TAMOXIFEN AND TOREMIFENE IN BREAST-CANCER - COMPARISON OF SAFETY AND EFFICACY

Purpose: Tamoxifen is currently the standard hormonal treatment of bre ast cancer, both for metastatic disease and in the adjuvant setting. A new antiestrogen, toremifene, was approved recently for use in managi ng metastatic breast cancer in postmenopausal women, Methods: Toremife ne is structurally similar to tamoxifen, differing only by a single ch lorine atom, and has a similar pharmacologic profile. The major differ ence between the two compounds is in the preclinical activity; chronic , high-dose tamoxifen is hepatocarcinogenic in the rat whereas toremif ene is not, Neither agent is hepatocarcinogenic in mice, hamsters, or humans; therefore, clinical relevance of the rat data may not be signi ficant; Results: In a worldwide phase III trial, the two agents demons trated comparable efficacy and safety against metastatic breast cancer . Both agents have shown a significant hypocholesterolemic effect afte r long-term administration, Conclusion: Due to the paucity of long-ter m clinical data an toremifene,, important unresolved questions remain, which include ib effects on bone mineral density, the frequency oa ca rdiac events, and the risk for endometrial cancer, Tamoxifen has been associated with maintenance of bone mineral density, a reduction in ca rdiac events, and a slightly increased risk of endometrial cancer, Tor emifene is not likely to be used as second-line therapy after tamoxife n failure due to cross-resistance, and its ultimate place in therapy o f advanced breast cancer remains to be determined. (C) 1998 by America n Society of Clinical Oncology.