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

Gastric Cancer. 2014;17(3):522-8. doi: 10.1007/s10120-013-0309-z. Epub 2013 Oct 26.


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.

Patients and 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).

Conclusion: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Clinical Trials, Phase III as Topic
  • Drug Combinations
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Irinotecan
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Randomized Controlled Trials as Topic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Tegafur / administration & dosage
  • Time Factors
  • Treatment Failure
  • Treatment Outcome
  • Young Adult


  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Irinotecan
  • Fluorouracil
  • Camptothecin