Article

Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer

Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
International Journal of Clinical Oncology (Impact Factor: 2.17). 01/2004; 8(6):374-80. DOI: 10.1007/s10147-003-0359-z
Source: PubMed

ABSTRACT Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1 : 0.4 : 1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.
Irinotecan was given intravenously over the course of 90 min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m2 per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100 mg/m2 (level 1; n = 3), to 125 mg/m2 (level 2; n = 3), and 150 mg/m2 (level 3; n = 6).
Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m2 of irinotecan on day 1 and 80 mg/m2 per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.
A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.

0 Followers
 · 
74 Views
  • [Show abstract] [Hide abstract]
    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/m2 PO twice daily on days 1–14 and irinotecan 150 mg/m2 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.
    Asia-Pacific Journal of Clinical Oncology 02/2009; 5(1):46 - 54. DOI:10.1111/j.1743-7563.2009.01191.x · 1.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of colorectal cancer has evolved over the past few years to multidrug therapy including 5-fluouracil (5-FU), irinotecan (CPT-11), and oxaliplatin combination regimens. The addition of novel agents such as bevacizumab and cetuximab has added to the efficacy of chemotherapy in this disease. Identification of molecular determinants of 5-FU, irinotecan, and oxaliplatin efficacy and toxicity is of critical importance for the development of more efficient and less toxic treatment strategies for patients with colon cancer. Markers have been identified that may predict response, survival and toxicity to 5-FU, CPT-11, and platinum-based chemotherapy in patients with advanced colorectal cancer. This review explores these markers as well as potential new markers that have been identified for irinotecan and targeted therapy.
    Current Colorectal Cancer Reports 09/2005; 1(2):91-102. DOI:10.1007/s11888-005-0005-4
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and methods: Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results: A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions: This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.
    Clinical Medicine Insights: Oncology 02/2013; 7:21-30. DOI:10.4137/CMO.S10769