Antiestrogenic and antitumor properties of the new triphenylethylene derivative toremifene in the rat

Salle, E. Di; Zaccheo, T.; Ornati, G.

doi:10.1016/0022-4731(90)90005-d

Cited by 63 publications

(23 citation statements)

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“…Previous data on tamoxifen were extended by the finding that a novel antioestrogen, toremifene, preserved bone mass as effectively as tamoxifen, although experimental data havo shown it to be less oestrogenic than tamoxifen (Di Salle et al, 1990). Clodronate provided an additional benefit for post-menopausal breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Saarto

Blomqvist²,

Välimäki³

et al. 1997

Br J Cancer

115

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Summary The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.Keywords: antioestrogens; bone mineral density; bisphosphonate; breast neoplasm; post-menopausal osteoporosis; toremifene Adjuvant antioestrogen treatment with tamoxifen significantly improves the survival of post-menopausal women with primary breast cancer (EBCTCG, 1992). Tamoxifen has oestrogen agonistic effects on bone and therefore prevents bone loss in postmenopausal women (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Powles et al, 1996). Tamoxifen has been shown to prevent bone loss predominantly in the lumbar spine (Love et al, 1992;Kristensen et al, 1994), but in two randomized studies this was also true for the upper femur (Ward et al, 1993;Powles et al, 1996).Toremifene is a close analogue to tamoxifen with demonstrated efficacy in advanced breast cancer (Valavaara et al, 1988). Compared with tamoxifen, toremifene is more oestrogen antagonistic than agonistic in rat (Di Salle et al, 1990). At present, no data are available on the effect of toremifene on bone.Since bisphosphonates prevent post-menopausal bone loss (Chesnut 1984; Reginster et al, 1989;Storm et al, 1990;Watts et al, 1990;Giannini et al, 1993;Harris et al, 1993;Reid et al, 1994;Filipponi et al, 1995;Liberman et al, 1995) and in advanced breast cancer reduced the development of new bone metastases (Elomaa et al, 1983;Martoni et al, 1991;Paterson et al, 1993;Van Holten Verzantvoort et al, 1993), they are attractive candidates for the treatment of patients with early breast cancer. We performed a prospective, open, randomized study to determine the effect of oral clodronate in post-menopausal women with primary breast cancer treated with adjuvant antioestrogens, Received 24 July 1996 Revised 10 October 1996 Accepted 15 October 1996 Correspondence to: Elomaa, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Hels...

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Section: Discussionmentioning

confidence: 99%

“…Compared with tamoxifen, toremifene is more oestrogen antagonistic than agonistic in rat (Di Salle et al, 1990). At present, no data are available on the effect of toremifene on bone.…”

mentioning

confidence: 99%

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Saarto

Blomqvist²,

Välimäki³

et al. 1997

Br J Cancer

115

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“…Therefore, toremifene was a valid change for tamoxifen. Some studies [24,25] suggested that toremifene had a lower estrogenicto-antiestrogenic ratio than tamoxifen, which might explain the differences of thromboembolic events between the two drugs. When severe adverse effects occurred during the use of tamoxifen, toremifene may be considered.…”

Section: Discussionmentioning

confidence: 98%

Toremifene is an effective and safe alternative to tamoxifen in adjuvant endocrine therapy for breast cancer: results of four randomized trials

Zhou

Ding

Chen

et al. 2011

Breast Cancer Res Treat

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Compared to tamoxifen, the efficacy and side effects of toremifene in adjuvant endocrine therapy for breast cancer were not very clear. This meta-analysis was conducted to give a more precise estimation of the efficacy and severe side effects of toremifene given in the adjuvant setting in comparison to tamoxifen. The electronic database PubMed was searched for randomized trials comparing toremifene with tamoxifen as adjuvant therapies. Four randomized trials published in three articles were eligible, including 1,890 pooled cases treated with toremifene and 1,857 cases treated with tamoxifen. Compared to patients in tamoxifen group, patients in toremifene group did not have a significantly different overall survival rate (risk ratio (RR): 1.07, 95% confidence interval (CI): 0.97-1.19, P = 0.994 for heterogeneity) or a disease-free survival (DFS) rate (RR: 1.05, 95% CI: 0.95-1.17, P = 0.431 for heterogeneity) at the end of the follow-up time. The rates of thromboembolic events in toremifene group, including deep vein thrombosis (odds ratio (OR): 0.68, 95% CI: 0.40-1.17, P = 0.926 for heterogeneity), cerebrovascular accident (OR: 0.59, 95% CI: 0.32-1.09, P = 0.438 for heterogeneity), and pulmonary embolism (OR: 0.91, 95% CI: 0.42-2.01, P = 0.618 for heterogeneity), were not significantly different from those in tamoxifen group. The rates of endometrial polyps and endometrial cancer between the two groups were almost the same. This meta-analysis suggested that toremifene was as effective as tamoxifen in the adjuvant setting for both perimenopausal and postmenopausal breast cancer patients with similar severe adverse effects to tamoxifen. Toremifene was a convincing and safe change for tamoxifen in adjuvant endocrine therapy.

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“…Droloxifen zeigte in Tierversuchen nach einer 4monatigen Therapie einen Anstieg von Uterusgewicht und -grösse im Vergleich zu einer Kontrollgruppe [22]. Ebenso konnte in Zellkulturstudien [23] und in Tierversuchen mit Toremifen [24] eine ähnliche agonistische Wirkung, auf das Endometrium, wie bei Tamoxifen nachgewiesen werden. Was Idoxifen betrifft, zeigten sich ähnliche Ergebnisse wie bei den anderen Tamoxifenderivaten, wobei im Tiermodell eine Endometriumatrophie beschrieben wurde [25,26].…”

Section: Theoretische Grundlagen Der öStrogenaktivität Von Sermsunclassified

Wirkung von selektiven Östrogen-Rezeptor-Modulatoren auf östrogensensitive Gewebe

Jirecek

Pávó²,

Huber³

1999

Gynäkol Geburtshilfliche Rundsch

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Selektive Östrogen-Rezeptor-Modulatoren (SERMs) agieren ausschliesslich über den Östrogenrezeptor und haben gewebespezifische und agonistische und antagonistische Eigenschaften. Alle beschriebenen SERMs haben im Knochen und im kardiovaskulären System einen östrogenen Effekt: Sie hemmen den postmenopausalen Verlust der Knochendichte und beeinflussen positiv Plasmalipoproteine und einige Gerinnungsfaktoren. Das Ziel dieser Arbeit ist es, die Wirkungsweisen der SERMs in den östrogenabhängigen Geweben Brust und Endometrium zu beschreiben. Es gibt, abhängig von deren chemischer Struktur, zwei Typen von SERMs, die klinisch erprobt sind: die Triphenyläthylene und die Benzothiophene. Tamoxifen ist der Prototyp der SERMs mit der Struktur der Triphenyläthylene. Tamoxifen, wie alle anderen SERMs, ist im Brustgewebe ein Östrogenantagonist und wird weltweit zur adjuvanten Behandlung von Brustkarzinomen eingesetzt. Neue Arbeiten weisen auf die Fähigkeit von Tamoxifen hin, bei Risikopatientinnen Brustkrebs verhindern zu können. Wegen der partiellen östrogenen Wirkung von Tamoxifen auf das Endometrium kommt es in der Praxis zu einer Endometriumhypertrophie und zu einem erhöhten Endometriumkarzinomrisiko. Andere SERMs mit der gleichen Struktur, Droloxifen, Toremifen und Idoxifen, könnten bei der Behandlung von Brustkarzinomen ähnlich wie Tamoxifen einsetzbar sein. Vorteile der neuen SERMs mit triphenyläthylener Struktur könnten eine verminderte agonistische Wirkung auf das Endometrium und ein verbessertes toxikologisches Profil sein. Raloxifen, ein Benzothiophen, hat eine andere chemische Struktur als die Triphenyläthylene und besitzt eine ihnen ähnliche antagonistische Wirkung auf das Brustgewebe. Klinische Studien mit Raloxifen zeigten bei postmenopausalen Patientinnen mit Osteoporose eine signifikante Verringerung von neu diagnostizierten Brustkarzinomfällen im Vergleich zu Plazebo. Im Gegensatz zu Tamoxifen konnte in klinischen Studien mit Raloxifen kein stimulierender Effekt auf das Endometrium festgestellt werden.

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Antiestrogenic and antitumor properties of the new triphenylethylene derivative toremifene in the rat

Cited by 63 publications

References 9 publications

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Toremifene is an effective and safe alternative to tamoxifen in adjuvant endocrine therapy for breast cancer: results of four randomized trials

Wirkung von selektiven Östrogen-Rezeptor-Modulatoren auf östrogensensitive Gewebe

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