegawa Junichi, Omoda Kei, Murakami Teruo, Maeda Yorinobu
Department of Pharmacy, Osaka Rosai Hospital, Sakai, Osaka 591-8025.
Oncol Lett. 2012 Mar;3(3):694-698. doi: 10.3892/ol.2011.533. Epub 2011 Dec 22.
In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r=0.741, p=0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required.
在基于伊立替康（CPT - 11）的化疗中，常引发中性粒细胞减少和腹泻。在本研究中，检测了血浆中7 - 乙基 - 10 - 羟基喜树碱（SN - 38）葡萄糖醛酸苷（SN - 38G）与SN - 38的浓度比在预测CPT - 11诱导的中性粒细胞减少中的临床意义。共纳入17例患有结直肠癌且尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A1基因野生型的患者，并接受CPT - 11治疗，作为FOLFIRI方案[CPT - 11和氟尿嘧啶（5 - FU）]的一部分。在持续输注CPT - 11 2小时后，精确采集15分钟后的血液。采用改良的高效液相色谱（HPLC）法测定血浆中SN - 38、SN - 38G和CPT - 11的浓度。血浆SN - 38G/SN - 38比值的中位数、最大值和最小值分别为4.25、7.09和1.03，表明在UGT1A1基因野生型患者中UGT活性存在个体差异。血浆SN - 38G/SN - 38比值随化疗次数的增加而降低（r = 0.741，p = 0.000669），提示CPT - 11治疗会抑制UGT活性，而低血浆SN - 38G/SN - 38比值会导致更严重的中性粒细胞减少。然而，在该分析中，观察到血浆SN - 38G/SN - 38比值与中性粒细胞减少诱导之间存在两条明显分开的回归线。总之，在UGT1A1基因野生型患者中，参与SN - 38代谢的UGT活性存在个体差异，且每次CPT - 11治疗都会抑制UGT活性。尽管需要进一步研究，但血浆SN - 38G/SN - 38比值的单点测定可能为预测CPT - 11诱导的中性粒细胞减少及调整最佳剂量提供依据。
