title: Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric cancer: results from a phase 3 randomized trial (AMC0101).
abstract: OBJECTIVE
  To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study.
  
  
  METHODS
  We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m(2)) at 3-6 weeks after surgery and oral doxifluridine (460-600 mg/m(2)/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m(2)) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m(2)). The primary endpoint was 3-year recurrence-free survival (RFS).
  
  
  RESULTS
  A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio [HR] 0.70; 95 % confidence interval [CI] 0.54-0.90; p = 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53-0.95; p = 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications.
  
  
  CONCLUSIONS
  The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea, ykkang@amc.seoul.kr.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Yook
authors.forename: Heung-Moon
authors.initials: HM
authors.lastname: Chang
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.forename: Changhoon
authors.initials: C
authors.lastname: Yoo
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Zang
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Yang
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Young Jack
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hwoon-Yong
authors.initials: HY
authors.lastname: Jung
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung Sik
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
chemical_list: D005467:Floxuridine; D016685:Mitomycin; D002945:Cisplatin; C025034:doxifluridine