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.
ABSTRACT 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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ABSTRACT: Gastric cancer is known to have a high incidence in several countries around the world, while the treatment of advanced gastric cancer remains a challenge. Recent studies have shown that the antibody bevacizumab, a monoclonal vascular endothelial growth factor antibody, is effective in several solid tumors, while experience regarding its effect on gastric cancer remains limited. An 84-year-old patient with advanced gastric remnant cancer with liver and retroperitoneal lymph node metastasis treated in our hospital benefitted from the use of bevacizumab. Since previous treatment with multiple chemotherapeutic agents resulted in progressive disease (PD), a combined treatment with bevacizumab (intravenously) and low-dose S-1 (orally) was administered. With this individualized treatment, the patient exhibited stable disease (SD) and therapy was maintained for a long period of time as maintenance therapy, with a progression-free survival of ∼25 months prior to PD. The serum tumor marker cancer antigen (CA) 199 decreased from 508.7 to 188.1 ng/ml. No severe side-effects of bevacizumab were observed, with the exception of controlled grade I bleeding gums due to the long-term use of bevacizumab. Although no large-scale clinical trials have been conducted to evaluate the role of bevacizumab in maintenance therapy and second- or even third-line treatment of advanced gastric cancer, we showed that bevacizumab combined with S-1 was effective and well-tolerated by this patient, suggesting that it be considered a viable option for elderly patients with advanced gastric cancer as maintenance therapy and that it provide a novel treatment for advanced gastric cancer. However, additional clinical trials are required to evaluate the exact effects of long-term bevacizumab treatment on patients with advanced gastric cancer.01/2013; 1(2):239-242. DOI:10.3892/br.2012.37
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ABSTRACT: Recent clinical trials, such as JCOG9912 and SPIRITS, excluded geriatric patients aged ≥75 years. The clinical significance of intensive chemotherapy for geriatric patients with advanced or recurrent gastric cancer remains unclear. Between 2002 and 2010, 54 consecutive advanced or recurrent gastric cancer patients aged ≥75 years were enrolled in this study. We analyzed the predictors of chemotherapy administration and evaluated the survival benefit of chemotherapy for geriatric patients with advanced or recurrent gastric cancer. A total of 23 geriatric patients received no chemotherapy (GP), whereas the remaining 31 patients were administered chemotherapy (GPC). Of the 54 patients, 20 had severe concomitant illnesses, such as cardiorespiratory disease. Lymph node involvement (P=0.044) and the absence of cardiorespiratory disease (P<0.001) were found to be independently associated with chemotherapy administration. The GPC group exhibited a significantly better prognosis compared to the GP group (median survival time, 19.4 vs. 13.6 months, respectively; P=0.043). GPC patients without cardiorespiratory disease tended to have a better prognosis compared to GP patients without cardiorespiratory disease (P=0.106), whereas there were no significant differences between GP and GPC patients with cardiorespiratory disease. However, administration of chemotherapy was identified as an independent prognostic factor by the Cox proportional hazards model (hazard ratio = 2.609; 95% confidence interval: 1.173-5.761; P=0.019). Therefore, chemotherapy appears to provide a survival benefit in geriatric patients with advanced or recurrent gastric cancer, particularly those without concomitant cardiorespiratory disease.Molecular and Clinical Oncology 01/2015; 3(1):83-88. DOI:10.3892/mco.2014.451
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ABSTRACT: We retrospectively examined the efficacy and safety of S-1 alone or S-1 plus cisplatin (SP) for elderly patients with advanced gastric cancer because the benefit of adding cisplatin in these patients still remains unclear. Among 175 patients aged 70 years or older who received S-1 alone or SP as a first-line therapy between April 2000 and November 2010 at our institution, 104 patients who met eligibility criteria were examined. We investigated safety and efficacy of S-1 and SP. Among these 104 patients, 73 patients received S-1 and 31 patients received SP. The median age was 75 years in the S-1 group and 74 years in the SP group. The response rate was 26.3 % in the S-1 group and 44.0 % in the SP group. Major grade 3 or higher adverse events were observed as follows (S-1 vs. SP): nausea (1.4 vs. 16.1 %), anorexia (16.4 vs. 41.9 %), neutropenia (4.1 vs. 35.5 %), and febrile neutropenia (0 vs. 9.7 %). The median overall survival (OS) was 10.4 months in the S-1 group and 17.8 months in the SP group. Treatment of SP and histology of intestinal type were detected as independent, good prognostic factors in multivariate analysis. SP might improve OS with some added toxicity compared to S-1 alone in elderly patients with advanced gastric cancer.Journal of Cancer Research and Clinical Oncology 10/2013; 139(12). DOI:10.1007/s00432-013-1537-7 · 3.01 Impact Factor