Kumiko Umemoto1,2, Hideaki Takahashi1, Chigusa Morizane1, Ikuhiro Yamada3, Satoshi Shimizu4, Kazuhiko Shioji5, Yukio Yoshida6, Masayo Motoya7, Nobumasa Mizuno8, Yasushi Kojima9, Takeshi Terashima10, Kazuhiro Uesugi11, Makoto Ueno12, Junji Furuse13, Tetsuo Akimoto2,14, Masafumi Ikeda15. 1. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan. 3. Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation For Cancer Research, Tokyo, Japan. 4. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 5. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 6. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Gastroenterology and Hepatology, Sapporo Medical University, Sapporo, Japan. 8. Department of Gastroenterology, Aichi Cancer Center Hospital, Aichi, Japan. 9. Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan. 10. Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan. 11. Departments of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 12. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. 13. Faculty of Medicine, Department of Medical Oncology, Kyorin University, Tokyo, Japan. 14. Department of Radiation and Oncology and Particle Therapy, National Cancer Center Hospital East, Kashiwa, Japan. 15. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. masikeda@east.ncc.go.jp.
Abstract
BACKGROUND: UGT1A1 *28 and *6 polymorphism is associated with reduced enzyme activity and severe toxicities of irinotecan, especially in patients with homozygous or heterozygous for UGT1A1*28 or *6 polymorphism for both UGT1A1*28 and *6 (double-variant-type of UGT1A1 polymorphism, UGT1A1-DV). FOLFIRINOX is one of the standard treatments for metastatic pancreatic cancer (PC). The optimal dose of irinotecan as a component of the FOLFIRINOX has not been established yet for patients with UGT1A1-DV. PATIENTS AND METHODS: Advanced PC patients with UGT1A1-DV who had received at least one cycle of FOLFIRINOX from December 2013 to March 2016 were collected retrospectively conducted at multicenter in Japan. We evaluated the patient characteristics, efficacy and safety of FOLFIRINOX and investigate the optimal initial dose of irinotecan in Japanese advanced PC patients with UGT1A1-DV. RESULTS: A total of 31 patients were enrolled. Grade 4 neutropenia was seen more frequently (67%; 4/6) in patients who had received irinotecan at an initial dose of ≥ 150 mg/m2 than in those who had received the drug at an initial dose of ≤ 120 mg/m2 (20%; 5/24). The response rate (RR) and progression-free survival (PFS) in patients given irinotecan of ≤ 120 mg/m2 were 21.4% and 8.1 months, respectively, which were consistent with previous report for patients without UGT1A1-DV. CONCLUSION: Based on our findings, we recommend that in Japanese advanced PC patients with UGT1A1- DV treated with FOLFIRINOX, irinotecan be administered at an initial dose of ≤ 120 mg/m2.
BACKGROUND:UGT1A1 *28 and *6 polymorphism is associated with reduced enzyme activity and severe toxicities of irinotecan, especially in patients with homozygous or heterozygous for UGT1A1*28 or *6 polymorphism for both UGT1A1*28 and *6 (double-variant-type of UGT1A1 polymorphism, UGT1A1-DV). FOLFIRINOX is one of the standard treatments for metastatic pancreatic cancer (PC). The optimal dose of irinotecan as a component of the FOLFIRINOX has not been established yet for patients with UGT1A1-DV. PATIENTS AND METHODS: Advanced PC patients with UGT1A1-DV who had received at least one cycle of FOLFIRINOX from December 2013 to March 2016 were collected retrospectively conducted at multicenter in Japan. We evaluated the patient characteristics, efficacy and safety of FOLFIRINOX and investigate the optimal initial dose of irinotecan in Japanese advanced PC patients with UGT1A1-DV. RESULTS: A total of 31 patients were enrolled. Grade 4 neutropenia was seen more frequently (67%; 4/6) in patients who had received irinotecan at an initial dose of ≥ 150 mg/m2 than in those who had received the drug at an initial dose of ≤ 120 mg/m2 (20%; 5/24). The response rate (RR) and progression-free survival (PFS) in patients given irinotecan of ≤ 120 mg/m2 were 21.4% and 8.1 months, respectively, which were consistent with previous report for patients without UGT1A1-DV. CONCLUSION: Based on our findings, we recommend that in Japanese advanced PC patients with UGT1A1- DV treated with FOLFIRINOX, irinotecan be administered at an initial dose of ≤ 120 mg/m2.
Entities:
Keywords:
Advanced pancreatic cancer; Irinotecan; UGT1A1 *28 or *6 polymorphism
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