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Fukuda M, Suetsugu T, Shimada M, et al. Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B). Thorac Cancer. 2016;7(4):467-72doi: 10.1111/1759-7714.12360.
Fukuda, M., Suetsugu, T., Shimada, M., Kitazaki, T., Hashiguchi, K., Kishimoto, J., Harada, T., Seto, T., Ebi, N., Takayama, K., Sugio, K., Semba, H., Nakanishi, Y., & Ichinose, Y. (2016). Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B). Thoracic cancer, 7(4), 467-72. https://doi.org/10.1111/1759-7714.12360
Fukuda, Minoru, et al. "Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B)." Thoracic cancer vol. 7,4 (2016): 467-72. doi: https://doi.org/10.1111/1759-7714.12360
Fukuda M, Suetsugu T, Shimada M, Kitazaki T, Hashiguchi K, Kishimoto J, Harada T, Seto T, Ebi N, Takayama K, Sugio K, Semba H, Nakanishi Y, Ichinose Y. Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B). Thorac Cancer. 2016 Jul;7(4):467-72. doi: 10.1111/1759-7714.12360. Epub 2016 May 11. PMID: 27385990; PMCID: PMC4930967.
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Thorac Cancer. 2016 Jul;7(4):467-72. doi: 10.1111/1759-7714.12360. Epub 2016 May 11.

Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B).

Thoracic cancer

Minoru Fukuda, Takayuki Suetsugu, Midori Shimada, Takeshi Kitazaki, Kohji Hashiguchi, Junji Kishimoto, Taishi Harada, Takashi Seto, Noriyuki Ebi, Koichi Takayama, Kenji Sugio, Hiroshi Semba, Yoichi Nakanishi, Yukito Ichinose

Affiliations

  1. Clinical Oncology Center, Nagasaki University Hospital Nagasaki Japan.
  2. Department of Respiratory Medicine Sendai Medical Association Hospital Kagoshima Japan.
  3. Division of Respiratory Diseases, Department of Internal Medicine Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki Japan.
  4. Department of Research and Development of Next Generation Medicine Kyusyu University Fukuoka Japan.
  5. Graduate School of Medical Sciences, Research Institute for Disease of the Chest Kyusyu University Fukuoka Japan.
  6. Department of Thoracic Oncology National Kyusyu Cancer Center Fukuoka Japan.
  7. Department of Respiratory Oncology Medicine Iizuka Hospital Fukuoka Japan.
  8. Department of Pulmonary Medicine Kyoto Prefectual University of Medicine Kyoto Japan.
  9. Department of Thoracic and Breast Surgery Oita University Faculty of Medicine Oita Japan.
  10. Department of Respiratory Medicine Kumamoto Regional Medical Center Kumamoto Japan.
  11. Clinical Research Institute, National Kyusyu Cancer Center Fukuoka Japan.

PMID: 27385990 PMCID: PMC4930967 DOI: 10.1111/1759-7714.12360

Abstract

BACKGROUND: Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study.

METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible.

RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively).

CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients.

Keywords: Gene polymorphism; UGT1A1; irinotecan; lung cancer; prospective

References

  1. Clin Pharmacol Ther. 2004 Jun;75(6):501-15 - PubMed
  2. Biochem Mol Biol Int. 1998 Sep;46(1):21-6 - PubMed
  3. J Clin Oncol. 2006 May 20;24(15):2237-44 - PubMed
  4. Am J Health Syst Pharm. 2006 Nov 15;63(22):2211-7 - PubMed
  5. J Clin Invest. 1998 Feb 15;101(4):847-54 - PubMed
  6. Ther Drug Monit. 2007 Jun;29(3):265-70 - PubMed
  7. J Clin Oncol. 2003 Jan 15;21(2):291-7 - PubMed
  8. Cancer Res. 1991 Aug 15;51(16):4187-91 - PubMed
  9. N Engl J Med. 2002 Jan 10;346(2):85-91 - PubMed
  10. Mol Pharmacol. 2002 Sep;62(3):608-17 - PubMed
  11. J Clin Oncol. 1992 Jan;10 (1):16-20 - PubMed
  12. Cancer Res. 2000 Dec 15;60(24):6921-6 - PubMed
  13. J Clin Oncol. 1993 May;11(5):909-13 - PubMed
  14. Int J Clin Oncol. 2009 Apr;14 (2):136-42 - PubMed
  15. Pharmacogenet Genomics. 2007 Jul;17 (7):497-504 - PubMed
  16. N Engl J Med. 2005 Feb 3;352(5):476-87 - PubMed
  17. J Clin Oncol. 2004 Apr 15;22(8):1382-8 - PubMed
  18. J Thorac Oncol. 2011 Jan;6(1):121-7 - PubMed
  19. Drug Metab Dispos. 2003 Jan;31(1):108-13 - PubMed
  20. Lancet Oncol. 2009 Nov;10 (11):1063-9 - PubMed
  21. Cancer Res. 1994 Aug 15;54(16):4347-54 - PubMed

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