Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene

  • Authors:
    • Koichi Hirose
    • Chihiro Kozu
    • Koshiro Yamashita
    • Eiji Maruo
    • Mizuho Kitamura
    • Junichi Hasegawa
    • Kei Omoda
    • Teruo Murakami
    • Yorinobu Maeda
  • View Affiliations

  • Published online on: December 22, 2011     https://doi.org/10.3892/ol.2011.533
  • Pages: 694-698
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Abstract

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.
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March 2012
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Spandidos Publications style
Hirose K, Kozu C, Yamashita K, Maruo E, Kitamura M, Hasegawa J, Omoda K, Murakami T and Maeda Y: Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncol Lett 3: 694-698, 2012
APA
Hirose, K., Kozu, C., Yamashita, K., Maruo, E., Kitamura, M., Hasegawa, J. ... Maeda, Y. (2012). Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncology Letters, 3, 694-698. https://doi.org/10.3892/ol.2011.533
MLA
Hirose, K., Kozu, C., Yamashita, K., Maruo, E., Kitamura, M., Hasegawa, J., Omoda, K., Murakami, T., Maeda, Y."Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene". Oncology Letters 3.3 (2012): 694-698.
Chicago
Hirose, K., Kozu, C., Yamashita, K., Maruo, E., Kitamura, M., Hasegawa, J., Omoda, K., Murakami, T., Maeda, Y."Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene". Oncology Letters 3, no. 3 (2012): 694-698. https://doi.org/10.3892/ol.2011.533