Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.
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PMID:Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer. 38 55

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.
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PMID:Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. 138 61

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.
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PMID:Aminoglutethimide in patients with metastatic breast cancer. 246 35

From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.
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PMID:Aminoglutethimide in advanced breast cancer. 286 33

The prolactin release inhibiting action of the dopamine receptor agonist metergoline was investigated in 16 patients with metastatic breast cancer associated with hyperprolactinemia. At a daily dose of 12 mg p.o. for 30 days, the drug was highly effective in lowering prolactin levels (day 0: 1076 +/- 171, day 29: 249 +/- 46 mU/l) in these patients. Starting treatment with 4 mg/day, the side effects of the treatment were mild, including dizziness and nausea.
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PMID:[Metergoline in hyperprolactinemic breast cancer: a phase II study]. 310 Oct 16

Eighty-seven consecutive patients with metastatic breast cancer were treated with aminoglutethimide plus hydrocortisone. All patients were postmenopausal and had progressive disease following prior chemotherapy and endocrine therapy. Eighty-five women were evaluable for drug response. One patient showed complete remission and 14 patients partial response, for an overall response rate of 17%. The median duration of response was 11+ months. The response rate was highest in the presence of soft tissue involvement (36%). The most common side effects were transient skin rash, lethargy, and dizziness. Two patients discontinued treatment because of cutaneous allergy. Aminoglutethimide can be considered a moderately active agent when utilized as second- or third-line hormonal therapy.
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PMID:Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments. 366 Apr 75

Thirty-eight metastatic breast cancer patients were treated with aminoglutethimide. All patients had progressive metastatic disease following initial response to Tamoxifen therapy. Thirty-two patients were evaluable for response, of these, two patients (6%) had complete remission, 13 patients (41%) had partial response, and six patients (19%) had stable disease. Eleven patients (34%) had progressive disease. The most common side effects were transient skin rash, lethargy or dizziness. Four patients' (11%) treatment was discontinued because of either skin rash or dizziness within the first two weeks of the study. These data show that aminoglutethimide is an effective agent following tamoxifen therapy.
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PMID:Treatment of advanced breast cancer with aminoglutethimide after therapy with tamoxifen. 618 Aug 20

This phase II, multicentre, open-label, clinical trial evaluated antitumoral efficacy, tolerability and endocrine effects following 25 mg of treatment with oral exemestane given daily to postmenopausal women with metastatic breast cancer. Eligibility criteria included oestrogen and/or progesterone positivity or a prior response to hormonal therapy if receptor status was unknown; prior failure to tamoxifen therapy; and progressive disease. Patients were divided into three strata: patients who did not respond to tamoxifen or progressed after disease stabilisation (SD) for less than 6 months (stratum 1); patients who, after an initial response or SD lasting at least 6 months, experienced disease progression whilst on tamoxifen (stratum 2); patients with recurrent metastatic disease during or within 12 months of discontinuing adjuvant tamoxifen (stratum 3). Of the 137 patients who received exemestane, 4 experienced a complete response (CR) and 28 a partial response (PR), for an overall response rate of 23%. Another 33 patients had SD for > or = 24 weeks, resulting in an overall success rate of 47%. The median time to objective response was 16.1 weeks (95% confidence interval (CI) 9.9-24.1). The median response duration was 69.4 weeks, the median duration of overall success 59.1 weeks, the median time to progression (TTP) 25.1 weeks and the median time to treatment failure (TTF) 24 weeks. Response to previous hormonal therapy had little effect on the results, except that there was a trend toward a higher overall success rate in patients who did not respond to previous hormonal therapy. After 8 weeks of therapy, serum levels of oestradiol (E2), oestrone (E1) and oestrone sulphate (E1S) were suppressed to 15.2%, 9.7% and 10.7% of baseline, respectively. The most common adverse events of drug-related or indeterminate cause were hot flushes (14%), dizziness (9%), nausea (8%) and increased sweating (5%). Exemestane had a favourable effect on performance status and tumour-related signs and symptoms, both of which improved or stabilised in approximately 67% and 68% of patients respectively. Exemestane is a unique therapy that is highly active and well tolerated as a new treatment for women with metastatic breast cancer.
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PMID:High activity and tolerability demonstrated for exemestane in postmenopausal women with metastatic breast cancer who had previously failed on tamoxifen treatment. 1088

Dural metastasis of metastatic breast cancer has become an increasingly diagnosed entity due to advanced radiological imaging. We present an autopsy case of a 51-year-old woman who presented with dizziness, had dural metastasis with subdural hematoma from a primary high-grade invasive ductal breast carcinoma. The pathogenesis of dural metastasis in our case was due to hematogenous dissemination while the subdural hematoma was due to destruction of vessels by tumor cells. The postmenopausal age and the high-grade histology of our case according to published literature signify a poor prognosis and would have meant an ante mortem median survival time of less than one year. Several studies have shown that treatment of intracranial metastatic cancer improves survival. Early recognition and diagnosis of symptoms of dural metastasis will alleviate the neurological complications of dural metastatic breast cancer. Our case report attempts to contribute to the understanding of dural metastasis in breast cancer and emphasize the importance of CNS surveillance in the treatment of a systemic primary cancer.
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PMID:Dural metastatic cancer from primary breast carcinoma. 2050 16

We included 58 premenopausal patients with metastatic breast cancer in an open study with leuprorelin acetate monthly depot. The overall response rate was 15/50 patients (30%). The median duration to tumour progression according to Kaplan-Meier analysis was 12 months. After leuprorelin acetate treatment permanent suppression of ovarian function was recorded with oestradiol levels below 30 pg/ml. The side effects were acceptable. The most common were: menopausal complaints, headache, dizziness and nausea. Changes of laboratory parameters were caused by cessation of ovarian function and progression of the underlying disease. Leuprorelin acetate is an effective drug for first line palliative treatment of premenopausal, metastatic breast cancer. The objective response rate is similar to other GnRH analogues and to reported data on surgical oophorectomy.
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PMID:Clinical efficacy of leuprorelin acetate monthly depot in premenopausal patients with metastatic breast cancer. 2159 Jan 27


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