Toremifene and tamoxifen in advanced breast cancer - a double-blind cross-over trial

Abstract

Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM-treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double-blind, cross-over study. 66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40 mg/day or TOR 240 mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10-41%) and with TAM 42% (95% confidence limits 25-61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of over-looking a response rate of 20% or more is less than 1%. In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer.

Tamoxifen: 28-day oral toxicity study in the rat based on the Enhanced OECD Test Guideline 407 to detect endocrine effects

“…Tamoxifen is a triphenylethylene derivative commonly used in the treatment of breast cancer (Furr and Jordan 1984;Hayes et al 1995;Knapp et al 1994;Nayfield et al 1991;Stenbygaard et al 1993).…”

Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor

“…Toremifene (TOR) is a selective estrogen receptor modulator (SERM). It has been reported that the efficacy of treatment with this agent in cases of postmenopausal breast cancer is similar to that of TAM [3,4]. The usual dose of TOR is 40 mg given orally once a day; however, high-dose TOR (120 mg a day; TOR120) has been approved for use in Japan.…”

“…High-dose TOR was reported to compete with estrogen at the site of the ER, to suppress insulin-like growth factor-I-dependent growth [19], and to have non-ER-dependent anti-tumor effects such as suppression of angiogenesis [20,21]. In addition, the agent is effective in TAM-resistant breast cancer and can be used as a secondary endocrine therapy [3,22].…”

Endometrial mullerian adenosarcoma after toremifene treatment in breast cancer patients: a case report

“…Toremifene has a high affinity for the estrogen receptor in breast cancer, is active against the breast cancer, and has an antitumor activity. Stenbygaard et al 10 and Pagani et al 9 affirmed that no significant difference in response rate, duration, survival, and toxicity in the treatment of patients with breast cancer has been shown for toremifene and tamoxifen. In preclinical studies, toremifene has been shown to cause less DNA-adduct formation and to have less estrogenic activity in the endometrium.…”

“…Although tamoxifen is still the anti-estrogen of choice in the treatment of breast cancer patients, many clinicians consider toremifene to be a valid and safe alternative to tamoxifen in endocrine-responsive breast cancer, for similar anti-tumor effects and the possibility of a lower incidence of treatment-related endometrial malignancies. 6,[8][9][10] Toremifene is a triphenylethlene derivative related to tamoxifen. Toremifene has a high affinity for the estrogen receptor in breast cancer, is active against the breast cancer, and has an antitumor activity.…”