Phase II study of S‐1 and irinotecan combination chemotherapy as a first‐line therapy for patients with advanced gastric cancer. Korean Cancer Study Group Protocol ST05‐02

Abstract

Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m 2 PO twice daily on days 1-14 and irinotecan 150 mg/m 2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1-20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3-63.5%). The median time to progression was 5.7 months (95% C.I. 4.3-7.1) and the median overall survival was 10.4 months (95% C.I. 6.1-14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC.

Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells

“…In addition, many patients have primary refractory disease (Catalano et al 2008). Therefore, development of novel molecularly targeted therapeutics is required to improve the treatment outcome for gastric cancer patients (Weichert et al 2008;Kang et al 2009). …”

A randomized phase 2 study of docetaxel and S‐1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy

“…Recent randomized trials yielded encouraging results for S-1-containing doublets. [5][6][7] Docetaxel showed synergism with S-1 in vitro, and the response rate was 46%-67% in several phase 2 trials. [9][10][11] Based on these findings, we designed a randomized phase 2 study to determine whether S-1 or cisplatin shows greater promise as a combination partner of docetaxel for a subsequent phase 3 study.…”

Salvage chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) in previously treated patients with advanced gastric cancer

“…Uedo et al tried 80 mg/m 2 (40 mg/m 2 /week) and reported ORR of 48%, while Komatsu et al, derived from phase I study by themselves, adopted 125 mg/m 2 (62.5 mg/m 2 /week) to obtain better ORR of 54% [ 20 , 21 ]. A Korean study favored triweekly schedule with 150 mg/m 2 (50 mg/m 2 /week) irinotecan with ORR of 49% [ 22 ]. Despite some various ranges of S-1 dose among the studies, we thought that these findings mainly implied dose–response relationship of irinotecan might exist.…”