Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-six women with breast cancer treated with adjuvant FAC (fluorouracil, doxorubicin and cyclophosphamide) entered a multicenter, randomized, double-blind, cross-over trial in which thiethylperazine (T) (6.5 mg p.o every 8 h x 3 days) plus methylprednisolone (MP) (250 mg i.v. x 2 doses) was compared with thiethylperazine plus placebo. Forty-four patients were evaluable for efficacy. T + MP was significantly better in reducing vomiting (p less than 0.01) and nausea (p less than 0.02). The complete protection rate against vomiting was 36% for T + MP compared to 18% for T + placebo, and the percentage of nausea grades 0 + 1 (none or slight) was 59% and 27% respectively. The patient preference after cross-over was strikingly in favor of T + MP (70% versus 13%) (p less than 0.001). The most important side-effects of T + MP were facial flushing (22%) and euphoria (27%). Other side-effects, such as dryness of the mouth and sedation, were common after both treatments. In conclusion, the study suggested that T + MP is superior to T alone in protecting from nausea and vomiting induced by FAC.
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PMID:The antiemetic efficacy of thiethylperazine and methylprednisolone versus thiethylperazine and placebo in breast cancer patients treated with adjuvant chemotherapy (fluorouracil, doxorubicin and cyclophosphamide). A randomized, double-blind, cross-over trial. 203 44

Fifty-three breast cancer patients receiving adjuvant chemotherapy entered a double-blind randomized trial of lorazepam 2.5 mg orally prior to chemotherapy and repeated after 12 hours (Arm A) versus placebo (Arm B) with methylprednisolone (MPN) 375 mg in 3 equal doses: 125 mg i.v. prior to chemotherapy and repeated i.m. 6 and 12 hours later. Adjuvant therapy with 5-fluorouracil 600 mg/m2, 4'-epi-doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 (FEC) day 1 was alternated every 21 days with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2 (CMF) day 1 for a total of 12 courses. The majority of patients experienced greater than or equal to 5 emetic episodes with FEC therapy (Arm A = 52%; Arm B = 55%). Mild and moderate nausea were reported by 60% and 68% of patients in Arms A and B, respectively. With CMF therapy complete control of emesis was observed in 33% (Arm A) and 35% (Arm B) of patients. The addition of lorazepam did not improve results either with FEC or CMF. Sedation was experienced by 86 to 92% of patients treated with lorazepam and amnesia was observed in 48-50% of cases. FEC therapy must be considered a highly emetic regimen and antiemetic therapy planned accordingly.
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PMID:Double-blind randomized trial of lorazepam versus placebo with methylprednisolone for control of emesis due to non-cisplatin containing chemotherapy. 209 Jul 73

Thirty-one postmenopausal women with advanced breast cancer have been treated with the nonsteroidal competitive aromatase inhibitor CGS 16949A at p.o. doses of 0.3, 1, and 2 mg twice a day. All patients were assessed for response. Five patients, all treated with 1 mg twice daily, had objective evidence of response (two complete responses and three partial responses); disease stabilized in 17 patients. Minor side effects were reported by ten patients. Two further patients treated with 2 mg twice a day experienced persistent nausea which improved after dose reduction, and one patient, treated with 0.3 mg twice daily, developed a vasculitic rash requiring discontinuation of CGS 16949A. Estradiol levels measured in 24 patients were significantly suppressed 2 wk after starting CGS 16949A treatment at all doses used. Treatment with 2 mg twice a day lowered estradiol levels to a mean of 29% of pretreatment values which was significantly lower than the corresponding figure of 57% for patients treated with 0.3 mg twice daily. Aldosterone levels were significantly lowered below pretreatment values by the 1- and 2-mg twice daily doses. No clinically apparent cases of adrenocortical insufficiency occurred, although small changes in serum electrolyte levels were noted. The results indicate that CGS 16949A is an effective aromatase inhibitor, requiring further evaluation in the treatment of advanced breast cancer. The optimal dose is likely to be 1 mg twice a day.
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PMID:Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. 213 67

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.
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PMID:Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group. 213 77

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.
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PMID:A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. 214 Aug 54

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.
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PMID:A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. 214 91

Fourteen postmenopausal women with estrogen-receptor positive advanced breast cancer and no prior cytostatic treatment received 20 mg toremifene daily as a single dose after a loading dose (120----60----60 mg) for the first 3 days. All were evaluable and had undergone at least 6 weeks' treatment. Results were: no complete remissions (CR), 3 partial remissions (PR), 8 no change (NC) and 3 cases of progressive disease (PD). Three patients had mild side effects: nausea, insomnia, sweating and arm pain.
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PMID:Treatment of advanced breast cancer with 20 mg toremifene, a phase II study. Preliminary communication. 214 39

The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy.
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PMID:Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. 182 40

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.
Breast Cancer Res Treat 1990 Aug
PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

The antitumor activity of the new triphenylethylene drug toremifene has been studied in advanced breast cancer of postmenopausal women as first line treatment at dose levels of 20, 60, and 240 mg, and as second line or later treatment at high dose levels of 200-240 mg. The response rates (complete + partial response) have been 21% with 20 mg (14 patients), 52% with 60 mg (93 patients in three separate trials), and 68% with 240 mg (38 patients) as first line treatment. After failure on previous therapy (hormonal or chemotherapy) the response rates have been about 10% with 200 mg of toremifene (71 patients in two different trials). In patients whose disease had previously responded to tamoxifen with at least stabilization, the response rate with toremifene has been 23%; but among unselected patients, including patients progressing during adjuvant tamoxifen, the response rate (CR + PR) with toremifene in tamoxifen failures has been 3%. If long lasting (more than 5 months) stabilization of the disease is also considered, a further 20% of previously treated patients have benefitted from toremifene. The treatment has been well tolerated at all dose levels. The most reported side effects have been hot flushes (8-19%) and nausea (8%). 0-6% of patients in different trials have interrupted the treatment because of side effects.
Breast Cancer Res Treat 1990 Aug
PMID:Phase II trials with toremifene in advanced breast cancer: a review. 214 83


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