Treatment of Advanced Breast Cancer with Progestins: A review

Løber, J.; Rose, Carsten; M, Salimtschik; Mouridsen, Henning T.

doi:10.3109/00016348109157810

Cited by 28 publications

(11 citation statements)

References 40 publications

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“…Some trials (Castiglione-Gertsch et al, 1993) suggested that tamoxifen's primacy may be challenged particularly by the use of progestogens in patients suffering from bone metastases (Muss et al, 1988;Muss et al, 1990;Castiglione-Gertsch et al, 1993;Gill et al, 1993). In those trials, as already observed, the dose of progestogen (Mattson, 1980;Löber et al, 1981;Cavalli et al, 1984;Tchekmedyian et al, 1986;Van-Veelen et al, 1986) could be of paramount for determining the antitumor efficacy of these agents: high doses of drugs could significantly increase the response rate and even, in some observations, prolong time to treatment failure and survival (Mattson, 1980;Löber et al, 1981;Cavalli et al, 1984;Tchekmedyian et al, 1986;Van Veelen et al, 1986). Furthermore, like first-line hormonotherapy for advanced ER positive breast cancers, in premenopausal patients, HD-MPA developed antitumour activity at least equivalent, if not superior, to oophorectomy (Martoni et al, 1991).…”

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“…Comparative evaluations of the relative efficacy of tamoxifen and progestogens (especially at high dosages) provided evidence of an at least equipotent or even better antitumoural activity of the progestogens (Mattson, 1980;Löber et al, 1981;Van Veelen et al, 1986;Muss et al, 1988;Muss et al, 1990;Castiglione-Gertsch et al, 1993;Gill et al, 1993).…”

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“…Moreover, after having crossed-over, progestogens retained some antitumour efficacy after tamoxifen's failure (Mattson, 1980;Löber et al, 1981;Van Veelen et al, 1986;Muss et al, 1988;Muss et al, 1990;Castiglione-Gertsch et al, 1993;Gill et al, 1993). Some trials (Castiglione-Gertsch et al, 1993) suggested that tamoxifen's primacy may be challenged particularly by the use of progestogens in patients suffering from bone metastases (Muss et al, 1988;Muss et al, 1990;Castiglione-Gertsch et al, 1993;Gill et al, 1993).…”

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“…The addition of medroxyprogesterone acetate in high dosage (i.e. at least 500 mg day -1 ) to combined chemotherapy also enhanced initial tumour shrinkage and perhaps prolonged survival in advanced breast carcinoma (Robustelli Della Cuna et al, 1980;Löber et al, 1981).…”

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“…Although the action of progestins, such as high-dose medroxyprogesterone acetate (HD-MPA), can be explained by interacting with oestrogens, either by inhibition of gonadotrophin secretion or down-regulation of the oestrogen receptors, they may also have a direct inhibitory effect on tumour cell growth after binding to progesterone receptors (Löber et al, 1981;Blossey et al, 1984;Paridaens et al, 1986;Rubens, 1993;Hyder et al, 1998). HD-MPA induces a significant blockage of the hypothalamo-hypophysogonadal and adrenal axes (Blossey et al, 1984;van Veeler et al, 1985).…”

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Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

et al. 2001

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SummaryThe authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years. Previous results were confirmed in this analysis on mature data. In NN patients, relapse-free survival (RFS) was improved in the adjuvant hormonotherapy arm, regardless of age while overall survival (OAS) was also increased in younger (less then 50 years) patients. In the whole group of NP patients, no difference was seen regarding RFS or OAS. However, an age-dependant opposite effect was observed: younger patients (< 50) experienced a worse and significant outcome of relapse-free and overall survivals when receiving adjuvant HD-MPA while older patients (> = 50) enjoyed a significant improvement of their relapse-free survival. For both NN and NP patients, differences in overall survivals observed in older women with a shorter follow-up, were no longer detected.

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Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

et al. 2001

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Additive hormonal therapy in women with advanced breast cancer

Ingle

1984

Cancer

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A great deal of work has been done over the last decade in the assessment of additive hormonal treatment approaches in women with advanced breast cancer. This work has been prompted by a number of factors which include: (1) the introduction of new hormonal agents, (2) increased knowledge of the physiologic actions of several hormonal agents, (3) the development of hormonal receptor assays to better predict the probability of hormonal responsiveness in a given patient, and (4) the apparent plateau in efficacy of cytotoxic chemotherapeutic approaches. The hormonal agents that have been studied most extensively in the recent past include tamoxifen (an antiestrogen), aminoglutethimide (an aromatase inhibitor), and medroxyprogesterone acetate (a progestin). In postmenopausal women, several agents exist that appear about equal in efficacy; but, currently, tamoxifen appears to be preferred as the initial hormonal treatment, primarily because of its low incidence of side effects. Studies involving combination hormonal therapy have produced interesting results, but further work is needed to establish superiority over tamoxifen alone. In premenopausal women, tamoxifen does have antitumor activity in some patients but has not been established as a replacement for oophorectomy. Properly conducted comparative trials will remain essential for the determination of the proper place of newer hormonal therapy approaches in clinical practice.

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Oral high‐dose medroxyprogesterone acetate versus tamoxifen: A randomized crossover trial in postmenopausal patients with advanced breast cancer

Veelen¹,

Willemse

Tjabbes³

et al. 1986

Cancer

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In a prospective randomized multicenter study in previously untreated postmenopausal patients with advanced breast cancer, the response to treatment with oral medroxyprogesterone acetate (MPA) 300 mg three times daily was compared with tamoxifen (TAM) 20 mg twice daily. Of 61 patients treated with MPA, 27 (44%) had a partial or complete remission, 6 showed no change, and 28 had progressive disease. Of 68 patients treated with TAM, 24 (35%) showed a remission, 15 no change, and 29 progression. The difference in response rate is not significant. However, 11 of 25 patients with osseous metastases as predominant site, responded to MPA and 7 of 31 to TAM (P = 0.05). Moreover, in patients older than age 70 years, 13 of 26 responded to MPA and 6 of 31 to TAM (P less than 0.05). Median duration of remission of all patients in the MPA arm was 17 months and in the TAM arm, 23 months (not significant). Median survival was 20 months for MPA and 26 months for TAM (not significant). After cross-over from TAM to MPA 8 of 31 patients responded and after cross-over from MPA to TAM, no response was seen in 27 patients. These data indicate that the response rate and duration to MPA and TAM are comparable, except in patients with osseous metastases and in patients older than age 70 years. MPA has more side effects, but seems to be more effective after cross-over, and may thus be reserved for second-line treatment.

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Treatment of Advanced Breast Cancer with Progestins: A review

Cited by 28 publications

References 40 publications

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

Additive hormonal therapy in women with advanced breast cancer

Oral high‐dose medroxyprogesterone acetate versus tamoxifen: A randomized crossover trial in postmenopausal patients with advanced breast cancer

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