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Annals of Oncology Advance Access originally published online on January 15, 2009
Annals of Oncology 2009 20(5):868-873; doi:10.1093/annonc/mdn714
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

Evaluation of the safety and tolerability of oral TAS-108 in postmenopausal patients with metastatic breast cancer

T. Saeki1,3,*, S. Noguchi2, K. Aogi3, H. Inaji4, T. Tabei5 and T. Ikeda6

1 Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, Hidaka
2 Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Suita
3 Department of Breast Oncology, Shikoku Cancer Center, Matsuma
4 Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka
5 Division of Breast Oncology, Saitama Cancer Center, Hidaka
6 Department of Surgery, Teikyo University School of Medicine, Japan, Tokyo

* Correspondence to: Prof. T. Saeki, Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. Tel/Fax: +81-42-984-4670; E-mail: tsaeki{at}saitama-med.ac.jp

Background: The potential of TAS-108 for the treatment of breast cancer has been shown by preclinical studies. We therefore investigated the safe dosage, tolerability, and effectiveness on hormone levels and bone metabolism markers and the pharmacokinetics of TAS-108 administered in postmenopausal Japanese women with metastatic breast cancer.

Patients and methods: The subjects had previously undergone standard endocrine therapeutic modalities. TAS-108 was given repeatedly to five patients each, at three dose levels (40, 80, and 120 mg p.o.) once a day after the first daily meal for a scheduled 8 weeks. Plasma concentrations of TAS-108 and its metabolites were measured at the scheduled time points.

Results: Fifteen patients received TAS-108 treatment. Orally administered TAS-108 was well tolerated at doses up to 120 mg and did not cause notable changes either in hormone levels or bone metabolism markers. Pharmacokinetic results indicated dose-dependent increases in plasma levels of TAS-108 and its metabolites. A steady state was achieved by 2 weeks at all dose levels, suggesting no marked accumulation. Clinical benefits were confirmed in 5 of 15 patients.

Conclusions: Repeated oral administration of TAS-108 at doses up to 120 mg was well tolerated, and the plasma level of this compound increased dose-dependently.

Key words: breast cancer, pharmacokinetics, phase I, postmenopausal, SERM, TAS-108

Received for publication October 1, 2008. Accepted for publication October 20, 2008.


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