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FOLFIRINOX in advanced pancreatic cancer patients with the double-variant type of UGT1A1 *28 and *6 polymorphism: a multicenter, retrospective study.

Authors :
Umemoto, Kumiko
Takahashi, Hideaki
Morizane, Chigusa
Yamada, Ikuhiro
Shimizu, Satoshi
Shioji, Kazuhiko
Yoshida, Yukio
Motoya, Masayo
Mizuno, Nobumasa
Kojima, Yasushi
Terashima, Takeshi
Uesugi, Kazuhiro
Ueno, Makoto
Furuse, Junji
Akimoto, Tetsuo
Ikeda, Masafumi
Source :
Cancer Chemotherapy & Pharmacology. Mar2021, Vol. 87 Issue 3, p397-404. 8p.
Publication Year :
2021

Abstract

<bold>Background: </bold>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.<bold>Patients and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03445704
Volume :
87
Issue :
3
Database :
Academic Search Index
Journal :
Cancer Chemotherapy & Pharmacology
Publication Type :
Academic Journal
Accession number :
148784079
Full Text :
https://doi.org/10.1007/s00280-020-04206-w