First-Line FOLFIRI Improves Time to Treatment Failure and Is Better Tolerated vs ECX in Advanced Gastric Cancer


Key Points

  • FOLFIRI improved time to treatment failure vs ECX; no differences in progression-free or overall survival were observed.
  • FOLFIRI was better tolerated than ECX.

In a phase III French Intergroup trial reported in the Journal of Clinical Oncology, Guimbaud et al found that FOLFIRI (fluorouracil [5-FU], leucovorin, and irinotecan) significantly prolonged time to treatment failure compared with ECX (epirubicin, cisplatin, and capecitabine) in first-line treatment of advanced gastric or esophagogastric junction adenocarcinoma. FOLFIRI was better tolerated than ECX.

Study Details

In this open-label trial carried out in 71 centers, 416 patients with locally advanced or metastatic gastric or esophagogastric junction cancer were randomly assigned between June 2005 and May 2008 to receive ECX (n = 209; epirubicin at 50 mg/m2 plus cisplatin at 60 mg/m2 on day 1 followed by oral capecitabine at 1 g/m2 twice per day from day 2 to day 15 every 3 weeks) or FOLFIRI (n = 207; irinotecan at 180 mg/m2 and leucovorin at 400 mg/m2 followed by 5-FU as a 400 mg/m2 bolus and 5-FU at 2,400 mg/m2 as a 46-hour continuous infusion every 2 weeks).

Second-line treatment was predefined as FOLFIRI for the ECX group and ECX for the FOLFIRI group. The primary endpoint was time to treatment failure for first-line therapy.

Overall, patients had a median age of 61 years, 74% were male, 82% had WHO performance status of 0 or 1, and 65% had gastric tumors.

Better Time to Treatment Failure

After a median follow-up of 31 months, median time to treatment failure was 5.1 months with FOLFIRI vs 4.2 months with ECX (hazard ratio [HR] = 0.77, P = .008). Median progression-free survival was 5.75 months vs 5.29 months (HR = 0.99, P = .96). Response rates were 38% vs 39%, with complete response in 4% vs 4%.

Second-line therapy was received by 39% of patients in the FOLFIRI group and 48% of patients in the ECX group (P = .06). Median overall survival was 9.72 months vs 9.49 months (HR = 1.01, P = .95).


Grade 3 or 4 toxicity occurred in 69% of the FOLFIRI group vs 84% of the ECX group (P < .001), including hematologic adverse events in 38% vs 64.5% (P < .001) and nonhematologic adverse events in 53% vs 53.5% (P = .81). Treatment was discontinued due to adverse events in 3.9% vs 14.5%.

The investigators concluded: “FOLFIRI as first-line treatment for advanced gastric and [esophagogastric junction] cancer demonstrated significantly better [time to treatment failure] than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.”

Rosine Guimbaud, PhD, of Centre Hospitalier Universitaire Toulouse, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Laboratoire Roche and Laboratoire Pfizer, Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.