title: Survival prolongation after treatment failure of first-line chemotherapy in patients with advanced gastric cancer: combined analysis of the Japan Clinical Oncology group trials JCOG9205 and JCOG9912.
abstract: BACKGROUND
  Two randomized phase III trials of first-line chemotherapy for advanced gastric cancer (JCOG9205 and JCOG9912) conducted by the Japan Clinical Oncology Group used 5-fluorouracil continuous infusion (5-FUci) as the control arm. New active agents (e.g., S-1, irinotecan, and taxanes) were introduced as second-line chemotherapy in the late 1990s after JCOG9205. This combined analysis evaluated whether patients in the 5-FUci arm of JCOG9912 exhibited better survival after adjusting for baseline factors and also investigated the cause of survival prolongation.
  
  
  METHODS
  The subjects were patients assigned to the 5-FUci arms who met the eligibility criteria of both JCOG9205 and JCOG9912. Overall survival (OS), time to treatment failure (TTF), and survival after treatment failure in the first-line chemotherapy (OS-TTF) were compared after adjusting baseline characteristics using the Cox proportional hazard model. Second-line chemotherapy details were also reviewed.
  
  
  RESULTS
  The combined analysis included 89 and 230 patients in JCOG9205 and JCOG9912, respectively. After adjusting baseline characteristics, TTF was similar between groups (HR 0.95; 95 % CI, 0.73-1.26). However, both OS (HR, 0.74; 95 % CI, 0.56-0.99) and OS-TTF (HR, 0.76; 95 % CI, 0.57-1.01) were longer in JCOG9912. More patients in JCOG9912 received second-line chemotherapy (83 vs. 52 %) with new drugs (77 vs. 10 %) than in JCOG9205. OS-TTF was substantially prolonged in patients who received second-line chemotherapy (HR, 0.66; 95 % CI, 0.46-0.95).
  
  
  CONCLUSIONS
  OS and OS-TTF were longer in JCOG9912 than JCOG9205. Second-line chemotherapy with new drugs is a potential reason for the observed prolongation of survival.
authors.affiliation: Japan Clinical Oncology Group Data Center, Multi-institutional Clinical Trial Support Center, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, atakashi@ncc.go.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017326:Clinical Trials, Phase III as Topic; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin