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TAS-108: a novel steroidal antiestrogen
1University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. abuzdar@mdanderson.org
Summary
TAS-108, a novel steroidal antiestrogen, shows promise for treating tamoxifen-resistant breast cancer. It exhibits antitumor activity and favorable tolerability in early clinical trials, with ongoing studies planned.
Area of Science:
- Oncology
- Pharmacology
- Endocrinology
Background:
- Tamoxifen-resistant breast cancer remains a clinical challenge.
- Novel antiestrogens with distinct mechanisms are needed.
- Estrogen receptor (ER) targeted therapies are crucial in breast cancer treatment.
Purpose of the Study:
- To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of TAS-108.
- To explore the tissue-selective effects of TAS-108.
- To compare the mechanism of action with existing therapies like tamoxifen and fulvestrant.
Main Methods:
- Preclinical studies in tamoxifen-resistant breast cancer cell lines.
- Phase I clinical trial assessing TAS-108 doses (40-160 mg/d).
- Evaluation of pharmacokinetics, tolerability, and biological activity.
Main Results:
- TAS-108 demonstrated strong estrogen receptor binding and antitumor activity in preclinical models.
- Phase I studies showed TAS-108 was well tolerated with linear pharmacokinetics.
- No endometrial effects were observed; tissue-selective agonist activity noted in bone and cardiovascular systems.
- Evidence of biological antitumor activity, including stable disease in several patients.
Conclusions:
- TAS-108 is a well-tolerated novel steroidal antiestrogen with a distinct mechanism of action.
- It shows potential for treating tamoxifen-resistant breast cancer.
- Further clinical development, including Phase II and III studies, is warranted.