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

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)

Hiroyuki Narahara  1 , Hiroyasu Iishi, Hiroshi Imamura, Akira Tsuburaya, Keisho Chin, Haruhiko Imamoto, Taito Esaki, Hiroshi Furukawa, Chikuma Hamada, Yuh Sakata
Affiliations
Clinical Trial

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)

Hiroyuki Narahara et al. Gastric Cancer. 2011 Mar.

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.

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Figures

Fig. 1
Fig. 1
Patient disposition. FAS Full analysis set, IRI-S S-1 plus irinotecan, PPS per-protocol set, TTF time to treatment failure
Fig. 2
Fig. 2
Kaplan–Meier estimates of overall survival (a) and time to treatment failure (b) for 315 evaluable patients treated with S-1 monotherapy or S-1 plus irinotecan (IRI-S). MST Median survival time, TTF time to treatment failure, CI confidence interval
Fig. 3
Fig. 3
Subset analysis of overall survival stratified by baseline patient characteristics. CI Confidence interval, ECOG Eastern Cooperative Oncology Group, RECIST Response Evaluation Criteria in Solid Tumors
See this image and copyright information in PMC

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