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A phase II study of S-1 in patients with metastatic breast cancer — A Japanese trial by the S-1 cooperative study group, breast cancer working group

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S-l is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoro-pyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer.


A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n = 111) were enrolled, and 108 patients were regarded as eligible. S-l was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times.


Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CRplus PR) of 41.7% (95% confidence interval: CI, 32.3–51.5%). The incidences of toxicity (≧ grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group.


S-l was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.

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Confidence interval


Complete response


Continuous venous infusion


Dihydropyrimidine dehydrogenase


DPD-inhibitory fluoropyrimidine






Median survival time


No change


Not detected


Orotate phosphoribosyl transferase


Progressive disease


Partial response


Quality of life


Response ratio


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Correspondence to Toshiaki Saeki.

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Saeki, T., Takashima, S., Sano, M. et al. A phase II study of S-1 in patients with metastatic breast cancer — A Japanese trial by the S-1 cooperative study group, breast cancer working group. Breast Cancer 11, 194–202 (2004).

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