Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and plati
- PDF / 1,166,074 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 5 Downloads / 208 Views
ORIGINAL ARTICLE
Impact of single‑heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum‑based combination therapy for gastric cancer: a multicenter retrospective study Shintaro Nakano1 · Satoshi Yuki1 · Yasuyuki Kawamoto1 · Hiroshi Nakatsumi2 · Takayuki Ando3 · Shinya Kajiura3 · Ayumu Yoshikawa4 · Kazuaki Harada4 · Kazuteru Hatanaka5 · Aya Tanimoto6 · Atsushi Ishiguro6 · Takuya Honda7 · Masayoshi Dazai8 · Takahide Sasaki9 · Naoya Sakamoto1 · Yoshito Komatsu2 Received: 16 March 2020 / Accepted: 2 June 2020 © The Author(s) 2020
Abstract Background It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy. Methods We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0). Results A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465–1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752–1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173). Conclusion There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity. Keywords Gastric cancer · Irinotecan · UGT1A1 * Yoshito Komatsu [email protected] 1
Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita14, Nishi5, Kita‑Ku, Sapporo, Hokkaido 060‑8648, Japan
2
Division of Cancer Center, Hokkaido University Hospital, Kita14, Nishi5, Kita‑Ku, Sapporo, Hokkaido 060‑8648, Japan
3
Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama‑shi, Toyama 930‑0194, Japan
4
Department of Medical Oncology, Kushiro Rosai Hospital, 13‑23 Nakazono‑cho, Kushiro, Hokkaido 085‑8533, Japan
5
Department of Gastroenterology, Hakodate Municipal Hospital, 1‑10‑1 Minatomachi, Hakodate, Hokkaido 041‑8680, Japan
6
Department of Medical Oncology, Teine Keijinkai Hospital, 1‑40, Maeda1‑12, Teine‑Ku, Sapporo, Hokkaid
Data Loading...
