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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen (ICI46,474) is a competitive inhibitor of estrogen action which has found ubiquitous application in the treatment of breast cancer. The drug is the front line endocrine therapy for breast cancer and is the proven treatment of choice for the adjuvant therapy of postmenopausal women with node-positive disease. Tamoxifen is available for the treatment of premenopausal patients with advanced disease, and is being evaluated in clinical trials as an adjuvant therapy for premenopausal patients with either node-positive or node-negative disease. Laboratory studies demonstrate that tamoxifen is a tumoristatic agent and long-term treatment strategies (chemosuppression) should be considered to apply the antiestrogen to its maximal therapeutic advantage. Optimal therapy with tamoxifen may also be achieved by treatment strategies to lower circulating estrogen levels in the premenopausal patient. Tamoxifen is a well tolerated drug, and long-term therapy does not appear to induce metabolic tolerance. Concerns about premature osteoporosis or cardiovascular disease appear to be unfounded because tamoxifen has an appropriate level of target site-directed estrogenic activity. Isolated reports about the growth or appearance of endometrial carcinoma during long-term adjuvant tamoxifen therapy must be balanced against the risks of withholding treatment to patients with a fatal disease.
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PMID:Long-term adjuvant tamoxifen therapy for breast cancer. 219 41

Tamoxifen citrate has recently been shown to be effective palliative therapy in advanced endometrial carcinoma. Flare reactions from tamoxifen are well known in treatment of metastatic breast carcinoma and are not an indication for stopping therapy. We report a patient being treated with tamoxifen for advanced endometrial cancer who developed acute abdominal pain as a manifestation of a flare reaction and the significance of this observation.
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PMID:Tamoxifen flare in advanced endometrial carcinoma. 257 57

The mechanism of action of sex steroid hormones on endometrial carcinoma was analyzed by a cell culture system. 1) Estrogenic actions such as enhancement of ALP activity, PR level and cellular growth were confirmed in Ishikawa endometrial carcinoma cells which possess ER. 2) ER and PR are both localized immunocytochemically in the nuclei of Ishikawa cells, confirming the correctness of Gorsky and Greene's theory in endometrial carcinoma. 3) In Ishikawa cells with PR, progestins stimulated E2DH activity and glycogen synthesis and reduced ER level, thus proving the existence of their hormonal action. We cannot, however, rule out the pharmaceutical action of progestin, because a decrease in nucleic acid syntheses and ALP activity, alteration in electron microscopic observation and finally cellular death were observed in endometrial cancer cells without PR. 4) Conversely, Tamoxifen, anti-estrogen, stimulated the cellular growth in serum-free environment of culture. We must therefore be careful in using it clinically.
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PMID:[Mechanism of action of endocrine therapy of endometrial carcinoma]. 273 78

Forty-nine patients with advanced/recurrent endometrial carcinoma were treated with Tamoxifen, 20 mg, twice daily. There were six complete and four partial responses (response rate = 20%). The median survival of responders was 34 months compared to 6 months in nonresponders. Toxicity was minimal.
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PMID:Tamoxifen therapy in advanced/recurrent endometrial carcinoma. 290 43

Forty-six eligible women with metastatic endometrial cancer were randomly allocated to receive monthly cycles of either CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or CAF plus Provera 200 mg daily for 3 weeks followed cyclically by Tamoxifen 20 mg daily for 3 weeks. Overall response rates of 15 and 43% were seen with CAF and CAF plus hormonal therapy. Using a multivariate analysis of the results, this difference is significant (P value 0.05). In 8 patients with operable endometrial cancer, negative estrogen receptor concentration (ER less than 15 fmole/mg protein) and Grade 3 disease, the clinical course was aggressive in 4 patients with systemic and local relapse. In 10 other similar patients (negative ER and Grade 3) who received adjuvant cyclical hormonal therapy only 1 relapsed and the other 9 are disease-free for an average of more than 31 months. Sequential cyclical hormonal therapy with ER and progesterone receptor analysis has a place in the management of endometrial carcinoma.
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PMID:Efficacy of sequential cyclical hormonal therapy in endometrial cancer and its correlation with steroid hormone receptor status. 297 97

Medroxyprogesterone acetate (MPA) is used as an adjuvant hormonal medication in patients with different kinds of carcinomas. Since adequate serum levels are thought to be essential we determined the individual, postoperative MPA levels in 36 patients with endometrial carcinoma over a period of 12 weeks. The patients received either an oral dose of 3 X 100 mg MPA or a weekly changing scheme with 2 X 10 mg Tamoxifen and 3 X 100 mg MPA. An additional small group of 4 patients with ovarian carcinoma was enrolled receiving an oral dose of 1000 mg MPA daily. The peripheral serum levels of MPA exhibit enormous inter- and intraindividuell variations and only the high dosage schemes yield levels above 90 ng/ml which are claimed necessary by some authors. The cortisol concentration measured at the same time were within the normal range and did not correlate with the MPA values.
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PMID:[The medroxyprogesterone acetate serum level following various medroxyprogesterone acetate dose schedules in gynecologic oncology]. 297 43

The interactions of an antiestrogen (tamoxifen) and a progestin (medroxyprogesterone acetate) on endometrial 17 beta-hydroxysteroid dehydrogenase activities were studied in short-term experiments (four to 96 hours) in normally menstruating women at the follicular phase and were related to simultaneously measured concentrations of cytosol and nuclear estrogen and progestin receptors. Tamoxifen effected a decrease in the activity of 17 beta-hydroxysteroid dehydrogenase. This was associated with an apparent translocation to and retention of estrogen receptor in the nucleus without any significant changes in cellular progestin receptor. Medroxyprogesterone acetate administration led to a rapid increase in endometrial 17 beta-hydroxysteroid dehydrogenase activity, and depletion of cytosol and total cellular progestin receptor. Combination of the drugs led to effects that could be addressed to the individual drugs separately, and under the experimental conditions the effects of medroxyprogesterone acetate were uninfluenced by simultaneous tamoxifen administration. Put together with the authors' previous findings on the same parameters during long-term (three-week) medroxyprogesterone acetate administration, it seems possible that potentiation of progestin effects on endometrial carcinoma is not to be expected during long-term simultaneous antiestrogen-progestin treatment. It is therefore likely that the favorable effects of combining these two drugs in long-term treatment are due to their different endocrine action mechanisms.
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PMID:Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium. 299 80

Tamoxifen is an effective therapy for advanced breast cancer and is well tolerated. In elderly patients or in those with inoperable primary disease tamoxifen is as effective as surgery or radiotherapy. In early breast cancer tamoxifen is associated with a prolongation of disease-free and overall survival, at least in women over the age of 50 with nodal involvement. Major trials now suggest that the effectiveness of tamoxifen may, however, be independent of age, menopausal status and of nodal status, but this remains the subject of substantial controversy. These trials also suggest that longer periods of tamoxifen treatment (more than 2 years) are better than shorter treatments and, therefore, adjuvant tamoxifen until recurrence may be the final treatment of choice for such patients. Tamoxifen is also effective in the treatment of endometrial cancer; however, there seems little advantage in combining the drug with progestogens, either concurrently or sequentially. Modest clinical benefit has been seen in patients with ovarian cancer treated with tamoxifen but the majority of patients have been heavily pretreated. Clinical trials of tamoxifen as primary therapy for this disease are warranted. Tamoxifen has probably been the most widely studied endocrine therapy for breast cancer and the subject of some of the longest and best controlled studies. Although there is no doubt that tamoxifen is effective in adjuvant therapy of breast cancer, the precise position and duration of treatment remains to be defined unequivocally. Future use in the treatment of women at high risk of developing breast cancer--so-called prophylactic therapy--depends on improvements in risk factor determination and a continuing evaluation of the possible clinical relevance of findings in animals given long-term treatment with high doses of the drug.
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PMID:Anti-oestrogens in the treatment of breast and gynaecological cancers. 306 63

Studies of chemotherapy in advanced or recurrent gynecologic cancer have focussed on ovarian, cervical, and endometrial carcinoma. For celomic epithelial carcinomas of the ovary, a large number of cytotoxic agents have been shown to be active. Dramatic improvement in frequency of response with lesser improvement in survival has been noted with the use of cisplatin-based combination chemotherapy as compared to single alkylating agents. More recent studies have evaluated alternative ways to employ cisplatin: higher dose schedules, intraperitoneal administration, and platinum compounds with a potentially better therapeutic index. None has yet been shown superior to a combination of relatively low-dose cisplatin plus an alkylating agent with or without doxorubicin. Cisplatin remains the best studied and most active single agent in patients with squamous cell carcinoma of the cervix. While a number of other agents have demonstrated moderate activity, no combination of drugs has as yet proved superior to single-agent cisplatin. In endometrial carcinoma, progestins and doxorubicin are the most active agents. Tamoxifen, cisplatin, and hexamethylmelamine appear to have moderate activity. No combination has yet been shown to be superior to single agents. Information on chemotherapy for less common gynecologic malignancies is largely anecdotal. Two observations are of note. Cisplatin-based combination chemotherapy is highly active against germ-cell neoplasms of the ovary. Cisplatin also has definite activity against mixed mesodermal sarcoma of the uterus.
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PMID:Chemotherapy for advanced or recurrent gynecologic cancer. 330 70

It is correct to add hormone or chemotherapy in advanced metastatic disease of endometrial carcinoma and in recurrences. Large doses of hormone treatment have to be given. These are progestagens and the success rate with them, no matter which product is used, is approximately 30%. The use is limited by high blood pressure and the risks of vascular complications and metabolic upsets. Tamoxifen seems to the better tolerated and gives similar results. The response to hormone treatment depends on how sensitive the tumor is to the hormones. It is better when it has large numbers of progesterone receptors and it is of low grade. When the tumour is resistant to hormones, chemotherapy with cytotoxic drugs should be used. These drugs are adriamycine and mono or combined chemotherapy, but there is no protocol as yet that is better than any other. The debate about whether to use adjuvant treatment in stage I or II cases is open. It must be considered when the prognosis seems to be bad or there seem to be large risks of recurrences.
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PMID:[Hormone therapy and chemotherapy of endometrial cancer]. 333 Jul 33


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