Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer
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- 作者：Naminatsu Takahara (1)
Yousuke Nakai (1)
Hiroyuki Isayama (1)
Takashi Sasaki (1)
Yumiko Satoh (2)
Daiya Takai (2)
Tsuyoshi Hamada (1)
Rie Uchino (1)
Suguru Mizuno (1)
Koji Miyabayashi (1)
Dai Mohri (1)
Kazumichi Kawakubo (1)
Hirofumi Kogure (1)
Natsuyo Yamamoto (1)
Naoki Sasahira (1)
Kenji Hirano (1)
Hideaki Ijichi (1)
Minoru Tada (1)
Yutaka Yatomi (2)
Kazuhiko Koike (1) - 关键词：Pancreatic cancer ; Irinotecan ; Gemcitabine ; refractory ; Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1)
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2013
- 出版时间：January 2013
- 年：2013
- 卷：71
- 期：1
- 页码：85-92
- 全文大小：207KB
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Yousuke Nakai (1)
Hiroyuki Isayama (1)
Takashi Sasaki (1)
Yumiko Satoh (2)
Daiya Takai (2)
Tsuyoshi Hamada (1)
Rie Uchino (1)
Suguru Mizuno (1)
Koji Miyabayashi (1)
Dai Mohri (1)
Kazumichi Kawakubo (1)
Hirofumi Kogure (1)
Natsuyo Yamamoto (1)
Naoki Sasahira (1)
Kenji Hirano (1)
Hideaki Ijichi (1)
Minoru Tada (1)
Yutaka Yatomi (2)
Kazuhiko Koike (1)
1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
2. Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan - ISSN：1432-0843
文摘
Purpose The aim of this study was to evaluate the efficacy and safety of irinotecan monotherapy in patients with advanced pancreatic cancer (APC). Methods Patients with APC refractory to gemcitabine and S-1 were included. Irinotecan (100?mg/m2) was administered on days 1, 8, and 15 every 4?weeks until disease progression or unacceptable toxicity was observed. The relationship between uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms and clinical outcomes was evaluated. Results Between January 2007 and December 2011, 231 cycles were delivered in 56?patients. Irinotecan was administered as second-line chemotherapy in 35.7?% of patients and as third-line chemotherapy or later in 64.3?%. A partial response was achieved in two (3.6?%) and stable disease in 23 patients (41.0?%), giving a disease control rate of 44.6?%. The median time to progression (TTP) and overall survival (OS) were 2.9 (95?% confidence interval [CI] 1.8-.5) months and 5.3 (95?% CI 4.5-.8) months, respectively. Median survival from the first-line chemotherapy was 19.5 (95?% CI 15.3-3.8) months. Major grade 3/4 adverse events included neutropenia (28.6?%), anemia (12.5?%), and anorexia (10.7?%). Patients with *6 and/or *28 allele(s) (n?=?15) were associated with grade 3/4 neutropenia and anorexia but showed longer TTP (5.3 vs. 1.8?months; p?=?0.05), and OS (8.0 vs. 4.8?months; p?=?0.09) than those without *6 and/or *28 (n?=?29). Conclusions Salvage chemotherapy with irinotecan was moderately effective and well-tolerated in patients with APC refractory to gemcitabine and S-1. UGT1A1 polymorphisms were associated with toxicity and efficacy.