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International Journal of Clinical Oncology

Published in:

01-04-2014 | Original Article

Usefulness of one-point plasma SN-38G/SN-38 concentration ratios as a substitute for UGT1A1 genetic information after irinotecan administration

Authors: Kouichi Hirose, Koushiro Yamashita, Hirofumi Takada, Noriko Kaneda, Kohei Fukami, Eiji Maruo, Mizuho Kitamura, Junichi Hasegawa, Yorinobu Maeda

Published in: International Journal of Clinical Oncology | Issue 2/2014

Abstract

Background

It was recently reported that genetic polymorphisms of UDP glucuronyltransferase-1 polypeptide A1 (UGT1A1), a glucuronidation enzyme, were associated with irinotecan (CPT-11) metabolism. The active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38) was glucuronidated (SN-38G) by UGT1A1. Genetic polymorphisms of UGT1A1 were associated with potentially serious adverse events, including neutropenia. Several studies have suggested that the dose of CPT-11 should be decreased in patients homozygous for UGT1A1*6 or UGT1A1*28, or double heterozygotes (*6/*28). However, the reference dose for patients with these genetic polymorphisms is unclear.

Methods

We investigated the relationship between the SN-38G/SN-38 concentration ratio and the dose of CPT-11 in 70 patients with colorectal cancer who received FOLFIRI-based regimens, by measuring the plasma concentrations of CPT-11, SN-38, and SN-38G.

Results

The SN-38G/SN-38 concentration ratio was lower in patients who were homozygous for UGT1A1*6, heterozygous for UGT1A1*6 or UGT1A1*28, or were double heterozygotes compared with patients with wild-type genes. The relative decreases in the SN-38G/SN-38 concentration ratio in patients homozygous for UGT1A1*6 and in double heterozygotes were greater than in patients heterozygous for UGT1A1*6 or UGT1A1*28. Interestingly, decreases in the SN-38G/SN-38 concentration ratio were associated with decreases in the neutrophil count and the final infusion dose of CPT-11.

Conclusion

Our results suggest that the SN-38G/SN-38 concentration ratio is an important factor for guiding dose adjustments, even in patients with wild-type genes. Therefore, the SN-38G/SN-38 concentration ratio, as an index of the patient’s metabolic capacity, is useful for assessing dose adjustments of CPT-11.

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Title: Usefulness of one-point plasma SN-38G/SN-38 concentration ratios as a substitute for UGT1A1 genetic information after irinotecan administration
Authors: Kouichi Hirose
Koushiro Yamashita
Hirofumi Takada
Noriko Kaneda
Kohei Fukami
Eiji Maruo
Mizuho Kitamura
Junichi Hasegawa
Yorinobu Maeda
Publication date: 01-04-2014
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 2/2014
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-013-0558-1

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Abstract

Background

Methods

Results

Conclusion

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