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Treatment of recurrent and metastatic adenocarcinoma of the endometrium with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate.

We conducted a retrospective review of 44 patients with metastatic or recurrent endometrial carcinoma treated with cisplatin, doxorubicin, cyclophosphamide, and medroxyprogesterone acetate. Thirty-six women had metastatic disease; eight had recurrent disease. In the metastatic group, 12 women had positive peritoneal cytology as the only criterion for metastatic disease. Grade 1 tumors represented 25%, grade 2, 47.7%, and grade 3, 27.3%. The series was divided into four groups based on disease volume before chemotherapy: positive peritoneal cytology only (N = 12), microscopic (N = 11), macroscopic less than 2 cm (N = 6), and macroscopic greater than 2 cm (N = 15). Fifteen patients had measurable disease and eight (53%) had an objective response. The median survival was 31 months for the whole group. Median survivals were not reached for the positive peritoneal cytology only and the microscopic groups. Median survival for the macroscopic less than 2 cm and greater than 2 cm groups were 15 and 10 months, respectively (P less than .0001). The volume of disease was the most important factor in determining survival as well as the time to progression (P less than .0001). The distribution of grade was similar in all groups (P = .88), and grade did not predict survival (P = .80) or recurrence (P = .87). The significant number of low-grade lesions in our series as well as the importance of positive cytology as a predictor of survival underscore the need for surgical pathologic staging in an effort to identify those patients in need of adjuvant therapy.

Adenocarcinoma↗

Serum lipids and lipoproteins in continuous or cyclic medroxyprogesterone acetate treatment in postmenopausal women treated with conjugated estrogens.

This study evaluates effects on serum lipids of continuous or sequential progestogens for hormonal replacement in women. Subjects received either a cyclic regimen of replacement (0.625 mg/d of conjugated equine estrogens (Es) for 25 days/month and 10 mg medroxyprogesterone acetate [MPA] for the last 13 days of E) or 0.625 mg/d E along with either 5 or 10 mg MPA (Provera, Upjohn Company, Kalamazoo, MI). Study parameters were measured over a 24-week period. No differences in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins I and II, sex hormone-binding globulin, or serum MPA levels were noted between the sequential and 5 mg continuous group. The 10 mg MPA group did not have an increase in HDL or decrease in low-density lipoprotein as did the other groups.

Adult↗

Effect of various doses of medroxyprogesterone acetate on intestinal functions in rats.

The dose relationship between medroxyprogesterone acetate (MPA), a long acting contraceptive, and rat intestinal digestive and absorptive functions has been investigated. The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight). This decrease was found to be significant (p less than 0.001) at all the doses tested. The inhibition in the intestinal uptake of calcium paralleled the decrease in alkaline phosphatase activity. Relatively high amount of MPA (140 mg/kg; 360 mumol/kg) was required to augment the uptake of glucose and amino acid. The results obtained do not indicate a close relationship between the dose of the drug and the extent of alteration in the rat intestinal digestive and absorptive functions. The study appears to confirm the association between brush border enzymes activities and uptake of nutrients in rat intestine.

Animals↗

Experience with the use of depo-medroxyprogesterone acetate in a Nigerian population.

Eight hundred and ten patients who accepted to use depo-medroxyprogesterone acetate (DMPA) for contraception were studied over a period of 11 years (1976-1986). Important side-effects observed were amenorrhoea (36.3%), weight gain (15.8%), weight loss (10.6%), metrorrhagia (6.7%) and menorrhagia (6.0%). Amenorrhoea, menorrhagia and metrorrhagia were major reasons for discontinuation of DMPA in 11% of acceptors. There were no cases of pregnancy, genital or breast malignancies during DMPA use. Our experience indicates that DMPA as a contraceptive is effective and should be available for suitable clients who demonstrate oestrogen intolerance.

Adult↗

Effects of the injectable contraceptive depot medroxyprogesterone acetate in Thai women with liver fluke infestation: results after six months.

The effect of the three-monthly injectable contraceptive depot medroxyprogesterone acetate (DMPA) on liver and lipid function was assessed in Thai women with liver fluke (Opisthorchis viverrini) infestation, DMPA administration being started in the immediate postpartum period. Immediate postpartum IUD and sterilization acceptors with fluke infestation were recruited as a comparison (control) group for the fluke-positiv DMPA acceptors. Comparable groups of fluke-negative acceptors were recruited in an area of Thailand free of liver fluke transmission. Results are presented for the first 6 follow-up months for 170 DMPA and 177 control fluke-positive subjects and for 153 DMPA and 150 control fluke-negative subjects. Small and similar increases occurred in each of the four groups for alanine amino transferase, isocitrate dehydrogenase, and total bilirubin levels while aspartate amino transferase levels changed less in the DMPA groups than in their respective control groups. None of the subjects in either DMPA group had clearly abnormal results in these tests at 6 months. Alkaline phosphatase, cholesterol, and triglycerides levels were markedly lower in each group at 6 months than in the puerperal specimens. There was a greater decrease in triglycerides levels in both DMPA groups than in their respective control groups. However, the decrease in the alkaline phosphatase and cholesterol levels was greater only in the fluke-positive DMPA group than in the fluke-positive control group. None of these biochemical results were related to differences in age, parity, or lactation status between the groups. The results indicate that DMPA did not cause any early deleterious effects in the metabolic factors studied in women with liver fluke infestation.

Adolescent↗

Endocrine effects of medroxyprogesterone acetate: relation between plasma levels and suppression of adrenal steroids in patients with breast cancer.

The elimination of adrenal steroids by adrenalectomy or medical treatment has been one of the mainstays in the palliative treatment of patients with disseminated breast cancer. Recently, the effects of progestins on adrenal function has become the subject of renewed interest. To find a relation between plasma levels of medroxyprogesterone acetate (MPA) and adrenal suppression in breast cancer patients, we compared a group of 41 postmenopausal patients with disseminated or inoperable breast cancer, treated with oral MPA, with a control group of 28 postmenopausal breast cancer patients without treatment. To obtain MPA plasma levels in the lower range, 13 patients initially received 300 mg of MPA daily (Group 1), six of whom were subsequently treated with 600 mg (Group 2). Group 3 comprised 37 patients treated with 900 mg of MPA. All of the parameters studied varied widely. Only in Group 3 patients were the MPA levels higher and the levels of cortisol, androstenedione, DHAS, and estrone lower than those in Group 1 patients. All steroid levels in Group 3 were significantly below control values. Considering all data, a negative but weak correlation was found between MPA levels and cortisol (R = -0.55), androstenedione (R = -0.58), and dehydro-epi-androsterone sulfate (R = -0.40), but not for MPA and estrone, indicating better adrenal suppression by higher MPA dosage and plasma levels. However, suppressed cortisol concentrations did not predict sufficient MPA dosage in all patients because low cortisol was not always associated with high MPA levels. A positive relation existed between the levels of androstenedione and estrone, which shows that suppression of these adrenal androgens may result in suppression of plasma estrone. This may be of additional therapeutic benefit in breast cancer patients.

Adrenal Glands↗

A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate.

The results obtained with a new hormone therapy using medroxyprogesterone acetate (MAP) in previously untested single and total doses in the treatment of advanced breast cancer are reported. Fifty-two postmenopausal patients were treated with an average total dose of 40 g of MAP for a period of 30 days. Nineteen of 44 patients (43%) had complete or partial remission, while the disease remained unchanged in nine of 44 patients (20%). Disease progression occurred in 12 of 44 patients (27%). Partial or complete remission occurred in 12 of 18 (67%) and four of six (67%) of the patients with dominant osseous and soft tissue metastases respectively. Three of ten (16%) of those with visceral metastases had remission. The average duration of remission was 7 months. Average survival times were 15.5 months for patients with remission, 8 months for those with no change, and 2.5 months for those with disease progression. From a subjective standpoint, pain was reduced significantly or disappeared in 34 of 36 patients (94%); this was also the case with respect to dyspnea (13 of 16 patients [81%]), anorexia (24 of 29 [83%]), asthenia (28 of 35 [80%]), and walking impairment (15 of 24 [63%]). When relapse occurred, patients previously treated with massive doses of MAP received further treatment with higher doses of MAP; four of 22 (18%) of the patients attained partial remission once again. Positive effects were also seen in subjective performance status, body weight, and EKG. We also describe the new clinical and toxicologic features of this treatment.

Adult↗

Inhibitory effect of medroxyprogesterone acetate on foreign body tumorigenesis in mice.

This paper reports on the investigation of the effect of medroxyprogesterone acetate (MPA) on foreign body tumorigenesis that resulted from sc implantation of a glass cylinder. Adult BALB/c mice of both sexes bearing the foreign body were separated into groups. Group 1 received 40 mg MPA sc every 2 months during 1 year, in the vicinity of the glass cylinder; group 2 received the same MPA treatment in the contralateral flank; and group 3 received no hormonal treatment. Sarcomas developed in 4 of 39, 9 of 41, and 17 of 39 mice, respectively. With the use of an evaluation based on the number of high-risk mice per time interval, the MPA inhibitory effect was found to be statistically significant in both groups: 26, 53, and 79% tumor incidence, respectively. A decrease in the rate of tumor development also was observed but only in mice treated with MPA in situ. An unexpected side effect of continuous MPA administration in females was the appearance of adenocarcinomas.

Adenocarcinoma↗

Oral versus im administration of high-dose medroxyprogesterone acetate in pretreated patients with advanced breast cancer.

In a multicenter trial, 123 patients with advanced breast cancer who had been treated with tamoxifen and/or chemotherapy were randomized to receive medroxyprogesterone acetate (MPA) orally 300 mg X 3 daily or im 500 mg daily for 4 weeks and 500 mg X 2 weekly thereafter. All case histories were reviewed extramurally by the criteria of the International Union Against Cancer. Five and 11 patients were not eligible and evaluable for response, respectively. Pretreatment characteristics were well balanced in both treated groups. Twenty-five of all 107 (23%) evaluable patients achieved an objective remission, whereas in a further 15% the disease became stable after previous progression. Results in both treatment arms did not differ significantly. The median duration of objective remission was 12 and 14 months for orally and im treated patients, respectively (P greater than 0.10). No statistically significant differences in the survival times of orally and im treated patients were found. Pretreatment characteristics positively correlated with an objective remission during MPA therapy in both groups were age greater than 50 years (P less than 0.02) and no previous chemotherapy (P less than 0.01). Toxicity included an increase in body weight, cushingoid effects, muscle cramps, and tremors in both groups. In four patients on im therapy, local infections developed. Mean serum MPA levels reached values above 100 ng/ml in nine orally and eight im treated patients (P greater than 0.10), and neither differed significantly in the patients responding to or failing therapy. In both MPA arms, plasma cortisol levels were suppressed. The drop in plasma cortisol levels was more pronounced in patients with objective remissions than in patients who failed (P = 0.04). In conclusion, oral and im MPA in the given doses had similar activity. Im administration of MPA should be reserved for patients not able to take oral medication.

Administration, Oral↗

[Treatment of true precocious puberty with medroxyprogesterone acetate].

The authors analyze the treatment of 16 female infants with true precocious puberty, ages ranging from 12 months to 9.5 years at the time of diagnosis, based on clinical and laboratory findings. All patients were treated with 150 to 300 mg. every 15 to 20 days of injectable medroxyprogesterone acetate (MPA) for periods from 5 months to 6 years. The prognosis of the adult height was evaluated before and during MPA treatment using the following parameters: height velocity as a function of bone age (good response of 15 patients); height as a function of bone age (good response of 13 patients); developmental quotient (good response of 14 patients), and adult height prognosis by the use of the tables of Bayley & Pinneau (good response of 8 out of 10 patients). The authors conclude that MPA treatment was effective in improving the prognosis of adult height in 14 out of 16 patients of true precocious puberty.

Body Height↗

Decrease of granulocyte-macrophage colony-forming units during high dose medroxyprogesterone acetate treatment in advanced breast cancer.

We treated 18 post-menopausal women with advanced breast cancer with medroxyprogesterone-acetate 1000 mg p.o. daily. The study of granulocyte-macrophage colony forming units (GM-CFU) performed monthly, and peripheral white blood cell count showed an increase of granulocytes not statistically significant and a progressive decrease of GM-CFU that could protect marrow from chemotherapeutic agents or interfere with the myelosuppression of cytotoxic drugs.

Breast Neoplasms↗

Effects of medroxyprogesterone acetate on DMBA-induced mammary tumors.

Rats with DMBA-induced mammary tumors were treated for 30 days i.m. with medroxyprogesterone acetate (MPA) at doses of 7.5, 15 or 75 mg/kg. Complete regression (disappearance of tumor) was observed in 60% and 20% of tumors from rats treated with 75 or 15 mg/kg MPA respectively. Partial regression (50% decrease in tumor area) was found in the remaining 20% of tumors from rats treated with 15 mg/kg MPA. The dose of 7.5 mg/kg MPA resulted in being devoid of effectiveness. Estrogen receptor (ER) levels were significantly reduced at all doses of MPA injected both in responsive and non-responsive tumors. However, only tumors with ER levels above 15 fmol/mg before therapy resulted in being responsive to MPA treatment. Progesterone receptors were so reduced at the end of the experiment as to not be detectable in all treated groups. It was concluded that MPA is effective as an antitumoral drug also in DMBA-induced mammary tumors and that this effect is at least in part related to ER levels before treatment.

9,10-Dimethyl-1,2-benzanthracene↗

Dexamethasone, medroxyprogesterone acetate, and vindesine modulation of human malignant melanoma growth in soft agar.

We have previously shown biopsies from human malignant melanoma, as well as a cell line (MELUR) derived from human malignant melanoma cells, to contain dexamethasone (DEX) - and medroxyprogesterone acetate (MPA) - binding macromolecules exhibiting properties of glucocorticoid receptors from well-known target organs. In this paper, we demonstrate that the cloning efficiency of MELUR melanoma cells is inhibited by DEX and MPA in a dose-dependent manner. MELUR tumour colony-forming units (MELUR-TCFU) were inhibited more than 40% by either DEX or MPA at 1 X 10(-7) mol/l with concentrations needed to obtain a 50% reduction in TCFU counts for both hormones of 3 X 10(-9) mol/l. MELUR cell growth in soft agar was also modulated by vindesine (VI). At 50 ng/ml, VI produced a 70% reduction of colony formation. The combined drug effects of either DEX or MPA and VI on colony formation were additive. The data indicate that the proliferative activity of MELUR cells is regulated by DEX and MPA, both acting additively to VI.

Antineoplastic Combined Chemotherapy Protocols↗

[The treatment of metastasizing hypernephroid (renal cell) carcinoma with medroxyprogesterone acetate (Clinovir) (author's transl].

15 patients with distant metastases of hypernephroid carcinoma were treated with medroxyprogesterone acetate (usually 300 mg daily by mouth). In 5 patients the metastases showed slower growth, remained stationary or regressed somewhat under this treatment. But a complete regression of metastases could not be obtained. The treatment was very well tolerated. Monitoring the transaminases and alkaline phosphatase during treatment is to be recommended.

Adenocarcinoma↗

[Use of medroxyprogesterone in human hepatic cirrhosis].

The effect of medroxyprogesterone in 14 patients with hepatic cirrhosis demonstrated with histological technics was studied. Eight of the 14 patients were controlled over a period of one year and three months. Six of this eight patients presented subjective clinical improvement and the ascitis disappeared in 5/7 cases, so that the doses of lactona could be diminished. Three of the male patients recovered their sexual potency although all were in alcoholic abstinence for more than one year. Histologically 5/6 patients presented a diminishing fibrosis in the control biopsy and the 3 patients controlled with hemodynamic studies presented lower portal pression. We didn't found secondary effects, except obesity in 3 cases. We concluded that it would be important to continue this experience with a greater number of patients and adding appropriate biochemical controls.

Adult↗

Phase II study of aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer.

Forty-five women with far-advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG), 1000 mg p.o. daily, and medroxyprogesterone acetate (MPA), 1500 mg p.o. daily. Of 41 patients evaluable for treatment response, there were two complete responses, five partial remissions, 26 patients with minor tumor responses or no change, and eight nonresponders. Major side effects included those known for AG and MPA, i.e., impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, changes in body weight, and transient increase of gamma-glutamyl-transferase. Most side effects disappeared spontaneously after 4 to 6 weeks of treatment. Plasma hormone measurements in 28 patients revealed no impairment of adrenocorticotropic hormone and cortisol levels. In conclusion, in the AG combination, it is feasible and safe to replace cortisol by MPA. Treatment results warrant further investigation of AG-MPA in patients with breast cancer of a more favorable prognosis.

Adrenocorticotropic Hormone↗

Effect of medroxyprogesterone and an aorta-derived cell growth inhibitor on B16 melanoma in mice.

An aorta-derived inhibitor of endothelial cell and tumor cell growth and medroxyprogesterone, which depresses collagenase expression in vivo, were tested alone and in combination against B16-F10 melanoma in C57BL/6 mice in such doses that either agent alone had little effect. Together, these agents retarded growth of subcutaneously transplanted tumor cells and reduced the number and size of pulmonary tumors after iv tumor cell injection. Of the treatments used, only the aortic factor administered alone prolonged life in mice with pulmonary tumors.

Animals↗

Liver function and medroxyprogesterone acetate elimination in man.

Medroxyprogesterone acetate (MPA) elimination rate was investigated in 25 patients with primary biliary cirrhosis, alcoholic cirrhosis and fatty liver. The serum and urine concentrations of MPA were measured by RIA after a single oral administration of the drug. Biochemical liver tests and antipyrine kinetics were determined as indicators of the liver function. The antipyrine test, a reflector of the activity of hepatic drug-metabolizing enzyme system, was impaired only in alcoholics. The results demonstrate that the elimination rate of MPA is reduced in subjects with alcoholic cirrhosis, whereas the values of the patients with fatty liver and primary biliary cirrhosis are in the normal range. The findings show that the MPA elimination is impaired only in cases with far advanced liver disease.

Antipyrine↗