Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 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

We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide.
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PMID:[Phase I study of FK 435]. 219 79

Twenty-six patients with metastatic breast cancer who had previously responded to one or more endocrine therapies participated in a clinical trial of the combination of trilostane and hydrocortisone for subsequent disease progression. Of these, one patient achieved complete remission (4%), and five had partial response (19%). The median time to progression from initiation of therapy for responding patients was six months (range: 4 - 32 + months). Major toxicities included nausea/vomiting (16 patients), facial flushing (14), abdominal cramping (11), and oral paresthesia (10). Therapy was discontinued in four patients (15%) because of drug intolerance. Fourteen patients who failed trilostane were treated with aminoglutethimide and hydrocortisone. Six patients showed objective response (PR + MR). These data show that trilostane and hydrocortisone in combination can produce an objective response in a significant fraction of patients and that the combination has a different spectrum of toxicity from aminoglutethimide/hydrocortisone. A small number of patients crossed over to aminoglutethimide showed a few objective responses, suggesting a partial lack of cross-resistance between the two antiadrenal drugs.
Breast Cancer Res Treat 1989 Mar
PMID:Trilostane with hydrocortisone in treatment of metastatic breast cancer. 265 3

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT3) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%-98% and 77%-93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect followed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.
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PMID:Control of emesis by intravenous granisetron in breast cancer patients treated with 5-FU, epirubicin and cyclophosphamide. 803 7

We gave miproxifene phosphate to six patients with recurrent breast cancer and to one patient with advanced breast cancer. This drug was orally administered at a daily dose of 20 mg in the morning, and serial blood samples were obtained just before the drug administration. Treatment was discontinued in 16 days in the patient with advanced breast cancer. Tumor response was 2 PR and 4 NC (3MR) with an efficacy rate of 29%. Adverse effects of grade 2, such as anorexia, nausea or vomiting and fatigue with grade 3 flushing and chilling were observed in the one patient with advanced breast cancer. This climacteric syndrome disappeared after cessation of administration. In one of the patients with recurrent breast cancer, a calf muscle cramp was observed. Steady plasma levels were observed in one week or two for miproxifene and in 2 to 8 weeks for desmethyl miproxifene, which were active metabolites of miproxifene phosphate. The half lives of these metabolites for disappearance were calculated in three patients. That of miproxifene was 27 to 36 hours and that of desmethyl miproxifene was 156 to 202 hours. Miproxifene phosphate is a promising drug for breast cancer, and the results of pharmacokinetics of active metabolites will suggest the time to obtain maximum efficacy and for it to disappear.
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PMID:[Steady state and disappearance of the metabolites of miproxifene phosphate in the treatment of breast cancer]. 972 50

Edrecolomab is a mouse-derived monoclonal IgG2a antibody. It recognises the human tumour-associated antigen CO17-1A which is expressed on the cell surface of a wide variety of tumours and normal epithelial tissue. Edrecolomab is thought to destroy tumour cells by activating an array of endogenous cytotoxic mechanisms, including antibody-dependent cell-mediated cytotoxicity and possibly antibody-dependent complement-mediated cytotoxicity. Edrecolomab may induce antitumour activity indirectly by inducing a host anti-idiotypic antibody response. Adjuvant therapy with edrecolomab (500 mg initial dose followed by four 100 mg infusions administered at 4-weekly intervals) significantly improved survival and reduced the tumour recurrence rate in patients with resected Dukes' stage C colorectal cancer and minimal residual disease. Data from several small clinical trials suggest that edrecolomab given as monotherapy or in combination with other antineoplastic agents has limited efficacy in the treatment of advanced colorectal or pancreatic tumours. However, results from a small phase I study in patients with advanced breast cancer were more promising. Edrecolomab was generally well tolerated in clinical trials. In a postmarketing surveillance study, the most common adverse events associated with edrecolomab were flushing/erythema and gastrointestinal symptoms including diarrhoea, abdominal pain and nausea and vomiting. Because edrecolomab is of murine origin, anaphylactic reactions have developed in some patients treated with the drug.
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PMID:Edrecolomab (monoclonal antibody 17-1A). 980 8

The purpose of the present study was to examine whether its is possible to successfully replace ondansetron (OND) with metoclopramide (MCP) in patients exposed to moderately emetogenic chemotherapy who did not experience severe nausea and vomiting while undergoing OND treatment during their first chemotherapy cycle. After switching to MCP, patients continued with this drug for three cycles, provided that they had adequate control of nausea and vomiting. Otherwise, they were switched back to OND. There were 76 patients, 60 women and 16 men, whose median age was 56 (mean 58) years. Karnofsky performance status score was 100 in 18 patients, 90 in 23, and 80 in 11 patients. No patient had previous chemotherapy. Thirty-four patients had breast cancer and received fluorouracil 500 mg/m2, epirubicin 100 500 mg/m2, and cyclophosphamide 500 mg/m2. Twelve patients had small cell lung cancer and received carboplatin 400 mg/m2 + etoposide 120 mg/m2 x 3 days. Twenty patients with ovarian cancer received carboplatin 350 mg/m2 and cyclophosphamide 500 mg/m2. Ten patients had cancer of unknown primary and received carboplatin 400 mg/m2, epirubicin 60 mg/m2, and etoposide 120 mg/m2 x 3 days. The OND schedule consisted of methylprednisolone 40 mg intravenous bolus followed by OND 8 mg in a 15-min infusion before chemotherapy, followed by OND 4 mg orally x 3 on the same and the next 2 days. Patients who did not experience nausea and vomiting with OND continued with an MCP schedule consisting of methylprednisolone 40 mg bolus followed by MCP 2 mg/kg in a 15-min infusion before chemotherapy, followed by MCP (20 mg x 4 on the day of therapy and the next 2 days after). Patients who failed with MCP or OND continued with OND. Considering our results as a whole, the intensity of nausea does not appear to influence the results of Gralla's scale. The results of Gralla's scale do not appear to be affected by the analysis of the antiemetic results and nausea on the next 2 days following chemotherapy administration. Overall, patients received 145 cycles with OND and 159 cycles with MCP. Of the 76 patients receiving OND-based antiemetic regimen during the first cycle, 13 (21%) experienced severe vomiting (Grade 2, 3) and the remaining 63 (79%) had mild or no vomiting (Grade 0, 1). Patients with Grade 0, 1 vomiting (63, 83%) continued with MCP in the second cycle. The final number of patients who failed on MCP, after 4 cycles of chemotherapy increased to 33 (43%); 43 (57%) were able to complete chemotherapy with MCP. Headache occurred in 15 (10%) cycles with OND and 8 (5%) with MCP. Flushing was noted in 12 (8%), and constipation occurred in 43 (30%) of OND cycles, and extrapyramidal manifestations occurred in 3 (5%) of patients receiving MCP. Diarrhea was noted in 3 (2%) of cycles with OND and in 28 (18%) with MCP. The cost ratio between MCP and OND was 1:14. If we administered OND only in patients who needed it, the overall cost decreased to 44%. Following the strategy applied in the present study, the cost decreased to 47%.
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PMID:Antiemetic prophylaxis with ondansetron and methylprednisolone vs metoclopramide and methylprednisolone in mild and moderately emetogenic chemotherapy. 1051 44

Clinical studies have traditionally identified treatment-specific side effects by comparison of voiced side effects in treatment and placebo arms of a study. Highly motivated women in a clinical trial may underreport drug-induced symptoms for medications which may be considered lifesaving. Affective symptoms during treatment of early breast cancer with tamoxifen (an estradiol receptor antagonist) were reported as infrequent by the manufacturer. However, reports suggest a higher rate of depression during general use. The objective of the present study was to examine the frequency of symptoms that might be side effects of tamoxifen and to relate them to the way the women attributed such symptoms. The exploratory study involved semistructured telephone interviews of 25 women who were taking tamoxifen. Textual analysis of the information was used to examine the symptoms described by the women. They were also asked whether any symptoms were related to the medication. The symptoms and their attribution were evaluated against a background of self-perceived stress. The principal finding was a pattern of ambivalence in attributing symptoms to the drug. Of all the symptomatic changes noted, the women only attributed 51% to tamoxifen. Flushes, fatigue, and depression were reported most frequently during treatment; flushes were readily attributed to tamoxifen but depression and fatigue were attributed to another factor by half of the symptomatic women. Women who reported moderate to high levels of life stress were less likely to attribute symptoms to drug therapy. The results suggest that women taking tamoxifen may not attribute known drug side effects to use of the medication.
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PMID:Tamoxifen in breast cancer: symptom reporting. 1132 15

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
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PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered to 23 patients with locally advanced breast cancer (including 13 cases of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v. followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2 and every 3 weeks repeatedly. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Two to 4 cycles were used. Ten out of 23 patients had a complete response, 10 had partial response, and 3 had no change. The response rate was 87% (20/23). Six out of 23 patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized after neo-adjuvant chemotherapy. The major toxicities included neutropenia, myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia and flushing to the face. However, these were well tolerated in these patients.
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PMID:[Clinical evaluation of effects from neo-adjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer]. 1214 94


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