Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway
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Published:2016-12-02
Issue:1
Volume:79
Page:69-79
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ISSN:0344-5704
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Container-title:Cancer Chemotherapy and Pharmacology
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language:en
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Short-container-title:Cancer Chemother Pharmacol
Author:
He Ming-ming,Zhang Dong-sheng,Wang Feng,Wang Zi-xian,Yuan Shu-qiang,Wang Zhi-qiang,Luo Hui-yan,Ren Chao,Qiu Miao-zhen,Jin Ying,Wang De-shen,Chen Dong-liang,Zeng Zhao-lei,Li Yu-hong,He Yang-yang,Hao Yuan-tao,Guo Pi,Wang Feng-hua,Zeng Yi-xin,Xu Rui-hua
Abstract
Abstract
Background
The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.
Patients and methods
A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.
Results
The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3–4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3–4 AEs. High AUC0–24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS.
Conclusions
Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC.
ClinicalTrials.gov identifier
NCT02090153
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Cancer Research,Pharmacology,Toxicology,Oncology
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