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)

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
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PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89

Efficacy and safety of NK 622 (toremifene citrate) were compared with tamoxifen (TAM) by a double blind test in patients with advanced or recurrent breast cancer. NK 622 and TAM were given orally for 12 weeks or more at daily doses of 40 and 20 mg/body, respectively. Eligible cases in NK622 and TAM groups were both 57 patients. No significant difference was observed in patient characteristics between either group. Response rates were 26.3% (8 CR and 7 PR, 15/57) in the NK 622 group and 28.1% (3 CR and 13 PR, 16/57) in the TAM group. Median values of duration to onset of CR were 91 days in the NK 622 group and 169 days in the TAM group. The duration was significantly shorter with the NK 622 group. Median duration of efficacy in CR and PR cases was 155 days in the NK 622 group and 154.5 days in the TAM group. Adverse effects were encountered in 7 patients (12.3%) of each of the 2 groups. The side effects were fatigue, hot flush, WBC decrease, abnormal values in liver function tests, etc. in the NK 622 group and anorexia, nausea, eruption, feeling of warmth, sweating, dry mouth, dizziness, abnormal values in liver function tests, etc. in the TAM group. Administration was discontinued in one patient with eruption and another patient with abnormal values of liver function tests in the TAM group, while there was no such case in the NK 622 group. Including the discontinued cases, the side effects were moderate and reversible in both groups. The patients in whom a drug was determined as useful or more numbered 24/57 (42.1%) in the NK 622 group and 23/57 (40.4%) in the TAM group. There was not significant difference between the 2 groups in the above results except the duration to onset of CR. From these results, NK 622 is expected to show comparable efficacy, safety, and usefulness in patients undergoing TAM treatment for advanced or recurrent breast cancer.
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PMID:[Clinical evaluation of NK 622 (toremifene citrate) in advanced or recurrent breast cancer--a comparative study by a double blind method with tamoxifen]. 843 63

This study examines the symptoms after a natural menopause recalled by women aged 50-89 years. We determined the frequency and clustering of symptoms, the effect of age on symptoms, and the relation of symptoms to the use of estrogen therapy in a cross-sectional, community-based study of 589 Caucasian, middle- to upper-middle-class women from Rancho Bernardo, California. At the time of menopause, 55% of the women reported that they felt life was getting better and 57% were more cheerful. The most frequently recalled symptoms were hot flushes (74%), propensity to weight gain (45%), night sweats (35%), tiredness (32%), and insomnia (28%). Irritability was reported by one-fourth, depression by one-fifth. Nearly 11% reported anxiety about looking older. The recalled prevalence of hot flushes, irritability, weepiness and tiredness did not vary by current age, but younger women were significantly more likely than older women to have experienced night sweats, visible flushes, depression, anxiety about looking older and insomnia. Principal components factor analysis yielded four main independent factors: psychological symptoms (21% of the variance), vasomotor symptoms (14%), positive feelings (11%), and negative self-image (8%). The four symptom groupings suggest different causal mechanisms. Forty-two percent reported past, and 27% reported current use of estrogen therapy. Both past and current hormone users were significantly more likely to report menopause symptoms than non-users. Estrogen use was not associated with positive feelings or self-image at the time of menopause. Although three-quarters experienced symptoms, the majority of women reported positive feelings about menopause.
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PMID:A community-based study of menopause symptoms and estrogen replacement in older women. 853 87

Clinical evaluation in oncology has typically focused on outcome indicators, while less attention has been paid to how treatment affects quality of life (QOL) of the patient. In this article some general aspects of quality of life are discussed, a short review of published data on QOL in patients with prostate cancer is given and results of a QOL study executed by the authors on patients with lymph node positive prostatic cancer are presented. The purpose of the study was to examine the impact of immediate or delayed treatment (after objective progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of life parameters. To this end an extended questionnaire was constructed. Fifty-five patients participated. Assessment was performed twice, in 1994 and 1995. The comparison between patients with and patients without treatment showed in 1994 as well as in 1995 significant differences for hormonal treatment side effects such as sexual functioning and hot flushes, all of which were experienced more frequently by treated patients. In 1994 the treated patients experienced more psychological distress while in 1995 they showed worse physical function, less energy and more fatigue when compared to patients under surveillance. The premise that active treatment would improve the psychological quality of life was not sustained. In addition global health status and quality of life were identified as independent factors for progression in untreated patients with lymph node positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA) in hormonally treated patients not only indicated hormonal escape but also a decrease in QOL.
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PMID:Quality of life in patients with prostatic carcinoma: a review and results of a study in N+ disease. Prostate-specific antigen as predictor of quality of life. 914 92

The clinical examinations covered 1710 women. The investigations were performed on 199 women with symptoms of menopause, who were selected and divided into two groups. The first control group (I) included 80 women employed in the Industrial Clothing Factory "Dana" in Szczecin, without contact with carbon disulphide. The second study group (II) comprised 119 women employed in the Synthetic Fibres Factory "Chemitex-Wiskord" and exposed chronically to carbon disulphide in concentration of 9.36-23.4 mg/m3. The microclimate conditions of the production halls in both groups were similar (Tab. 1). Menopause was present in 16.59% of women in the population chronically exposed to carbon disulphide, as compared with 8.05% in the normal population. Mean age at menopause in women of the first group was 48.1 years and 43.9 years in the second group. In the studied group of menopausal women retrospective estimation of menopausal and gestational cycles shows statistically significant increase in abortion and disorders of menstrual cycles (p < 0.001) (Tab. 2). The women chronically exposed to CS2 had significantly more frequently headaches, weight gain and loss of libido (p < 0.001). In the normal group fatigue, palpitations and hot flushes were found significantly more often (p < 0.001) (Tab. 4). The serum concentrations of estrone (p < 0.01), estradiol, progesterone, 17-hydroxyprogesterone were significantly decreased in women chronically exposed to CS2 (p < 0.001). No significant differences in the level of FSH or LH were noted between both groups (Tab. 3). The daily excretion of adrenaline and noradrenaline in urine concentrations of dopamine in plasma of women chronically exposed to CS2, was significantly lower (p < 0.001), but the serum concentrations of serotonin (Tab. 5), testosterone, dehydroepiandrosterone sulphate (DHAS) and prolactin in plasma were significantly higher (p < 0.001). No difference concerning the level in serum of dehydroepiandrosterone and beta-endorfine was found (Tab. 6). Significant negative linear correlations between serotonin and FSH (r = -0.45; p < 0.001), serotonin and daily excretion of adrenaline (r = -0.43; p < 0.01) or noradrenaline (r = -0.58; p < 0.001) were disclosed in the exposed group. In this group a positive correlation was noted between the concentration of serotonin and prolactin (r = 0.45; p < 0.001).
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PMID:[The effect of carbon disulphide on menopause, concentration of monoamines, gonadotropins, estrogens and androgens in women]. 947 21

Menopause and the accompanying reduction in estrogen production may cause a number of symptoms in women which include hot flushes, sweating, mood and sleep disturbances, fatigue and urogenital dysfunction. The effectiveness of estrogen-based hormone replacement therapy (HRT) in ameliorating these symptoms, and in preventing long term sequelae such as osteoporosis, is well established. Comparative trials indicate that oral conjugated estrogens 0.625mg, oral ethinyl estradiol 0.02mg and transdermal estradiol 0.05mg have equivalent efficacy in relief of mild to moderate menopausal symptoms and prevention of bone mineral loss. Concomitant progestogen therapy is usually prescribed for women with intact uteri to protect against endometrial hyperplasia and carcinoma. The addition of progestogen maintains and may even enhance the bone-conserving effects of estrogen, and continuous regimens appear to reduce the incidence of irregular menses. Adverse reactions are predominantly local skin irritation with transdermal preparations (14% of patients) and systemic effects common to most forms of HRT including breast tenderness, flushing, headache and irregular bleeding, occurring in less than or equal to 2% of patients. Data concerning the effect of HRT on quality of life are limited, but most analyses have assigned utility values of 0.99 for mild and 0.95 for severe menopausal symptoms. However, recent clinical data suggest that these utility values may underestimate the impact of menopausal symptoms on quality of life. The cost benefit and cost effectiveness of HRT in the treatment of menopausal symptoms have not been fully researched, although preliminary results suggest that conjugated estrogens and transdermal estradiol compare well with alternative therapies such as veralipride and Chinese medicines. A Swedish study using a prevalence-based approach estimated that estriol treatment in all women with urinary incontinence aged greater than or equal to 65 years resulted in monetary savings compared with treating 20% of women. Cost-utility data indicated that the change in quality-adjusted life years (QALYs) with HRT was always positive, but the degree of change was determined by the baseline assumptions. Estimated changes in QALYs with HRT ranged from 0.006 for 5 years of treatment with unopposed estrogen in women with intact uteri, to 0.5 for 10 years of the same treatment in women with severe menopausal symptoms following hysterectomy. Compliance with HRT is suboptimal as 5 to 50% of women withdraw from therapy, thereby increasing costs per year of life saved.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. 1014 33

Exemestane is a steroidal agent which causes inactivation of the aromatase enzyme by binding irreversibly to the substrate binding site. Oral exemestane 25 mg/day inactivates peripheral aromatase activity (approximately 98% inactivation) and reduces basal plasma estrone, estradiol and estrone sulphate levels by 85 to 95% in postmenopausal women with advanced breast cancer. Phase II trials indicate that oral exemestane 25 mg/day is an effective second- or third-line agent in the treatment of postmenopausal women with advanced breast cancer (achieving an objective response in up to 28 and 26% of patients, respectively). Results from a phase III trial indicate that exemestane achieves a similar objective response rate to megestrol as a second-line therapy; however, exemestane achieved a significantly longer duration of overall success, time to disease progression and survival time. Exemestane is at least as well tolerated as megestrol, but is associated with significantly fewer bodyweight changes, mainly bodyweight gain (> or = 10%). Other common adverse events are hot flushes, nausea and fatigue.
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PMID:Exemestane. 1055 37

Menopause is defined as the final menstruation, directly preceding the permanent cessation of ovarian follicular function. The transition from the reproductive to the non-reproductive phase of life can take many years, frequently characterised by perimenopausal cycle disorders, vasomotor symptoms (hot flushes and night sweats) and urogenital complaints (vaginal dryness, micturition complaints). In addition to these typical climacteric symptoms other, more atypical symptoms can be present, such as tiredness, irritability and mood swings. Topical and systemic oral and transdermal HRTs are generally very effective as symptomatic treatment, but other non-hormonal options can also be considered.
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PMID:Menopause, HRT and menopausal symptoms. 1069 56

Third-generation aromatase inhibitors are able to reduce circulating plasma estrogen concentrations in postmenopausal women to below detectable limits and significantly inhibit aromatase, the enzyme responsible for estrogen synthesis, in normal breast tissue and breast tumors. Their role in the treatment of advanced breast cancer is well established and their use in adjuvant therapy is currently being explored. On the basis of these trials, evaluation of these inhibitors in the prevention of breast cancer may be appropriate. Aromatase inhibitors have non-specific toxic side effects including (but not limited to): asthenia, headache, nausea, peripheral edema, fatigue, vomiting and dyspepsia. In addition, certain endocrinological side effects in postmenopausal women are notable, namely hot flushes and vaginal dryness. In advanced breast cancer, these side effects result in treatment withdrawal in few (<4%) women. Of concern, however, are the potential long-term endocrinological side effects in women receiving treatment as first-line adjuvant therapy or in sequence or combination with tamoxifen or other selective estrogen receptor modulators (SERMs). Current studies of adjuvant treatments for breast cancer in healthy women are carefully evaluating, in addition to general toxicities, the effects on bone, lipid metabolism, cardiovascular risk, quality of life and menopausal symptoms. Careful evaluation of all-cause morbidity and mortality is necessary to plan trials and justify long-term use of aromatase inhibitors in the treatment or prevention of breast cancer in healthy women.
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PMID:Risks versus benefits in the clinical application of aromatase inhibitors. 1073 Nov 26

Hot flashes are among the most commonly reported symptoms among women who have completed treatment for breast cancer. Relatively little is known, however, about hot flashes among women while they are undergoing breast cancer treatment. The present study investigated the prevalence and severity of hot flashes of women during chemotherapy and radiotherapy for breast cancer. We also sought to identify the medical, demographic, and treatment correlates of hot flashes during treatment and to document the impact of hot flashes on quality of life. Seventy postmenopausal women with breast cancer completed a self-report questionnaire packet during chemotherapy and radiotherapy. Forty percent (n = 28) reported hot flashes during the week prior to assessment. Of the 28 women endorsing hot flashes, 25% (n = 7) rated them as severe, 39% (n = 11) rated them as moderate, and 36% (n = 10) rated them as mild. Women with hot flashes were significantly (p < 0.05) younger and reported significantly (p < 0.001) more fatigue, poorer sleep quality, and poorer physical health compared to women without hot flashes. Multivariate analyses revealed that, even after controlling for relevant medical, demographic, and treatment variables, the prevalence of hot flashes significantly (p < 0.05) predicted poorer sleep quality, more fatigue, and worse physical health. The results indicate that hot flashes are experienced by a sizable percentage of postmenopausal breast cancer patients as they undergo treatment. Hot flashes during cancer treatment appear to have a negative impact upon patient quality of life that may be due, in part, to fatigue and interference with sleep. Future research should seek to evaluate interventions to relieve hot flashes during breast cancer treatment as a means of improving patient quality of life.
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PMID:Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer. 1090 24


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