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

Abstract

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.

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect

“…Although the efficacy of MPA has been reported to be comparable or superior to that of tamoxifen, a non-steroidal anti-oestrogen, tamoxifen has been recognized as a first-line endocrine therapeutic agent because of fewer adverse effects (Van Veelen et al, 1986). One of the main adverse effects of MPA is weight gain of patients.…”

“…One of the adverse effects of MPA is bodyweight gain of the patients (Van Veelen et al, 1986). It has been reported, however, that concomitant administration of MPA reduces the nausea and anorexia induced by the administration of cytotoxic agents, and subsequently reverses bodyweight loss (Tominaga et al, 1994).…”

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

“…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).…”

“…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).…”

“…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).…”