PMID- 27913881
OWN - NLM
STAT- MEDLINE
DCOM- 20170602
LR  - 20181113
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 79
IP  - 1
DP  - 2017 Jan
TI  - Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer 
      and clinical prediction by S-1 pharmacogenetic pathway.
PG  - 69-79
LID - 10.1007/s00280-016-3209-1 [doi]
AB  - 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 AUC(0-24h) 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.
FAU - He, Ming-Ming
AU  - He MM
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Zhang, Dong-Sheng
AU  - Zhang DS
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Wang, Feng
AU  - Wang F
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Wang, Zi-Xian
AU  - Wang ZX
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Yuan, Shu-Qiang
AU  - Yuan SQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Wang, Zhi-Qiang
AU  - Wang ZQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Luo, Hui-Yan
AU  - Luo HY
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Ren, Chao
AU  - Ren C
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Qiu, Miao-Zhen
AU  - Qiu MZ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Jin, Ying
AU  - Jin Y
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Wang, De-Shen
AU  - Wang DS
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Chen, Dong-Liang
AU  - Chen DL
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Zeng, Zhao-Lei
AU  - Zeng ZL
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Li, Yu-Hong
AU  - Li YH
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - He, Yang-Yang
AU  - He YY
AD  - Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union 
      Medical College, Beijing, China.
FAU - Hao, Yuan-Tao
AU  - Hao YT
AD  - Department of Medical Statistics and Epidemiology, School of Public Health, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Guo, Pi
AU  - Guo P
AD  - Department of Medical Statistics and Epidemiology, School of Public Health, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Wang, Feng-Hua
AU  - Wang FH
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
FAU - Zeng, Yi-Xin
AU  - Zeng YX
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China.
AD  - Beijing Hospital, Beijing, China.
FAU - Xu, Rui-Hua
AU  - Xu RH
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road 
      East, Guangzhou, 510060, China. xurh@sysucc.org.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT02090153
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20161202
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Drug Combinations)
RN  - 150863-82-4 (S 1 (combination))
RN  - 1548R74NSZ (Tegafur)
RN  - 5VT6420TIG (Oxonic Acid)
RN  - EC 1.14.14.1 (CYP2A6 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2A6)
RN  - EC 2.4.2.10 (Orotate Phosphoribosyltransferase)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Cytochrome P-450 CYP2A6/genetics
MH  - Disease-Free Survival
MH  - Drug Combinations
MH  - Female
MH  - Fluorouracil/pharmacokinetics
MH  - Humans
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Orotate Phosphoribosyltransferase/blood
MH  - Oxonic Acid/administration & dosage/adverse effects/*metabolism
MH  - Pharmacogenomic Testing
MH  - Stomach Neoplasms/*drug therapy/genetics/mortality
MH  - Tegafur/administration & dosage/adverse effects/*metabolism
PMC - PMC5225176
OTO - NOTNLM
OT  - Advanced gastric cancer
OT  - Leucovorin
OT  - Pharmacogenetic
OT  - S-1
COIS- The authors declare that they have no conflict of interest. Ethical approval This 
      study was approved by the independent Institute Research Ethics Committee at the 
      Sun Yat-sen University Cancer Center and conducted in accordance with the 
      Declaration of Helsinki. All patients signed informed consent before 
      participation.
EDAT- 2016/12/04 06:00
MHDA- 2017/06/03 06:00
PMCR- 2016/12/02
CRDT- 2016/12/04 06:00
PHST- 2016/09/09 00:00 [received]
PHST- 2016/11/24 00:00 [accepted]
PHST- 2016/12/04 06:00 [pubmed]
PHST- 2017/06/03 06:00 [medline]
PHST- 2016/12/04 06:00 [entrez]
PHST- 2016/12/02 00:00 [pmc-release]
AID - 10.1007/s00280-016-3209-1 [pii]
AID - 3209 [pii]
AID - 10.1007/s00280-016-3209-1 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2017 Jan;79(1):69-79. doi: 10.1007/s00280-016-3209-1. 
      Epub 2016 Dec 2.