UGT1A1*28 and *6 polymorphisms and nilotinib-induced unconjugated hyperbilirubinemia in a Japanese patient with chronic myelogenous leukemia

详细信息    查看全文

• 作者：Kohichi Takada (1)
  Tsutomu Sato (1)
  Satoshi Iyama (1)
  Kaoru Ono (1)
  Yusuke Kamihara (1)
  Kazuyuki Murase (1)
  Yutaka Kawano (1)
  Tsuyoshi Hayashi (1)
  Koji Miyanishi (1)
  Yasushi Sato (1)
  Masayoshi Kobune (1)
  Rishu Takimoto (1)
  Junji Kato (1)
  
• 关键词：Nilotinib ; Hyperbilirubinemia ; UGT1A1 ; Polymorphism
• 刊名：International Cancer Conference Journal
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：1
• 期：4
• 页码：220-223
• 全文大小：215KB
• 参考文献：1. Saglio G, Kim DW, Issaragrisil S et al (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New Engl J Med 362:2251鈥?259 CrossRef
  2. Kantarjian H, Shah NP, Hochhaus A et al (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. New Engl J Med 362:2260鈥?270 CrossRef
  3. Rosti G, Palandri F, Castagnetti F et al (2009) Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood 114:4933鈥?938 CrossRef
  4. Cortes JE, Jones D, O鈥橞rien S et al (2010) Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol 28:392鈥?97 CrossRef
  5. Singer JB, Shou Y, Giles F et al (2007) UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia 21:2311鈥?315 CrossRef
  6. Monaghan G, Ryan M, Seddon R et al (1996) Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert鈥檚 syndrome. Lancet 347:578鈥?81 CrossRef
  7. Ando Y, Chida M, Nakayama K et al (1998) The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics 8:357鈥?60 CrossRef
  8. Kaniwa N, Kurose K, Jinno H et al (2005) Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C聽>聽T (P229L) found in an African-American. Drug Metab Dispos 33:458鈥?65 CrossRef
  9. Saeki M, Saito Y, Jinno H et al (2006) Haplotype structures of the UGT1A gene complex in a Japanese population. Pharmacogenomics J 6:63鈥?5 CrossRef
  10. Onoue M, Terada T, Kobayashi M et al (2009) UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. Int J Clin Oncol 14:136鈥?42 CrossRef
  11. Hahn KK, Wolff JJ, Kolesar JM (2006) Pharmacogenetics and irinotecan therapy. Am J Health Syst Pharm 63:2211鈥?217 CrossRef
  12. Innocenti F, Undevia SD, Iyer L et al (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382鈥?388 CrossRef
  13. Ando Y, Saka H, Ando M et al (2000) Polymorphisms of UDP glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res 60:6921鈥?926
  14. Ramchandani RP, Wang Y, Booth BP et al (2007) The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity. J Clin Pharmacol 47:78鈥?6 CrossRef
  15. Minami H, Sai K, Saeki M et al (2007) Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genomics 17:497鈥?04 CrossRef
  16. Araki K, Fujita K, Ando Y et al (2006) Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer. Cancer Sci 97:1255鈥?259 CrossRef
  17. Kim MK, Cho HS, Bae YK et al (2009) Nilotinib-induced hyperbilirubinemia: is it a negligible adverse event? Leuk Res 33:e159鈥揺161 CrossRef
  18. Fujita K, Sugiyama M, Akiyama Y et al (2011) The small-molecule tyrosine kinase inhibitor nilotinib is a potent noncompetitive inhibitor of the SN-38 glucuronidation by human UGT1A1. Cancer Chemother Pharmacol 67:237鈥?41 CrossRef
  19. Rosti G, Castagnetti F, Gugliotta G et al (2011) Physician鈥檚 guide to the clinical management of adverse events on nilotinib therapy for the treatment of CML. Cancer Treat Rev 38:241鈥?48 CrossRef
  20. National Comprehensive Cancer Network (2012) NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed 8 Apr 2012
  
• 作者单位：Kohichi Takada (1)
  Tsutomu Sato (1)
  Satoshi Iyama (1)
  Kaoru Ono (1)
  Yusuke Kamihara (1)
  Kazuyuki Murase (1)
  Yutaka Kawano (1)
  Tsuyoshi Hayashi (1)
  Koji Miyanishi (1)
  Yasushi Sato (1)
  Masayoshi Kobune (1)
  Rishu Takimoto (1)
  Junji Kato (1)
  
  1. Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
  

文摘

Nilotinib, a second-generation tyrosine kinase inhibitor of BCR-ABL, has shown superior efficacy compared with imatinib for the treatment of chronic myelogenous leukemia (CML). Unconjugated hyperbilirubinemia has been the most frequent adverse event with laboratory abnormality observed in clinical trials of nilotinib. The homozygosity for uridine diphosphate glucuronosyltransferase (UGT) 1A1*28 polymorphism has been reported to increase the risk of nilotinib-induced unconjugated hyperbilirubinemia in Caucasians. However, the frequency of UGT1A1*28 is low in Asians, including Japanese. On the other hand, the UGT1A1*6 allele mutation, which is extremely rare in Caucasians, is more frequent than the UGT1A1*28 allele in the Japanese population. Herein, we present a patient with CML who developed grade 3 unconjugated hyperbilirubinemia after being treated with nilotinib. We found that the patient was heterozygous for both UGT1A1*28 and *6. Our findings suggest that the compound heterozygosity for UGT1A1*28 and *6 could be a cause of unconjugated hyperbilirubinemia during nilotinib treatment.