Yutaka Negoro1, Ryoichi Yano2, Mari Yoshimura2, Yoko Suehiro2, Shinji Yamashita2, Takaaki Kodawara2, Kyohei Watanabe2,3, Hitoshi Tsukamoto2, Toshiaki Nakamura4, Maiko Kadowaki5, Miwa Morikawa5, Yukihiro Umeda5, Masaki Anzai5, Tamotsu Ishizuka5, Nobuyuki Goto2. 1. Department of Pharmacy, University of Fukui Hospital, 23-3 Matsuoka-shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan. ynegoro@u-fukui.ac.jp. 2. Department of Pharmacy, University of Fukui Hospital, 23-3 Matsuoka-shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan. 3. Medical Research Support Center, University of Fukui Hospital, Yoshida-gun, Fukui, Japan. 4. Education and Research Center for Clinical Pharmacy, Osaka Pharmaceutical University, Takatsuki, Osaka, Japan. 5. Third Department of Internal Medicine, University of Fukui Hospital, Yoshida-gun, Fukui, Japan.
Abstract
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.
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.
Authors: Y Ando; H Saka; M Ando; T Sawa; K Muro; H Ueoka; A Yokoyama; S Saitoh; K Shimokata; Y Hasegawa Journal: Cancer Res Date: 2000-12-15 Impact factor: 12.701