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 One patient was withdrawn from the study because of a rash.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.
Cancer Chemother Pharmacol 1979
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.
Cancer Treat Rep 1976 Oct
PMID:Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. 79 26

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.
Cancer Chemother Pharmacol 1992
PMID:Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. 138 61

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.
Eur J Cancer 1992
PMID:Goserelin depot in the treatment of premenopausal advanced breast cancer. 138 37

A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N-demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622.
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PMID:[Phase I study of NK 622 (toremifene citrate)]. 146 43

An estimated 32,000 American men will die of prostate cancer this year. Local prostate cancer may be successfully treated by radical prostatectomy or radiotherapy. Advanced cases may necessitate the use of hormonal ablation with bilateral orchiectomy, an approach that is regarded as the gold standard of therapy but not always the preferred treatment of patients. Oestrogen therapy is an alternative but is associated with side effects, such as hot flushes and gynaecomastia, which frequently lead to treatment cessation. Luteinising hormone-releasing hormone (LHRH) analogues work by initially producing a surge of androgen, followed by a down-regulation in hormone production to effect a medical castration. Various groups have studied the effects of androgen blockade administered as monotherapy and as combination therapy (LHRH analogue plus antiandrogen). The National Cancer Institute intergroup protocol 0036, which is the largest cooperative study to date of patients with advanced prostatic cancer, showed that combination therapy with leuprolide and flutamide offered greater benefit in both time to disease progression and median survival while circumventing tumour flare and its associated symptoms. Thus, combination therapy for total androgen ablation may become the new treatment standard for advanced prostatic cancer, pending further studies in the efficacy and cost-effectiveness of all available treatments.
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PMID:Challenges in the management of prostate cancer. 146 76

We determined the ability of the multidrug resistance (MDR) reversal agent cyclosporin-A to increase anthracycline drug accumulation in colorectal tumour cells in vitro, using the technique of on-line flow cytometry. Data of four previously untreated patients showed that cyclosporin-A can increase intracellular net-uptake of daunorubicin. A phase II study was initiated in 24 colorectal cancer patients. They received cyclosporin-A at a dose of 3 mg kg-1 over 1 h as i.v. infusion, at 7 h and at 1 h preceding cytotoxic drug administration. At the end of the second cyclosporin-A administration epidoxorubicin 90 mg m-2 was administered as i.v. bolus. Cycles were repeated every 3 weeks. Median cyclosporin-A peak blood levels and levels at 18 h after cytotoxic drug administration appeared to be 6248 ng ml-1 and 1012 ng ml-1 respectively. Only one partial response was observed, despite these high cyclosporin-A levels. Cyclosporin-A did not cause major toxicity, only a 29% incidence of hot flushes was observed. Epidoxorubicin toxicities were as expected but the frequency of severe leucocytopenia was striking. This treatment schedule can not be considered active in colorectal cancer.
Br J Cancer 1991 Aug
PMID:A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance. 189 65

This study investigated the knowledge, views and experience of perimenopausal women in relation to hormone replacement therapy at the menopause. It was carried out in a semi-rural practice, using a postal questionnaire to which the response rate was 85%. The majority of women (90%) had heard of hormone replacement therapy, mainly from the media. However, only a quarter of the women had approached their general practitioner about the therapy, principally because they were experiencing definite symptoms. The majority of women believed hormone replacement therapy could benefit hot flushes and osteoporosis but only about 10% felt it could reduce the risk of a stroke or myocardial infarction. Over half of the women expressed one or more concerns about the therapy and the dominant anxiety was about cancer. These findings form the basis for improved care in terms of identifying needs and providing more appropriate information.
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PMID:Hormone replacement therapy--a survey of perimenopausal women in a community setting. 203 53

Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.
Br J Cancer 1990 Nov
PMID:A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients. 212 15

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.
Eur J Cancer 1990
PMID:Prevention of breast cancer with tamoxifen--an update on the Royal Marsden Hospital pilot programme. 214 54


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