Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-eight advanced breast cancer patients, most of whom had had prior treatment, were treated with the synthetic antiestogen tamoxifen. The overall objective response rate was 27% (21/78). An additional 19% (15/78) showed disease stabilization. Sixty-seven percent (14/21) of the responses were in soft tissue sites, 24% (5/21) on bony sites and one each occurred in liver and nodular lung disease. Forty percent of patients with soft-tissue disease alone responded, while less than 10% of patients with visceral disease showed responses in visceral sites. The response rate was 28% among patients with a known positive estrogen receptor (ER) assay. It was 21% among patients who had previously received cytotoxic drugs. Toxicity was mild and was seen in nausea and vomiting, hot flushes and vaginal bleeding, and occasional myelosuppression. One patient was withdrawn from the study because of a rash. In two patients the disease flared, once with concomitant hypercalcemia. Tamoxifen is a useful agent for advanced breast cancer even in some patients with visceral disease.
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PMID:Phase-II trial of tamoxifen in advanced breat cancer. 53 27

Tamoxifen (NSC-180973), a synthetic antiestrogen, was studied for efficacy and toxicity in patients with metastatic breast adenocarcinoma. Two dose levels were used, 10 mg bid and 15 mg/m2 bid, in separate groups. In the 10-mg bid dosage group, 30 of the 31 patients were considered evaluable for efficacy. Five complete and 11 partial responses were recorded, for an overall response rate of 53%. In the 15-mg/m2 bid dosage group, 44 of the 45 patients were considered evaluable for efficacy. Three complete and 16 partial responses were recorded, for an overall response rate of 43%. All 76 patients were evaluated for toxicity. Side effects were generally mild, consisting mostly of hot flushes, transient leukopenia, transient thrombocytopenia, nausea, and fluid retention. A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the test as a means to select patients for tamoxifen treatment. The conclusion from this study is that tamoxifen used as a single agent is an effective drug with minimal toxicity for treatment of metastatic breast adenocarcinoma.
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PMID:Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. 79 26

An 'anti-oestrogen' such as tamoxifen may protect prophylactically against breast cancer. At the Royal Marsden Hospital, the blind randomised feasibility study of tamoxifen 20 mg per day versus placebo in 200 healthy women has been extended into a pilot trial. A total of 435 women with a family history of breast cancer have been accrued. Compliance, acute toxicity, clotting factors, lipids and bone mass were assessed. The pilot trial has confirmed the findings of the feasibility study. Compliance was high and the frequency of side-effects was similar in both groups, except for a significant increase in hot flushes in the tamoxifen-treated women (33 vs. 17%). Bone mass and clotting factors were not affected. Tamoxifen significantly reduced serum cholesterol, low-density lipoprotein cholesterol (LDLC) and apolipoprotein B levels in post-menopausal women. In premenopausal women, the effects on lipids and lipoproteins was smaller with a significant fall in total serum cholesterol and LDLC only. The trial has approval to accrue up to 1000 women.
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PMID:Prevention of breast cancer with tamoxifen--an update on the Royal Marsden Hospital pilot programme. 214 54

Tamoxifen, a non-steroidal antioestrogen, represents a significant advance in treatment of female breast cancer. In trials of tamoxifen as postsurgical adjuvant treatment of early breast cancer, disease-free survival is consistently prolonged, representing an enhanced quality of life in association with tamoxifen's favourable adverse effect profile. Moreover, overview analysis indicates a survival benefit of approximately 20% at 5 years for all women, most clearly evident in women over 50 years, while a survival benefit independent of menopausal, nodal or oestrogen receptor status has been demonstrated in some individual trials. Thus, for postmenopausal women, tamoxifen is clearly optimal adjuvant treatment, although the relative benefit of adjuvant chemotherapy in node-negative patients requires clarification. A survival benefit for women under 50 has not been clearly demonstrated in overview analysis, but is not precluded by these rather limited data, and adjuvant treatment of premenopausal women with tamoxifen may also warrant serious consideration. Response rates to tamoxifen in advanced breast cancer are around 30 to 35%, increasing with patient selection for oestrogen receptor positivity. Tamoxifen must be regarded as first-line endocrine treatment in postmenopausal women, and may represent an alternative to first-line ovarian ablation in premenopausal women. An emergent role in primary therapy of elderly and frail patients with operable disease is apparent. Tamoxifen is also of benefit following surgery in male breast cancer, and may have a role as first-line endocrine treatment. Tamoxifen also has a potential role in other hormone-sensitive malignancies such as pancreatic carcinoma, and in treatment of benign breast disease. Finally, tamoxifen has a place in treatment of male and female infertility. because of adverse effects is rarely necessary. The most frequent adverse effects are related to the drug's anti-oestrogenic activity, and include hot flushes, nausea and/or vomiting, vaginal bleeding or discharge, and menstrual disturbances in premenopausal patients. Thus, tamoxifen continues to play a major role in management of female breast cancer in both early and advanced stages of disease, with a place also in treatment of male breast cancer and of infertility.
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PMID:Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. 266 Nov 95

60 patients with severe mastalgia of more than 6 months' duration were randomly selected for treatment with either tamoxifen 20 mg daily or placebo for 3 months. As measured by linear analogue scoring, pain relief was achieved in 22/31 (71%) of those receiving tamoxifen and 11/29 (38%) of those taking placebo. Patients who did not respond to the first course of treatment were allocated to the alternative treatment for 3 months. Pain control was achieved in 8/12 (75%) of those receiving tamoxifen and 2/6 (33%) of those receiving placebo. The commonest side-effects were hot flushes (27% of patients receiving tamoxifen and 11% of those receiving placebo) and vaginal discharge (17% tamoxifen, 7% placebo). Side-effects caused 6 patients in each group to discontinue treatment. Tamoxifen is of value in the management of severe cyclical and non-cyclical mastalgia, and relief can be achieved without undue side-effects in the majority of patients.
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PMID:Double-blind controlled trial of tamoxifen therapy for mastalgia. 286 62

Clinical results of tamoxifen ('Nolvadex'-ICI) monotherapy in 44 premenopausal women with advanced breast cancer have been reviewed. Objective tumor regression was achieved in 12 (27%) patients and a further 10 (22%) were classified as 'stabilized'. Median duration of response was 12.7 months at the time of analysis. Greatest benefits occurred in soft tissue dominant and receptor-positive tumors, but there was no correlation between tumor response and other clinical manifestations of estrogen deprivation (e.g. menstrual disturbance, hot flushes). The benefits of conventional doses of tamoxifen do not therefore appear to be influenced by menopausal status and compare favorably to achievements reported after surgical oophorectomy.
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PMID:Tamoxifen (Nolvadex) for premenopausal patients with advanced breast cancer. 636 11

Tamoxifen is an estrogen antagonist/agonist often associated with antiestrogenic effects such as hot flushes and vaginal dryness in premenopausal women. Estrogenic side-effects, such as thromboembolic phenomena and endometrial proliferation has been reported in postmenopausal women. Paradoxically, tamoxifen has also been shown to be capable of increasing estrogen levels in premenopausal women. Since tamoxifen is being used more frequently in this group of women, potential adverse effects are only now being recognized. Two cases of premenopausal women who developed symptomatic endometriomas while on tamoxifen for breast cancer, are reported. Stimulation of endometriosis should be considered when pain and an ovarian mass develops in a woman on tamoxifen. The unique effects of tamoxifen in premenopausal women may contribute to this even in the presence of regular ovulation.
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PMID:Endometriosis and tamoxifen therapy. 791 61

Tamoxifen is a nonsteroidal anti-estrogen frequently used in breast cancer therapy. Side effects to tamoxifen are uncommon (2%) but should be recognized and detected early by careful follow-up. Tamoxifen adjuvant therapy is absolutely indicated in postmenopausal breast cancer with estrogen-receptor--positive nodes. Recently, this indication has been extended to negative-node postmenopausal breast cancer. Mild acute side effects are the most frequent: hot flushes, menstrual irregularity, nausea, headache, vertigo, minimal modifications in blood cell counts. However, more serious accidents can occur. Increased risk of thromboembolism is linked to a fall in the level of antithrombin III. Ocular toxicity can occur. If such ocular lesions are diagnosed early enough, they can be cured by promptly withdrawing treatment. For patients given tamoxifen, there appears to be a small increase in risk of endometrial carcinoma, especially if the daily dose is > 30 mg. This over-risk requires adequate detection based on sufficient knowledge of the usual tamoxifen-related modifications in the endometrium. Physicians should also be aware of two favorable effects. Tamoxifen therapy leads to decreased cardiovascular morbidity and mortality in postmenopausal women and is associated with a significant increase in lumbar bone density. Risk of interaction with oral anticoagulants has been reported. We discuss here practical steps in the follow-up of women treated with tamoxifen.
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PMID:[Surveillance of patients treated with tamoxifen]. 868 11

The present studies evaluated the effect of estrogens and the selective estrogen receptor modulator (SERM) tamoxifen and raloxifene in a rat model for hot flush. In this model, ovariectomized rats were treated for 8 or 9 days either sc or po. Rats were dependent to morphine by implanting a morphine pellet (75 mg each) sc on days 3 and 5 of treatment. On the last day of treatment, a thermistor, connected to a data acquisition system, was placed on the tail of each animal and morphine addiction was withdrawn by naloxone injection (1.0 mg/kg, sc). Temperature measurements were taken for 1 h under ketamine (80 mg/kg, im) anesthesia. In general, vehicle treated rats showed a 5-6 degrees C elevation of their tail skin temperature with the peak occurring about 15 min after naloxone injection. 17 alpha-Ethinyl estradiol (EE) was evaluated both sc and po using a broad range of doses. The IC50 for inhibition of tail skin temperature rise was approximately 0.1 mg/kg, sc and 0.2 mg/kg, po. 17 beta-Estradiol and 17 alpha-estradiol were also active in this model whereas non-estrogenic steroids were inactive. Raloxifene and tamoxifen were tested for estrogen agonist and antagonist activity administered sc and po. Raloxifene did not demonstrate reproducible estrogen agonist activity at doses up to 10 mg/kg, whereas it demonstrated significant antagonistic activity at the 10 mg/kg dose regardless of the route of administration. Tamoxifen exhibited significant estrogen agonist activity at all doses tested (0.1-10.0 mg/kg) and was a significant antagonist of EE at the 1.0 mg/kg dose. Our results demonstrate the potential utility of this model to evaluate and discriminate among classes of compounds with varying degrees of estrogen agonist and antagonist activity.
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PMID:The effect of estrogens and antiestrogens in a rat model for hot flush. 988 31

Estrogens are known as potent mammary mitogen substances and are the major stimulus for the growth of hormone-dependent tumors and clearly implicated in the pathogenesis of breast cancer. Therefore it is a general belief that hormone replacement therapy (HRT) after breast cancer will increase the risk of developing recurrences, though there are no clear data available to support this suggestion. No prospective study with a large number of patients and a long treatment period was performed concerning this issue. On the other hand it may not be justifiable to withhold hormone replacement therapy from low-risk patients after menopause, knowing the benefits of this therapy concerning osteoporosis and cardiovascular advantages. Nevertheless, until appropriate clinical trials help to resolve this problem, non hormonal alternatives constitute the standard of care. One possible approach is to treat menopausal women who have had breast cancer symptomatically and avoid ERT unless absolutely necessary. The risk of cardiovascular diseases can be reduced with lifestyle. Tamoxifen has a beneficial effect on serum lipids and the intake for 5 years leads to a 50% reduction in the incidence of fatal myocardial infarction and a decrease in morbidity associated with ischaemic heart disease. Low doses of progestogen is effective for menopausal hot flushes. Tibolone reduces vasomotoric symptoms such as hot flushes and offers benefit on osteoporosis and has shown a significant reduction in high-density lipoprotein cholesterol. Whether replacing of estrogens is safe for patients after breast cancer remains uncertain. There is a need for a large controlled clinical trial to evaluate the safety and advantages of long time estrogen replacement in women treated for breast cancer.
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PMID:Estrogen replacement therapy in women with a history of breast cancer. 1046 73


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