A new oral dihydroxysterol (24-ethyl-cholestane- 3&bgr;,5α,6α-triol) showing activity in the treatment of advanced and metastatic breast cancer

Background

Hydroxysterols are oxygenated derivatives of cholesterol. They have nuclear receptors and have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, and necrosis. Hydroxysterols have also been shown to have antitumor effects in experimental tumor models. (24-ethyl-cholestane- 3ß,5α,6α-triol) is a new oral hydroxysterol. The introduction of additional hydroxyl groups to the cholesterol skeleton facilitates the flux of hydroxysterols across the blood brain barrier. Most of these derivatives have been shown to be very toxic. Our compound (24-ethyl-cholestane- 3ß,5α,6α-triol) is the first dihydroxysterol to have reached the clinical level. It is also one of the rare ones to be safe and non toxic.

Methods

We have treated with this new compound 21 patients suffering from advanced breast cancer. The median age was 55 years. Eighteen patients had stage IV and three stage III. All had received at least one line of chemotherapy (some received more than 4 lines of therapy) and all except 3 previous radiotherapy. Nine patients had a PS: 1, eight had a PS: 2 and four had a PS: 3. Eighty percent were symptomatic and sixty five percent were taking pain killers. Patients received daily 10 mg/Kg of oral (24-ethyl-cholestane- 3ß,5α,6α-triol) divided in 3 equal doses, until disease progression.

Results

Two patients exhibited a complete remission (CR). Nine patients had a partial response (PR), five patients had a stable disease (NC) and five patients had a disease progression (PD). The median duration of response was 11 months and 6 patients are still under treatment. One patient with lepto-meningeal involvement is still alive and under treatment after 49 months. No toxicity was observed so ever. Eighty percent of symptomatic patients had a remarkable symptom control.

Conclusions

These encouraging results make this new and safe drug a good candidate for further clinical trials either alone or in association with other drugs in advanced breast cancer.

Clinical trial identification

Legal entity responsible for the study

Nabil Habib Institute, Beirut, Lebanon.

Funding

Nabil Habib Institute, Beirut, Lebanon.

Disclosure

All authors have declared no conflicts of interest.