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- Title
Correlation of UGT1A1 Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101).
- Authors
Harada, Kazuaki; Yamamura, Takahiro; Muto, Osamu; Nakamura, Michio; Sogabe, Susumu; Sawada, Kentaro; Nakano, Shintaro; Yagisawa, Masataka; Muranaka, Tetsuhito; Dazai, Masayoshi; Tateyama, Miki; Kobayashi, Yoshimitsu; Kato, Sosuke; Hatanaka, Kazuteru; Kawamoto, Yasuyuki; Yuki, Satoshi; Sakata, Yuh; Sakamoto, Naoya; Komatsu, Yoshito
- Abstract
The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.
- Subjects
PANCREATIC duct; IRINOTECAN; GENETIC polymorphisms; TREATMENT effectiveness; COHORT analysis; PANCREATIC intraepithelial neoplasia; FEBRILE neutropenia
- Publication
Journal of Clinical Medicine, 2023, Vol 12, Issue 4, p1596
- ISSN
2077-0383
- Publication type
Article
- DOI
10.3390/jcm12041596