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


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.
Saeki
T
T
Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, Hidaka, Saitama 350-1298, Japan. tsaeki@saitama-med.ac.jp
Noguchi
S
S
Aogi
K
K
Inaji
H
H
Tabei
T
T
Ikeda
T
T
D000284:Administration, Oral; D000368:Aged; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause; D013997:Time Factors; D016896:Treatment Outcome
D020847:Estrogen Receptor Modulators; C482068:TS 108; D004958:Estradiol