High Dose Medroxyprogesterone-Acetate Treatment in Advanced Mammary Carcinoma: A Phase II Investigation

Mattsson, W.

doi:10.3109/02841867809128249

Cited by 30 publications

(4 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings should be borne in mind when progestins are used in high doses as, for example, in the therapy of hormone-dependent breast tumours (15 mg/kg in the rat correspond to 825 mg in a woman of 55 kg body weight; Mattson, 1978;Pannuti, Martoni, Lenaz, Piana & Nanni. 1978).…”

Section: Discussionmentioning

confidence: 95%

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

Carlo¹,

Gallo²,

Conti³

et al. 1983

Journal of Endocrinology

View full text Add to dashboard Cite

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol-receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

show abstract

Section: Discussionmentioning

confidence: 95%

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

Carlo¹,

Gallo²,

Conti³

et al. 1983

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Previous studies of high-dose MPA in advanced breast cancer have reported response rates ranging from 28% (Mattson, 1978) to 46% (Pannuti et al, 1979) in patients who had not previously received cytotoxic therapy and this figure has risen to over 70% when patients were selected according to oestrogen-receptor status (Mattson, 1980 Interpretation of the levels at and beyond this time is obscured by dose reductions, due to toxicity, and the fall off in the numbers of non-responders due to patients coming off treatment because of progressive disease. The shape of the curves for the two patient groups suggests that the responders may have been slower metabolisers of MPA, thus rapidly achieving high blood levels, and the possibility of there being different patterns of MPA metabolism which might be of therapeutic significance merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

An evaluation of high-dose medroxyprogesterone acetate (MPA) therapy in women with advanced breast cancer

Johnson¹,

Priestman²,

Fotherby³

et al. 1984

Br J Cancer

View full text Add to dashboard Cite

Summary The efficacy of high-dose intramuscular MPA therapy in controlling progressive measurable metastatic breast carcinoma was assessed in 32 women. In addition serial measurements of MPA blood levels were carried out in 20 of the patients and subjective effects of treatment were monitored in detail in 18 of the women. Overall 6 patients (19%) gained an objective response and a further 7 (22%) experienced disease stasis from 4-17 months whilst on treatment. Significant differences in serum MPA levels were seen between responders and non-responders, objective tumour shrinkage only being seen in those patients who rapidly attained, and sustained, blood levels in excess of 100ngml-1. Subjective assessment showed no evidence of a euphoriant effect of MPA therapy in the non-responders group.Reports of high-dose Medroxyprogesterone acetate (MPA) administration in the treatment of advanced breast cancer began to appear in the mid 1970s and in 1979 a review of the published data concluded that an objective remission rate of 40% was seen in women who had not previously received cytotoxic therapy (Ganzina, 1979). In addition to objective benefit the relative lack of toxicity of MPA combined with its ability to relieve pain (Pannuti et al., 1979), improve performance status (Ganzia, 1979), and increase appetite and body weight (Cavalli et al., 1983) led to the view that treatment carried a significant subjective benefit. Clinical trials showed that daily intramuscular doses of MPA of 500 mg or more were necessary for a significant incidence of response (Ganzina, 1979), but pharmacokinetic studies have indicated considerable differences in bioavailability between patients (Salimtschik et al., 1980). The present study set out across the objective response to high-dose MPA in women with advanced breast cancer and also to monitor both serum MPA levels and subjective effects of treatment in order to identify any correlations between these three parameters. Materials and methodsThe study was designed as an open, single group assessment and women with evaluable, progressing, locally recurrent or metastatic carcinoma of the breast which had failed to respond to, or relapsed after, conventional therapy were enrolled. Objectives response was assessed at monthly intervals and UICC criteria were adopted (Hayward et al., 1977

show abstract

“…were introduced, response rates went up to over 40% (2,3), but the treatment sometimes caused gluteal abcess or induration because of daily i.m. injections (4,5,6,7). In order to administer the drug easily and to avoid the side effects, we have tried oral high-dose MAP for Japenese patients with advanced breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer

Izuo

Iino

Endo

1981

Breast Cancer Res Tr

View full text Add to dashboard Cite

Medroxyprogesterone acetate (MAP) in the treatment of advanced breast cancer has been regarded as a minor agent according to the previous reports when used at low doses (less than 500 mg/day). High doses of more than 500 mg which have come into use since 1973 give a response rate of over 40%, but sometimes cause gluteal abscess or induration because of daily intramuscular injections. In order to administer easily and to avoid the side effect, we have attempted to use oral administration in a daily dose of 1200 mg (400 mg X 3). Of those 20 patients treated with oral high-dose MAP, 1 showed complete response, 6 showed partial response, 7 no change, and 6 progressive disease. As for site of lesion, 4 out of 6 (67%) in skin and 4 out of 16 (25%) in bone responded. Neither severe side effects nor abnormal laboratory data were seen. Then, we examined the blood levels of MAP in vivo by RIA in 9 patients. The blood level of MAP reached 39-250 ng/ml in 3 days and was maintained at least over 50 ng/ml for 1 or 2 months of continuous administration. Subsequently, we examined the effects of MAP on binding to ER in vitro. The inhibition of binding of estradiol-17 beta to ER was about 60% at 10(-5) M MAP. The blood level of 50 ng/ml in vivo corresponds to about 1.3 X 10(-5) M.

show abstract

High Dose Medroxyprogesterone-Acetate Treatment in Advanced Mammary Carcinoma: A Phase II Investigation

Cited by 30 publications

References 39 publications

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

An evaluation of high-dose medroxyprogesterone acetate (MPA) therapy in women with advanced breast cancer

Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer

Contact Info

Product

Resources

About