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)

Fourteen patients with advanced ovarian cancer who failed chemotherapy received a long-acting LHRH agonist. All the patients had been previously operated on and all had received at least one regimen of chemotherapy. Duration of decapeptyl administration was between 1 month and 28 weeks. There were no complete or partial responses. Eight patients (57%) had disease stabilization with a median progression-free interval of 14 weeks (range 4-28 weeks). All other patients developed a clear progressive cancer after the first injection of LHRH agonist. Three of these patients are still alive and receiving other forms of chemotherapy (median follow-up after the end of LHRH treatment was 11.5 months). The regimen was well tolerated with only mild toxicity observed (hot flushes in 2 patients). Although D-Trp-6-LHRH (Decapeptyl) was well tolerated, it had insignificant activity in treating patients with epithelial cancer that was resistant or relapsed after first-line platinum-based chemotherapy.
Cancer Invest 1995
PMID:A phase II trial of D-Trp-6-LHRH (decapeptyl) in pretreated patients with advanced epithelial ovarian cancer. 774 79

To determine the optimal daily dose of a new antiestrogen, droloxifene, for the treatment of advanced breast cancer, we have conducted a multicenter, randomized, double blind trial. Postmenopausal women with advanced breast cancer, who could not benefit from loco regional therapy, with positive or unknown estrogen or progesterone receptors were entered in this study. Droloxifene was administered in a double blind randomized design, with daily dose of either 20 (group I), 40 (group II) or 100 mg (group III). None of the patients had received previous systemic antitumor therapy, with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Patients with at least one measurable tumoral lesion were entered into the trial. Three hundred and sixty nine patients have been enrolled, 234 are fully evaluable for efficacy. Objective response rate (CR + PR) is 31.1, 44.6 and 41.9% for the groups I, II and III respectively (P = NS). Time to response has been short: in the three groups, 50% of the responses have been observed within the 2 first months of treatment. Time to disease progression is 6, 8.3 and 6 months respectively for the 20, 40 and 100 mg/day treatment group. Side effects have been moderate and not dose related. Hot flushes and gastro intestinal disorders have been observed most often. This promising new drug deserves further study and randomized comparison versus tamoxifen.
Bull Cancer 1993 Jul
PMID:[Treatment of advanced breast cancer in postmenopausal women with droloxifene: results of a double-blind phase II trial for dose determination]. 820 43

Estrogen replacement therapy (ERT) is very effective in relieving many menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and psychological disturbances. Moreover, it is effective in the prevention of postmenopausal osteoporosis and has a favourable effect on some risk factors for cardiovascular disease in the long term, via several mechanisms including mediating effects on the lipid profile. Most of these beneficial effects are maintained with transdermal estradiol therapy, involving the use of a cutaneous delivery system attached to the skin which delivers a controlled rate of estradiol over a period of up to 4 days. However, the clear demonstration of a favourable effect on some risk factors for cardiovascular disease remains to be established. Transdermal administration of estradiol appears to be at least as effective as oral conjugated estrogen therapy on most of the end-points which have been evaluated, but allows a lower dose to be used, avoiding some of the metabolic adverse effects experienced with oral treatment. Endocrinological adverse effects, such as breast tenderness, breakthrough bleeding and fluid retention, are similar in both treatments, and can be minimised by dose adjustments in most cases. The most common adverse effects related to transdermal therapy are local skin reactions at the site of application. These are usually mild and transient in nature, and can be overcome by changing the site of application. Serious risks of transdermal therapy appear to be the same as those for other forms of ERT, namely an increased risk of endometrial hyperplasia and cancer with estrogen therapy alone. However, combination therapy involving the sequential administration of a progestogen has been shown to substantially reduce the risk of endometrial proliferation. The potential increased risk of breast cancer has been controversial and appears to be minimal with ERT. The role of progestogens on breast cancer risk remains controversial, but the data to date do not indicate any significant change in risk when progestogens are added to ERT.
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PMID:A risk-benefit appraisal of transdermal estradiol therapy. 828 Apr 4

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

Improvement of quality of life (QoL) has become a major endpoint in clinical trials of patients with prostate cancer. However, there still exist considerable methodological problems regarding the development of optimal instruments and methods for presenting the results. Within the European Organisation for the Research and Treatment of Cancer (EORTC) a core questionnaire is generally used for QoL evaluation, combined with a treatment- and disease-specific module. So far, no official EORTC prostate cancer module has been developed. Previous and ongoing trials in prostate cancer have addressed the following issues: for localised prostate cancer, micturition and sexuality, and for metastatic prostate cancer, bone pain, micturition, sexuality, vitality, hot flushes and gynaecomastia. The future challenge is to incorporate QoL results into the overall evaluation of treatment in combination with survival results and economical considerations.
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PMID:Quality of life in prostate cancer: what are the issues and how are they measured? 871 74

Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal dryness in postmenopausal women and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role in the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.
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PMID:Phyto-oestrogens and Western diseases. 918 25

The chemotherapy side-effects are insufficiently documented while they strongly condition patients' quality of life. The aim of the study was to assess by means of a self-administered questionnaire the somatic symptoms experienced by breast cancer patients during their NCF (mitoxantrone + cyclophosphamide + 5-fluorouracil) chemotherapy and to demonstrate the interest of this self-report by comparing the frequency of side-effects assessed by the patients to that noted by the physicians in medical records. The study was carried out among 44 patients receiving their chemotherapy + radiotherapy at the Paoli-Calmettes Institute (marseille) between July 1994 and May 1995. The questionnaire comprized of 17 symptoms evaluated in terms of frequency, duration/severity and distress. The most frequent symptoms are: hair loss and nausea (75%), hot flush (57%), lack of appetite and headache (46%) associated with distress in 67 to 100% of cases. Their frequency was underestimated by the physicians in medical records. This study showed a large discordance patient-physician in the assessment of chemotherapy side-effects. The type of tool presented in this study could complement the usual scales of toxicity that do not provide an estimation of true patients' experience.
Bull Cancer 1997 Mar
PMID:[Adjuvant chemotherapy with mitoxantrone, cyclophosphamide and 5-fluorouracil in breast neoplasms: therapeutic life]. 920 68

The aim of the study was to compare efficacy and tolerability of the new aromatase inhibitor formestane (Lentaron) with megestrol acetate (Megestat) (MGA) in postmenopausal patients with advanced breast cancer. 179 patients were randomised to receive either 250 mg formestane intramuscularly biweekly or MGA 160 mg orally daily. 51% of the patients had received tamoxifen as adjuvant treatment; 73% of the patients had positive and 16% unknown oestrogen receptor values. The response rate was 17% in both treatment arms (95% confidence interval 10-26% for formestane and 10-27% for MGA). Disease stabilisation > or = 6 months was seen in 25% of the formestane and 22% of the MGA patients. Time to treatment failure was 120 days in the formestane arm and 111 days in the MGA arm. There was no significant difference between the treatments with regard to response rate and time to treatment failure. Overall toxicity was similar in both arms, but weight gain > 3 kg (P = 0.081) and severe cardiovascular toxicity (P = 0.044) were more frequently observed with MGA, e.g. deep vein thrombosis 0/90 formestane versus 5/81 MGA cases (P = 0.022). Formestane was associated with worsening of hot flushes/sleeping problems (P = 0.051) and mild leucopenia (P = 0.004). In our study, formestane and MGA showed similar antineoplastic activity as second-line hormonal treatment for advanced breast cancer. Both drugs have a specific toxicity profile. MGA was associated with significantly more severe cardiovascular toxicity and weight increase than formestane.
Eur J Cancer 1997 Jun
PMID:Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK) 937 2

Because side-effects of chemotherapy may be more diverse and patients' reactions more individualistic than tends to be acknowledged by clinicians, a survey was carried out among 50 breast cancer outpatients to document self-reported physical symptoms experienced during NCF (mitoxantrone + cyclophosphamide + 5-fluorouracil) adjuvant chemotherapy and to compare them with the clinicians' estimation in medical records. The questionnaire evaluated the prevalence, duration/severity and distress level of 17 symptoms. Symptom prevalence, assessed in 231 cycles, was high even for symptoms that do not usually focus clinicians' attention. Of these, hot flushes, stomach pain and muscular and articular pains lasted 1 week or more for nearly half of the cycles. Hot flushes, vomiting and stomach pain were the most distressing symptoms. The mean number of symptoms per cycle is significantly correlated with the global quality-of-life score. Concordance between patients' self-assessment and clinical reports, measured in 180 cycles, is moderately correct for vomiting and sore mouth and inadequate for the remaining symptoms even for hair loss (notified in 27% of cycles by clinicians vs 80% by patients) and nausea (38% vs 73%). A better understanding by physicians of cancer patients' problems is necessary to improve quality of care.
Br J Cancer 1997
PMID:Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care. 941 55

In a European multicentre phase II study, 80 postmenopausal patients (pts) with advanced breast cancer progressing on aminoglutethimide (AG) at daily doses of > or = 500 mg were enrolled. Seventy-eight received exemestane (200 mg daily orally), including 33 pts resistant to prior AG, 39 pts who had progressed after an initial response to AG, and 6 pts whose response to AG was either unavailable or not evaluable. Three pts were pretreated with AG only, 69 with tamoxifen and AG, and 6 with tamoxifen, AG and other hormone therapies; 55% had also previously received chemotherapy. The predominant site of disease was visceral in 34 cases, bone in 27 and soft tissue in 17. Based on Peer Review assessment, the overall objective response rate (CRs plus PRs) was 26% (12% in pts resistant to AG and 33% in AG-responsive pts). Disease stabilisation > or = 24 weeks was achieved in an additional 13% of patients (15% of those resistant to AG and 13% of those AG-responsive), resulting in an overall success rate of 39% (28-50, 95% confidence interval). The median duration of objective response, overall success and median TTP were 59, 48 and 21 weeks, respectively. Toxicities were usually mild to moderate in severity, with hot flushes (21%), nausea (19%), dizziness (12%), weakness (12%), increased sweating (12%), androgenic symptoms (10%) and peripheral oedema (9%) as the most common side-effects. Only 2 pts (3%) discontinued treatment due to adverse events. These results are very promising considering that exemestane was administered as third- or fourth-line hormonal treatment in most cases and confirm previous observations about the lack of cross-resistance when steroidal aromatase inhibitors are sequenced with the non-steroidal aromatase inhibitor AG.
Eur J Cancer 1997 Oct
PMID:Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase II multicentre multinational study. Exemestane Study Group. 947 Aug 30


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