Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study.

Department of Gastroenterology and Gastrointestinal Oncology, Kitasato University School of Medicine, Kitasato University East Hospital, 2-1-1 Asamizodai, Sagamihara, Kanagawa, 228-8520, Japan.
Cancer Chemotherapy and Pharmacology (Impact Factor: 2.77). 09/2009; 65(6):1093-9. DOI: 10.1007/s00280-009-1114-6
Source: PubMed


This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.
Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.
Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.
The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

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    • "TS-1 is widely used as first-line treatment for advanced gastric cancer in Asian countries. Phase II studies of TS-1 have noted responses of 44–54% in patients with advanced gastric cancer, but TS-1 has lower responses of 13–33% in this type of cancer when combined with poor clinical condition, including advanced age and poor PS (12,22,23). Weekly paclitaxel and irinotecan regimens are usually used as second-line treatment for advanced gastric cancer with a response rate of 14–21% (24,25). "
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    ABSTRACT: Combination chemotherapy is a standard treatment approach in advanced gastric cancer. However, combination chemotherapy for advanced gastric cancer is often associated with severe treatment-related toxicities and most oncologists are reluctant to perform combination chemotherapy in patients with a poor clinical condition. We retrospectively investigated the efficacy and tolerability of single-agent chemotherapy in patients with recurrent or metastatic gastric cancer with poor performance status (PS). We reviewed advanced gastric adenocarcinoma patients who received first-line single-agent palliative chemotherapy due to poor PS between June 2006 and December 2010. A total of 125 patients with Eastern Cooperative Oncology Group (ECOG) PS 2-3, whose general condition did not allow combination chemotherapy, were enrolled. Four single agents were used: TS-1 (n=63), paclitaxel (n=42), irinotecan (n=15) and capecitabine (n=5). The median age was 66 years, with a range of 25-81 years. The percent response rate and rate of stable disease (SD) were 19.2 and 35.2%, respectively, giving a disease control rate of 54.4%. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.73-5.06). The median overall survival (OS) was 9.1 months (95% CI, 7.70-10.56) with a 1-year survival rate of 31.2%. Multivariate analysis demonstrated that the independent prognostic factors for OS were chemotherapy regimen (capecitabine) [reference: TS-1, hazard ratio (HR), 5.00; 95% CI, 1.81-13.81; P=0.002], no second-line chemotherapy (HR, 2.3; 95% CI, 1.48-3.57; P=0.001), bone metastasis (HR, 2.73; 95% CI, 1.22-6.09; P=0.014), ECOG PS 3 (HR, 38.10; 95% CI, 13.72-105.78; P=0.001), Glasgow prognostic score (GPS) ≥1 (HR, 1.88; 95% CI, 1.24-2.85; P=0.003) and chemotherapy response [SD + progressive disease (PD) + not evaluable (NE); HR, 2.37; 95% CI, 1.39-4.05; P=0.002)]. First-line single-agent palliative chemotherapy demonstrated a relatively good clinical efficacy for recurrent or metastatic gastric cancer patients with poor PS.
    Experimental and therapeutic medicine 10/2012; 4(4):562-568. DOI:10.3892/etm.2012.644 · 1.27 Impact Factor
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    • "S-1 is an oral fluoropyrimidine prodrug that has confirmed efficacy against various solid tumors, both alone and in combination with other cytotoxic drugs [1] [12] [14] [19] [29]. S-1 monotherapy has yielded good results against advanced biliary tract cancer [5] [24], and gemcitabine/S-1 combination therapy has yielded promising results with acceptable toxicity levels for patients with advanced pancreatic cancer [15] [16] [28]. "
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    ABSTRACT: We aimed to evaluate the efficacy and safety of gemcitabine/S-1 combination chemotherapy for the treatment of patients with advanced biliary tract cancer. Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The primary endpoint was overall survival. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 was administered daily at a dose of 60 mg/m(2) on days 1-14. This schedule was repeated every 3 weeks until disease progression or patient refusal. Twenty-five patients were enrolled between October 2007 and January 2009. Eleven patients (44%) had extrahepatic bile duct cancer, 5 (20%) had intrahepatic bile duct cancer, 8 had gallbladder cancer (32%), and 1 (4%) had ampulla of Vater cancer. The median overall survival time was 12.7 months (95% CI, 8.4-23.5 months), and the 1-year survival rate was 52.0% (95% CI, 31.2-69.2%). Of the 23 patients with evaluable target regions, seven patients experienced a partial response, and an overall response rate was 30.4%. The following grade 3-4 hematological toxicities occurred: neutropenia (56%), leukopenia (24%), anemia (8%) and thrombocytopenia (4%). In spite of the high incidence of grade 3-4 neutropenia, no patients developed febrile neutropenia in the present study. The major grade 3-4 non-hematological toxicities were fatigue (8%), anorexia (8%) and diarrhea (4%). Gemcitabine/S-1 combination chemotherapy offered a promising survival benefit with acceptable toxicity in patients with advanced biliary tract cancer.
    Cancer Chemotherapy and Pharmacology 06/2011; 67(6):1429-34. DOI:10.1007/s00280-010-1443-5 · 2.77 Impact Factor
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    ABSTRACT: Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC. We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups. The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively. Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.
    Gastric Cancer 11/2010; 13(4):245-50. DOI:10.1007/s10120-010-0566-z · 3.72 Impact Factor
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