Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002)

Gastric Cancer. 2011 Mar;14(1):72-80. doi: 10.1007/s10120-011-0009-5. Epub 2011 Feb 23.

Abstract

Background: Irinotecan hydrochloride and S-1, an oral fluoropyrimidine, have shown antitumor activity against advanced gastric cancer as single agents in phase I/II studies. The combination of irinotecan and S-1 (IRI-S) is also active against advanced gastric cancer. This study was conducted to compare the efficacy and safety of IRI-S versus S-1 monotherapy in patients with advanced or recurrent gastric cancer.

Methods: Patients were randomly assigned to oral S-1 (80 mg/m² daily for 28 days every 6 weeks) or oral S-1 (80 mg/m² daily for 21 days every 5 weeks) plus irinotecan (80 mg/m² by intravenous infusion on days 1 and 15 every 5 weeks) (IRI-S). The primary endpoint was overall survival. Secondary endpoints included the time to treatment failure, 1- and 2-year survival rates, response rate, and safety.

Results: The median survival time with IRI-S versus S-1 monotherapy was 12.8 versus 10.5 months (P = 0.233), time to treatment failure was 4.5 versus 3.6 months (P = 0.157), and the 1-year survival rate was 52.0 versus 44.9%, respectively. The response rate was significantly higher for IRI-S than for S-1 monotherapy (41.5 vs. 26.9%, P = 0.035). Neutropenia and diarrhea occurred more frequently with IRI-S, but were manageable. Patients treated with IRI-S received more courses of therapy at a relative dose intensity similar to that of S-1 monotherapy.

Conclusions: Although IRI-S achieved longer median survival than S-1 monotherapy and was well tolerated, it did not show significant superiority in this study.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Disease Progression
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Stomach Neoplasms / drug therapy*
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Irinotecan
  • Camptothecin