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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).

Division of Clinical Oncology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, 734-8551, Japan.
Gastric Cancer (Impact Factor: 3.99). 02/2011; 14(1):72-80. DOI: 10.1007/s10120-011-0009-5
Source: PubMed

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

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