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Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer
Ist Teil von
International journal of clinical oncology, 2019-03, Vol.24 (3), p.256-261
Ort / Verlag
Singapore: Springer Singapore
Erscheinungsjahr
2019
Link zum Volltext
Quelle
SpringerLink (Online service)
Beschreibungen/Notizen
Background
The association between
UGT1A1
polymorphism and etoposide-induced toxicities is still not clear. The aim of this study was to assess the association between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and severe hematologic toxicities in Japanese patients receiving etoposide plus platinum chemotherapy for small-cell lung cancer.
Methods
This retrospective analysis included patients with small-cell lung cancer who had received their first-line chemotherapy with etoposide plus cisplatin or carboplatin, between October 2008 and April 2018, at the University of Fukui Hospital. The relationship between
UGT1A1
polymorphisms and first-cycle neutropenia as well as thrombocytopenia was evaluated.
Results
A total of 55 patients were enrolled. The incidence of grade 4 neutropenia during the first cycle of etoposide-based chemotherapy was higher in patients with homozygous (hmz) polymorphisms for
UGT1A1
*
28
and *
6
(*
28
/*
28
, *
6
/*
6
, and *
6
/*
28
) than in patients with wild-type (wt) (*
1
/*
1
) and heterozygous (htz) (*
1
/*
28
and *
1
/*
6
) polymorphisms (88% vs 43%
P
= 0.03). The incidence of febrile neutropenia and grade 4 thrombocytopenia, however, was not significantly different. Multivariate analysis suggested that grade 4 neutropenia associated significantly with an hmz
UGT1A1
genotype [odds ratio (OR) 11.3;
P
= 0.04] and administration of granulocyte colony-stimulating factor (G-CSF) before the neutrophil counts dropped to < 500 cells/µL (OR;
P
= 0.01).
Conclusions
UGT1A1
*
28
and
UGT1A1
*
6
mutations might be regarded as predictors for etoposide-induced grade 4 neutropenia.