Journal of Tumour Research & Reports

Abstract

A Cholesterol Derivative (Hydroxysterol; 24-Ethyl-Cholestane-3β,5α,6α-Triol) With High Antitumor Activity Against a Variety of Sarcomas

Nabil Habib, Hajj G, Daaboul H, Jabbour A, Zeitouni H, Khalifeh R and Kassem N

Oxygenated derivatives of cholesterol, Oxysterol, have different physicochemical properties acting on cell membranes. Agents belonging to this class of compounds have been found to induce apoptosis and to harbour antitumor activity demonstrated in vitro and in vivo. 24-ethyl-cholestane- 3β, 5α, and 6α-triol is a new hydroxysterol developed in our lab. Unlike other derivatives, it is, to our knowledge, the first one tested in the clinic. We have treated eight patients suffering from different types of sarcomas with bad performance status. Three patients were suffering from carcinosarcomas, one from angiosarcoma, one from osteosarcoma, one from low-grade chondrosarcoma, one from poorly differentiated sarcoma and one from Ewing sarcoma. All of them were pre-treated with chemotherapy with or without radiotherapy. Seven patients were females and one male with ages ranging from 21 to 82 (median age 55 y). None of these 8 patients experienced any side-effect despite the fact that one of them was taking a mild chemotherapy in association with hydroxysterol. This patient was excluded from the evaluation of the response to therapy. Among the 7 patients evaluable for response, we observed 4 complete responses (one of them confirmed by PET scan), two stable diseases and one progressive disease. The complete responses were observed in one osteosarcoma, one Ewing sarcoma, one angiosarcoma and one carcinosarcoma. As with our previous experience with this drug, no clinical or biological side-effect was observed and symptom control was achieved rapidly in all 6 symptomatic patients. We believe that this new compound deserves to be tested in phase II trials in patients suffering from sarcomas.