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International Journal of Clinical Oncology

Erschienen in:

01.04.2014 | Original Article

Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia

verfasst von: Takashi Shibata, Yosuke Minami, Ayako Mitsuma, Sachi Morita, Megumi Inada-Inoue, Tomoyo Oguri, Tomoya Shimokata, Mihoko Sugishita, Tomoki Naoe, Yuichi Ando

Erschienen in: International Journal of Clinical Oncology | Ausgabe 2/2014

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Abstract

Background

Nilotinib is a BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism UGT1A1*28 (*28)/*28 has been linked to an increased risk of hyperbilirubinemia in patients with CML who receive nilotinib. Beside *28, UGT1A1*6 (*6) is another important variant allele in Japanese patients because it is associated with adverse events of irinotecan, metabolized by UGT1A1. We retrospectively investigated the association between severe toxicity of nilotinib and UGT1A1 polymorphisms (*6 and*28) in Japanese patients with CML.

Patients and methods

Eight patients with cytogenetically confirmed CML who were receiving nilotinib were studied to explore the association of UGT1A1 polymorphisms with severe nilotinib-related toxicity. Genotyping analyses were determined for *6 and *28.

Results

All 3 patients with the *6/*6 or *6/*28 genotype had severe toxicity, including QT interval prolongation (grade 3), elevated lipase levels (grade 3) plus hyperbilirubinemia (grade 2), and anemia (grade 3) plus hepatic cyst hemorrhage (grade 2) in 1 patient each. Among the 5 patients with the *6/*1 or *1/*1 genotype, 1 had elevated lipase levels (grade 3) and another had severe pain in the lower extremities (grade 3).

Conclusion

These findings suggest that UGT1A1 polymorphisms are important determinants of severe toxicity of nilotinib in Japanese patients.

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Titel: Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia
verfasst von: Takashi Shibata
Yosuke Minami
Ayako Mitsuma
Sachi Morita
Megumi Inada-Inoue
Tomoyo Oguri
Tomoya Shimokata
Mihoko Sugishita
Tomoki Naoe
Yuichi Ando
Publikationsdatum: 01.04.2014
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 2/2014
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-013-0562-5

Springer Medizin

Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia