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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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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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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Abbreviations

CI:

Confidence interval

CR:

Complete response

CVI:

Continuous venous infusion

DPD:

Dihydropyrimidine dehydrogenase

DIF:

DPD-inhibitory fluoropyrimidine

FT:

Tegafur

5-FU:

5-Fluorouracil

MST:

Median survival time

NC:

No change

ND:

Not detected

OPRT:

Orotate phosphoribosyl transferase

PD:

Progressive disease

PR:

Partial response

QOL:

Quality of life

RR:

Response ratio

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Author information

Authors and Affiliations

  1. Department of Clinical Research & Surgery, National Shikoku Cancer Center Hospital, Horinouchi 13, 790-0007, Matsuyama, Japan

    Toshiaki Saeki & Shigemitsu Takashima

  2. Department of Surgery, Niigata Cancer Center, Japan

    Muneaki Sano

  3. Department of Medical Oncology, Cancer Institute Hospital Japanese Foundation for Cancer Research, Japan

    Noboru Horikoshi

  4. Department of Breast Surgery, Aichi Cancer Center Hospital, Japan

    Shigeto Miura

  5. Department of Surgery, Yokohama Minamikyousai Hospital, Japan

    Satoru Shimizu

  6. Second Department of Surgery, Osaka City University Medical School, Japan

    Ken Morimoto

  7. Department of Surgery, Gunma Cancer Center Hospital, Japan

    Morihiko Kimura

  8. Department of Surgery, National Nagoya Hospital, Japan

    Hideaki Aoyama

  9. Department of Surgery, Hanwa Sumiyoshi General Hospital, Japan

    Jun Ota

  10. Ota Clinic, Japan

    Jun Ota

  11. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, Japan

    Shinzaburo Noguchi

  12. Department of Surgical Oncology, Osaka University Medical School, Japan

    Shinzaburo Noguchi

  13. Japan Society for Cancer Chemotherapy, Japan

    Tetsuo Taguchi

Authors
  1. Toshiaki Saeki
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  2. Shigemitsu Takashima
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  12. Tetsuo Taguchi
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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). https://doi.org/10.1007/BF02968301

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  • DOI: https://doi.org/10.1007/BF02968301

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