title: Phase II multicentered study of low-dose everolimus plus cisplatin and weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin as first-line treatment for patients with advanced gastric cancer.
abstract: OBJECTIVE
  This phase II trial investigates the efficacy and safety of low-dose everolimus in combination with cisplatin-fluorouracil chemotherapy in patients with advanced gastric cancer.
  
  
  METHODS
  Eligible patients with chemotherapy-naïve advanced gastric cancer received low-dose everolimus (10 mg p.o. on days 1, 8 and 15) plus cisplatin and a weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL) chemotherapy (cisplatin 35 mg/m(2) intravenous infusion for 24 h on days 1 and 8, 5-fluorouracil 2,000 mg/m(2) and leucovorin 300 mg/m(2) intravenous infusion for 24 h on days 1, 8 and 15) every 28 days. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.0.
  
  
  RESULTS
  Forty patients (19 men; 21 women; median age, 54.1 years; range, 33.7-73.3 years) received a median of 6 (range, 1-30; 95% CI, 4.9-8.0) cycles of study treatment. The ORR was 52.5% (21 confirmed partial response). The median progression-free survival and overall survival were 6.9 (95% CI, 4.9-8.4) and 10.5 (95% CI, 8.6-12.3) months, respectively. Most adverse events were mild.
  
  
  CONCLUSIONS
  Adding low-dose everolimus to cisplatin-HDFL chemotherapy failed to increase the ORR as in a preplanned statistical assumption but may prolong progression-free survival in treatment-naïve advanced gastric cancer patients.
authors.affiliation: National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Shen
authors.forename: Chung-Pin
authors.initials: CP
authors.lastname: Li
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Yen
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lin
authors.forename: Zhong-Zhe
authors.initials: ZZ
authors.lastname: Lin
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D000068338:Everolimus; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D020123:Sirolimus