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Poster display session

1294 - The impact of UGT1A1 genetic polymorphism on safety in unresectable pancreatic cancer patients receiving FOLFIRINOX therapy: A subset analysis of JASPAC 06 study

Date

09 Sep 2017

Session

Poster display session

Presenters

Hiromichi Shirasu

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

H. Shirasu1, K. Omae1, H. Fujii2, N. Mizuno3, M. Ozaka4, H. Ueno5, S. Kobayashi6, K. Uesugi7, N. Kobayashi8, H. Hayashi9, K. Sudo10, N. Okano11, Y. Horita12, K. Kamei13, Y. Seigo14, H. Takafumi15, T. Henmi16, M. Kobayashi17, A. Todaka18, A. Fukutomi1

Author affiliations

  • 1 Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 2 Department Of Clinical Oncology, Jichi Medical University Hospital, Tochigi/JP
  • 3 Department Of Gastroenterology, Aichi Cancer Center Hospital, Nagoya/JP
  • 4 Department Of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation For Cancer Research, 1358550 - Tokyo/JP
  • 5 Department Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 6 Department Of Gastroenterology, Hepatobiliary And Pancreatic Medical Oncology Division, Kanagawa cancer center, 2418515 - Yokohama/JP
  • 7 Department Of Gastroenterology, National Hospital Organaization Shikoku Cancer Center, 7910280 - Matsuyama/JP
  • 8 Department Of Oncology, Yokohama City University Hospital, 236-004 - Yokohama/JP
  • 9 Department Of Gastroenterology And Hepatology, Hokkaido University, 0608648 - Sapporo/JP
  • 10 Division Of Gastroenterology, Chiba Cancer Center, 2608717 - Chiba/JP
  • 11 Department Of Medical Oncology, Kyorin University Faculty of Medicine, 1818611 - Tokyo/JP
  • 12 Department Of Chemotherapy And Internal Medicine, Toyama Prefectural Central Hospital, 9308550 - Toyama/JP
  • 13 Department Of Surgery, Kindai University Faculty of Medicine, 5898511 - Osakasayama/JP
  • 14 Department Of Medical Oncology, Tochigi Cancer Center, 3200834 - Tochigi/JP
  • 15 Medical Science Department, Daiichi Sankyo Co.,Ltd, 1038426 - Tokyo/JP
  • 16 Post-marketing Surveillance Pharmacovigilance Department, Yakult Honsha Co.,Ltd, 1040061 - Tokyo/JP
  • 17 Clinical Trial Promotion Section, Shizuoka industrial Foundation Pharma Valley Center, 4110934 - Tokyo/JP
  • 18 Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, 4118777 - Sunto-gun/JP
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Abstract 1294

Background

UGT1A1*6 and UGT1A1*28 polymorphisms were reported to be associated with increased irinotecan-induced neutropenia. The aim of this subset analysis is to investigate the association between these polymorphisms and toxicities in patients (pts) treated with FOLFIRINOX in the JASPAC 06 study.

Methods

JASPAC 06 study was a nationwide multicenter observational study of FOLFIRINOX for unresectable and recurrent pancreatic cancer. Pts who were screened for UGT1A1*6 and UGT1A1*28, and treated with either original FOLFIRINOX regimen (Oxaliplatin 85 mg/m2, Irinotecan 180 mg/m2, Levofolinate calcium [l-LV] 200 mg/m2, bolus 5-FU 400 mg/m2, and continuous 5-FU 2,400 mg/m2, every two weeks) or modified regimen (Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2, l-LV 200 mg/m2, and continuous 5-FU 2,400 mg/m2, every two weeks) as first-line chemotherapy, were analyzed in this analysis.

Results

Of 399 eligible pts enrolled in JASPAC 06 study, 203 pts were eligible in this analysis. UGT1A1 was reported as wild (W) type (-/-) in 118 pts and heterozygous (H) type (-/*6, -/*28) in 81 pts. Remaining four pts with homozygote (*6/*6, *28/*28) or compound heterozygote (*6/*28) were excluded because of small population. Among 199 pts, 79 pts were treated with original regimen and 120 pts with modified regimen. In the original FOLFIRINOX group, 54/25 pts were W/H type. The median age was 60.5/60 years and PS0 was 57/52%. Incidences of grade 3/4 leukopenia, neutropenia, febrile neutropenia, diarrhea, anorexia and grade 4 neutropenia in pts with W/H type were 28/44%, 59/68%, 24/40%, 4/20%, 9/24% and 24/40%, respectively. In the modified FOLFIRINOX group, 64/56 pts were W/H type. The median age was 62.5/62 years and PS0 was 70/70%. The same toxicities as above were 22/27%, 44/50%, 5/7%, 16/7%, 14/9% and 16/20%, respectively.

Conclusions

Treated with original FOLFIRINOX regimen, pts with UGT1A1 heterozygous type experienced severe toxicities more frequently than those with wild type. In such cases, careful management of not only hematologic but gastrointestinal toxicities seems to be needed.

Clinical trial identification

Legal entity responsible for the study

Shizuoka Industrial Foundation Pharma Valley Center

Funding

Diichi Sankyo Co. Ltd Yakult Honsha Co. Ltd

Disclosure

H. Fujii: Research funding: Yakult Honsha, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Eizai, Merck, and Kyowa-Hakko Kirin, Co., Ltd. N. Mizuno: Research funding: Zeria Pharmaceutical, Taiho Pharmaceutical Co. Ltd., Merck Serono, AstraZeneca, NanoCarrier, Eisai, and MSD. Honoraria: Yakult Honsha Co., Ltd, Taiho Pharmaceutical Co. Ltd., Novartis, Pfizer, and Kyowa-Hakko Kirin. H. Ueno: Honoraria: Yakult Honsha Co., Ltd Research Funding: Yakult Honsha Co., Ltd. S. Kobayashi: Yakult Honsha (Honoraria). N. Okano: Research Funding: Yakult Honsha Co., Ltd, Daiichi Sankyo Co., Ltd. H. Takafumi: Employee of Daiichi Sankyo Co., Ltd. T. Henmi: Employee of Yakult Honsha Co.,Ltd. A. Todaka: Honoraria:Yakult Honsha Co.,Ltd, Daiichi Sankyo Co., Ltd. A. Fukutomi: Honoraria: Yakult Honsha Co.,Ltd, Daiichi Sankyo Co., Ltd. Advisory Role from Yakult Honsha Co.,Ltd. All other authors have declared no conflicts of interest.

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