Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
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PMID:Phase I study of toremifene in patients with advanced cancer. 183 8

Goserelin acetate implant is a newly approved depot formulation of a luteinizing hormone-releasing hormone (LHRH) agonist indicated for palliation of advanced prostate cancer. LHRH superagonists suppress gonadotropin release from the pituitary gland by causing down-regulation of receptors. The sustained-release dosage form contains goserelin acetate dispersed in a biodegradable copolymer matrix and is designed to release active drug over 28 days. Pharmacokinetic studies have demonstrated that, despite nonzero order release of goserelin from the matrix, goserelin acetate implant maintains serum concentrations of testosterone in the range normally found in castrated men (less than 2 nmol/L) throughout the recommended 28-day dosing interval. Response rates similar to those for orchiectomy and estrogen administration have been demonstrated. Combination therapy with either diethylstilbestrol or flutamide has produced favorable results, although the major advantage appears to be a reduction in the tumor flare seen during the first week of LHRH agonist therapy rather than an increase in response rate or survival. Adverse effects are similar to other LHRH agonists and include tumor flare during the first week of therapy, decreased libido, decreased erectile potency, hot flashes, and gynecomastia. In combination with flutamide, additional adverse effects include diarrhea, nausea, vomiting, and elevated hepatic aminotransferases, all of which can be attributed to flutamide administration. Local reactions are minimal; however, some patients require a local anesthetic before goserelin acetate implant injection. The recommended dose is 3.6 mg administered subcutaneously into the upper abdominal wall every 28 days. The average wholesale cost is approximately +320 per month. Formulary addition is recommended.
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PMID:Goserelin acetate implant: a depot luteinizing hormone-releasing hormone analog for advanced prostate cancer. 183 21

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
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PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.
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PMID:Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. 392 58

Progress in new drug developments is discussed in relation to newly registered drugs and drugs in the animal and/or clinical research stage. Of central nervous system drugs new neuroleptics, antidepressants, tranquilizers, psychotropics, antiparkinson and anticonvulsant agents are discussed in terms of chemical structure, pharmacokinetics and toxicity. Likewise for anti-infective drugs such as antibiotics, antifungal, and antiparasitic agents. New synthetic antiinflammatory glucocorticoids are being developed and tested for toxicity and clinical effect. Estrogen and gestagen research continues but few new substances with more effective action than currently-used compounds have been found. Initial clinical testing of Tibolon shows it to prevent postmenopausal osteolysis and hot flashes. ST-1435 is still being tested as an implantable contraceptive. It causes amenorrhea and reduces plasma estradiol and progesterone. No progress is seen in research on nonhormonal substances with contraceptive action, except for prostaglandins although no new derivatives with high tissue selectivity for uterine smooth muscle, nor early applicable abortifacients, have been found. Metenprost is being studied as a self-administered abortifacient: in one study 98% of completed abortions were seen with 30-40% adverse effects (nausea, vomiting, fever). DL204-IT and L-11,204 are triazoloisoindole and triazoloisoquinolone derivatives which have been tested in various dosages and dosage forms on animals in various pregnancy stages. Optimum contraceptive action occurs in the early blastocyst stage. The plant extracts Zoapatanol and Montanol show dose-dependent inhibition of implantation in animal studies but the contraceptive action mechanism is not known. Oxendolone shows an unmistakable antiandrogenic effect. Action mechanism is assumed to be inhibition of the 5 alpha-reduction of testosterone. It has a long plasma half-life in rats (3.6 days). It has been clinically tested in Japan (weekly intramuscular injection of 200-400 mg) in prostatic hypertrophy. Longterm studies are not yet available.
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PMID:[Progress in the area of drug development. 15]. 613 42

In a pilot study a combination of metoclopramide and dexamethasone was administered to 29 patients receiving emetogenic chemotherapy. Metoclopramide was given intravenously (IV) at a dose of 0.5 mg/kg one-half hour before the start of chemotherapy, and then given at the same dose orally two, five, and eight hours after chemotherapy. Dexamethasone was given at a dose of 10 mg IV immediately following the first dose of metoclopramide, then given at a dose of 8 mg orally six, 12, and 18 hours after chemotherapy. The chemotherapy regimens most commonly used were standard FAC, FAM, and BACOD regimens. Twenty-six of 29 patients received outpatient treatment. Complete protection against both nausea and vomiting was seen in 69% (20/29) patients; six others (21%) experienced mild nausea but no vomiting, resulting in 90% (26/29) of the patients having total emetic protection with combination metoclopramide and dexamethasone. Eighty-eight percent (15/17) of the patients with no prior chemotherapy had no nausea or vomiting, one (6%) had only mild nausea, and the remaining patient (6%) had one emesis. Forty-two percent (5/12) of the patients with prior chemotherapy had complete antinausea and emetic protection, five (42%) had nausea without vomiting, and the remaining two patients experienced one or two emesis. Side effects were minimal when present and included mild drowsiness (five patients), akathisia (three patients), diarrhea (one patient), and hot flashes (one patient). Combination metoclopramide and dexamethasone therapy can effectively prevent emesis in 94% of patients receiving potentially emetogenic chemotherapy and can prevent nausea and emesis in 88% of untreated patients. Studies defining the optimal dose and scheduling needed to maintain such antinausea and antiemetic protection are necessary.
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PMID:Combination metoclopramide and dexamethasone: an effective antiemetic regimen in outpatients receiving non-cisplatin chemotherapy. 647 Jul 55

Ten women ages 22 to 39 years were treated with a single injection of Delestrogen on day 19 of the menstrual cycle and increasing doses of Parlodel on days 19 to 23. This treatment resulted in a shortening of the luteal phase and a decrease in the production of progesterone and had no effect on serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), or prolactin levels. Side effects reported with this therapy included lethargy, dizziness, nausea, vomiting, hot flashes, depression, and nasal congestion. These preliminary clinical data suggest a combination of estrogen and bromocriptine regimen is luteolytic and may be useful as an interceptive abortifacient preparation in the human being.
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PMID:Evaluation of Delestrogen and Parlodel as a luteolytic agent in humans. 706 Jul 69

The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea was studied in a prospective, controlled, double-blind, cross-over study comprising 73 patients aged 13-39 with an average body weight of 56 kilos. The patients were randomized to receive either tolfenamic acid (200 mg t.i.d.) or mefenamic acid (500 mg t.i.d.) for 3 days, during 3 consecutive menstrual cycles each, in a sequential design A-B or B-A. At the beginning and at the end of each treatment period, 13 dysmenorrhoeic symptoms were evaluated on a visual analogue scale (lower back pain, interference with daily activities, nausea, vomiting, diarrhoea, headache, dizziness, fatigue, sweating, chills, hot flashes, depressant states, and mood swings). The data were analyzed by using two statistical models. The first one, for the 73 patients, by making paired comparisons regardless of treatment sequence. With respect to the initial values, the results showed that both drugs were statistically significant (P < 0.05) in reducing the intensity of the evaluated symptoms. When comparing both treatments, tolfenamic acid showed a significant difference as to interference with daily activities (P < 0.025) and hot flashes (P < 0.005). In the result analysis with the second model, the groups were divided according to the first assigned treatment and paired comparisons were made. It was observed that the group receiving tolfenamic acid in the last sequence reached a higher level of response and statistical significance was demonstrated in 8 of 13 evaluated symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea. 781 93

Toremifene (Fareston) is a triphenylethylene derivative structurally similar to tamoxifen (Nolvadex) that was selected for development based on its in vitro activity against breast cancer and its lesser uterotrophic effect than tamoxifen in rat models. In phase I and II studies conducted in several countries, toremifene was well tolerated over a wide range of doses (10 to 680 mg/d). The major side effects were hot flashes, nausea, and vomiting. Toremifene's excretion half-life is 5 days. It produces a modest decline in serum levels of luteinizing hormone, follicle-stimulating hormone, and antithrombin III, as well as an increase in sex hormone-binding globulin levels. In studies in which toremifene was used as first-line therapy in patients with estrogen receptor (ER)-positive or ER-unknown tumors, response rates to doses of 40 to 60 mg/day ranged from 30% to 54%. In two larger studies of patients who had proved refractory to tamoxifen therapy, toremifene produced an objective response rate of 4% to 5%. When patients with stable disease were added to those with objective responses, 27% to 28% of patients were considered to derive clinical benefit from toremifene. The dose range chosen for further study was 40 to 60 mg/d.
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PMID:Phase I and II studies of toremifene. 916 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.
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PMID:Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care. 941 55


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