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)

Retinoids have shown a tumor growth inhibition and a synergistic activity with hormonal manipulations in human breast cancer cell lines and rat mammary carcinoma. To investigate the potential usefulness of this synergistic activity in human breast cancer, 33 postmenopausal patients with advanced disease were treated with the combination of tamoxifen (10 mg p.o. three times a day) and retinyl acetate (300,000 IU p.o. daily). Out of 31 evaluable patients, 3 achieved complete response, 9 partial response (overall response rate: 38.5%, 95% confidence interval = 21%-56%) and 16 (52%) showed no change. The median duration of response was 11.5 months (range: 3-19+ months), while the 2-year overall survival rate for the entire group of patients was 63%. Toxicity was generally mild, hot flushes, nausea (and/or vomiting), headache and cutaneous itching being the most frequent side-effects. Only 1 patient discontinued treatment for severe toxicity. These preliminary results suggest that the combination of tamoxifen and high-dose retinyl acetate is a safe and effective regimen for breast cancer patients. However, the study design does not allow us to establish whether the very low rate of early disease progression we observed might be related to a possible synergistic effect between retinoids and antiestrogens or rather to the quite indolent disease of the patients who have been selected for entry into this trial.
J Cancer Res Clin Oncol 1990
PMID:Phase II study of tamoxifen and high-dose retinyl acetate in patients with advanced breast cancer. 222 42

Premenopausal breast cancer patients frequently develop amenorrhea during adjuvant chemotherapy. Despite psychic distress and severe weight loss are possible causes for secondary amenorrhea in cancer patients, it is in this case due to the gonadotoxicity of the cytostatic drugs. Alkylating agents, such as cyclophosphamide, damage ovaries directly, resulting in ovarian fibrosis, atretic follicles and decline in estrogen production. Elevated plasma levels of LH and FSH show adequate reaction of the hypothalamohypophyseal unit. There is no change in the androgen production of stromal cells as well as in the plasma levels of prolactin and adrenal androgen precursors. Ovarian damage goes along with hot flushes, loss of libido and dyspareunia. The onset of amenorrhea is age- and dose-related. Commonly the changes are irreversible. Estrogen replacement therapy promptly removes menopausal symptoms but is contra-indicated regarding the possible hormone-dependence of the tumor. In this case low dose medroxy-progesterone acetate is indicated.
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PMID:[Effects of adjuvant chemotherapy of breast cancer on gonadal function]. 223 81

This study was undertaken to determine whether intranasally administered buserelin, a gonadotrophin releasing hormone analog agonist, can be given with CAF to premenopausal women with advanced and/or metastatic breast cancer, and to assess toxicity and therapeutic effect. Of 24 women entered into the study 22 were evaluable; objective responses were documented in 18 patients (seven CR and 11 PR). The median time to treatment failure was 402 days. Buserelin, given with CAF, was well tolerated with the only additional side-effect being hot flushes. Amenorrhea occurred in 13/17 menstruating women and serum estradiol levels decreased to postmenopausal values in all patients.
Eur J Cancer Clin Oncol 1989 Apr
PMID:CAF and nasal buserelin in the treatment of premenopausal women with metastatic breast cancer. 249 19

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

Ten men with advanced breast cancer were evaluated for response to treatment with the luteinizing hormone-releasing hormone (LH-RH) analogue, buserelin, alone or in combination with the antiandrogen, flutamide. One of five patients receiving buserelin as a single agent had a partial remission lasting 12 months, and with the addition of flutamide, this lasted over 24 additional months. Three patients had stable disease with a median duration of 6 months (range, two to 14). One patient had progressive disease. Of five patients receiving the combination of buserelin and flutamide from the beginning of therapy, four patients had a partial remission with a median duration of over 15 months (range, over five to 16). One patient's disease remained stable for 12 months. Major side effects were hot flushes, loss of libido, and impotence. Buserelin initiates a castration-like endocrine response and has potential in the treatment of men with disseminated breast cancer when used either alone or in combination with flutamide.
Cancer 1988 Aug 01
PMID:Advanced male breast cancer treatment with the LH-RH analogue buserelin alone or in combination with the antiandrogen flutamide. 313 19

Symptoms due to estrogen deficiency begin in the perimenopausal years and progress as serum levels of this hormone decrease Vasomotor instability, manifested by hot flushes or night sweats, may persist for several months to a few years. Psychologic symptoms include anxiety, tension, depression, insomnia, palpitations, and headaches. Atrophy of the genital epithelium may result in senile vaginitis with symptoms of irritation, burning, pruritus, dyspareunia, and even vaginal bleeding. Even the lower urinary tract mucosa is dependent upon estrogen. Postmenopausal osteoporosis affects 25 to 50% of older women and increases the risk for vertebral, hip, and other fractures. Estrogen therapy for menopausal complaints has received adverse publicity because several reports have indicated that unopposed estrogens increase the risk of endometrial cancer. Added progestogen not only negates this risk but reduces the incidence of endometrial adenocarcinoma in estrogen-progestogen users to less than that observed in untreated women. Estrogen replacement therapy does not increase the risk of breast cancer; the incidence of this malignancy, however, was also less in the estrogen-progestogen users when compared with either the untreated women or from that expected from the national cancer surveys. In evaluating postmenopausal women for hormone replacement, the benefits of estrogen-progestogen therapy must be weighed against possible risks.
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PMID:The menopause. 351 23

A phase I study of benzisoquinolinedione (amonafide) was conducted in 30 patients with advanced solid tumors refractory to conventional therapy. The starting dose was 10 mg/m2/day X 5 days and the highest tolerated dose was 625 mg/m2/day X 5. The daily dose was mixed in 100 ml of normal saline and infused over 30-60 minutes. The dose-limiting toxicity was myelosuppression with nadirs of blood counts reached on Day 15 and recovery by Day 21-28. Other side effects included mild nausea and vomiting, mild phlebitis, skin rashes, and alopecia in some patients. A majority of the patients experienced dizziness, tinnitus, and hot flushes occurring predominantly at the higher dose levels. These were related to the rate of drug infusion and resolved on prolonging the infusion to 60 minutes. Pharmacokinetic studies of amonafide revealed a monoexponential plasma disappearance curve with a mean half-life of 3.5 +/- 1.9 hours. The recommended dose of amonafide for phase II studies in solid tumors is 400 mg/m2/day X 5 for good-risk and 300-320 mg/m2/day X 5 days for poor-risk patients with courses repeated at 21-28-day intervals.
Cancer Treat Rep 1987 Dec
PMID:Phase I clinical investigation of benzisoquinolinedione. 369 May 26

A phase I study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg-1 which was escalated up to 7 mg kg-1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg-1. In Schedule 2, the daily dose was started with 1.5 mg kg-1 which was escalated up to 8 mg kg-1 and given for 2-16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg-1 daily X 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg-1 of BHAC were administered the half-lives of the initial phase (t1/2 alpha) and the second phase (t1/2 beta) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin's disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.
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PMID:Phase I clinical and pharmacokinetic study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine. 370 7

Hormone-replacement therapy for postmenopausal women has associated benefits and risks. The advantages of the administration of estrogen to postmenopausal women include preventing or reversing the atrophic changes of the genitourinary system, slowing of facial aging, relieving hot flushes and psychological symptoms, preventing atherosclerotic heart disease and retarding the development of osteoporosis. The disadvantages of the administration of estrogen to postmenopausal women include rare but serious clinical sequelae associated with the ingestion of the synthetic estrogen when it is one component of the combination oral contraceptives, increased risk of cancer developing in the estrogen-dependent organs and uterine bleeding. The benefits of long-term cyclic estrogen-gestagen therapy in preventing osteoporosis far outweigh the risks.
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PMID:The menopause. 709 Mar 70

In western countries more than 30% of the female population are postmenopausal. Approximately 30% of postmenopausal women suffer from clinical symptoms of the climacteric such as vasomotor symptoms, associated with hot flushes, night sweat, insomnia and depressive mood. Sufficient hormonal replacement therapy (HRT) will abolish specific menopausal symptoms in over 90% of patients, unspecific symptoms such as headache respond to placebo and HRT equally well. The question of cancer risk related to HRT will be addressed in this review. In combination with progestins, estrogens are obviously protective regarding ovarian and endometrial cancer. The association between HRT and breast cancer risk is presently unclear. Epidemiological data available so far do not provide compelling evidence as to a cause and effect relationship between HRT and breast cancer risk. There seems to be an overall trend towards a slightly increased risk with increasing duration of HRT use. Guidelines for HRT use in women with a history of endometrial and breast cancer are provided in this article.
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PMID:Benefits and risks of hormone replacement therapy (HRT). 762 55


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