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)

The efficacy of tropisetron, a new 5-HT3 receptor antagonist, was evaluated in a group of 15 children with a variety of malignant tumours. The majority of children (14/15) received fractionated chemotherapy and on day one complete control of acute nausea and vomiting was observed in 68.7% of all patients with a single, 15-minute, i.v. infusion of tropisetron. Partial control of vomiting was observed in 25% of patients and of nausea in 31.3% of patients on Day 1. Complete control of delayed nausea and vomiting was more variable, with an observed range between 50%-81% of patients over Days 2-6. There was no loss of appetite in 75% of patients treated with tropisetron on Day 1 and, more variably, in 62%-87% of patients on Days 2-6. Side effects were recorded in 18.8% of chemotherapy cycles, the most significant being insomnia in 12.5% of cycles and slight fever in 6.3% of cycles. It was concluded that tropisetron was well suited for children and could be recommended for those receiving a high burden of fractionated chemotherapy.
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PMID:Tropisetron in the control of nausea and vomiting induced by combined cancer chemotherapy in children. 836 98

Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. In some patients the drug was administered orally on the day before treatment. On Day 1 of Course 1, 64.7% of patients had a complete response to tropisetron, i.e. no nausea or vomiting, and 26.9% of patients had a partial response. More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients.
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PMID:Compassionate use of tropisetron in patients at high risk of severe emesis. 836

The anti-emetic efficacy and safety of granisetron, a highly selective and potent 5-HT3 receptor antagonist, was compared with that of high-dose metoclopramide plus dexamethasone in 281 patients due to receive single-day cisplatin chemotherapy (> or = 49 mg m-2). In this single-blind, multicentre study, granisetron (40 micrograms kg-1) was administered as a single prophylactic 5-min infusion. Dexamethasone (12 mg) was administered as a 30-min infusion followed by a loading dose of 3 mg kg-1 metoclopramide. A maintenance dose of metoclopramide 4 mg kg-1 was then infused over 8 h. A single prophylactic dose of granisetron was as effective as the combination regimen in the prevention of cisplatin-induced emesis. Of 143 granisetron-treated patients, 100 (70%) were complete responders (no vomiting and no or only mild nausea) compared with 93/138 (67%) patients who received the comparator regimen. Twenty-three percent of granisetron-treated patients experienced one of more adverse events compared with 33% of patients in the comparator group. No extrapyramidal reactions were reported in the granisetron group compared with 13 in comparator-treated patients (8%). This difference was significant (P < 0.05). The commonest adverse event in the granisetron group, headache (9.8%) described by the majority of patients as mild, was significantly higher than that reported in the comparator group (3% P = 0.02). Granisetron appears to be a safe and effective agent which can be used as a single agent for the prophylaxis of cisplatin-induced emesis. The simplicity of administration, a single 5-min infusion prior to chemotherapy, and the lack of somnolence or extrapyramidal reactions offer clear advantages over the comparator combination regimen.
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PMID:The control of acute cisplatin-induced emesis--a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone. Granisetron Study Group. 839 4

Despite recent advances in control of acute emesis, delayed nausea and vomiting following cisplatin-based chemotherapy remain a significant cause of treatment-related morbidity. Ondansetron, a selective 5HT3 receptor antagonist, is effective in preventing acute emesis in the initial 24-h period following high-dose cisplatin. The efficacy and safety of ondansetron in preventing the delayed emesis syndrome during days 2-5 after cisplatin (> or = 100 mg/m2) were evaluated in a double-blind, placebo-controlled multicentre trial. 50 patients having two or fewer emetic episodes during the first 24 h were randomised to receive ondansetron (16 mg) or placebo orally three times daily beginning 24 h after cisplatin. Rates of complete control of emesis were higher in ondansetron-treated patients during each study day, 59-78%, compared with 39-50% in placebo-treated patients, but the differences were statistically superior only on the third study day (P = 0.009). 40% of patients in the ondansetron treatment arm and 33% treated with placebo had complete control of emesis during the entire 4-day study period (P = 0.648). Withdrawal from study due to nausea and vomiting occurred in 13% of ondansetron-treated patients compared with 33% in the placebo arm (P = 0.102). Control of nausea was better with ondansetron, but differences were not statistically significant. Adverse effects of oral ondansetron given in this dose schedule were minimal. These data suggest that the delayed emesis syndrome may be partially mediated through the 5HT3 receptor, but that a serotonin antagonist alone provides inadequate control. Further investigation of ondansetron-based therapy in this clinical setting is warranted.
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PMID:Delayed emesis following high-dose cisplatin: a double-blind randomised comparative trial of ondansetron (GR 38032F) versus placebo. 842 24

This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted.
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PMID:Randomized comparison of the antiemetic efficacy of a serotonin type 3 receptor antagonist (MDL 72,222) with a high-dose metoclopramide regimen. 845 14

Nausea and vomiting are among the most frequent and severe acute side-effects of cytotoxic therapy and are not optimally controlled by conventional antiemetics. This situation warrants the evaluation of new classes of antiemetic agents such as the 5-HT3 receptor antagonists. 19 children with a median age of 9 years (range 2-16 years), treated with cytotoxic drug combinations that had previously caused nausea and vomiting refractory to conventional antiemetics, were given the selective 5-HT3 receptor antagonist ICS 205-930. The drug was given intravenously (i.v.) at 0.2 mg/kg (maximum 5 mg) during the chemotherapy infusion period and was continued orally for up to 5 days in chemotherapy courses containing cisplatin. The number of emetic episodes was recorded and the response was scored according to following scale: grade 1 = no nausea, no emetic episode; grade 2 = up to four episodes of vomiting and less than 5 h of nausea; grade 3 = five or more than five emetic episodes and/or nausea for at least 5 h. The 19 patients received a total of 169 various courses of chemotherapy combined with ICS 205-930. A score of 3 was observed during one course only, a score of 2 in 37 out of the 169 courses, including the four courses with cisplatin. The drug was very well tolerated. Side-effects possibly related to ICS 205-930 were mild to moderate headache in 4 patients during seven courses overall and obstipation in 3 patients during 11 courses. The results strongly suggest that ICS 205-930 is a highly effective and safe antiemetic agent in non-naive pediatric patients receiving non-cisplatin cytotoxic chemotherapy and who had failed conventional antiemetic treatment.
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PMID:Prevention of emesis by ICS 205-930 in children receiving cytotoxic chemotherapy. 848 76

We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its use in 15 children with malignant disease who received cisplatin (CDDP) either alone (1/15) or in combination (14/15) with other cytostatic drugs. Tropisetron was given to 15 children (8 boys and 7 girls, ranging from 6 months to 17 years of age) with miscellaneous neoplasms. Generally, tropisetron (5 mg/m2/day, maximum 5 mg/day) was administered intravenously the first day of CDDP-based chemotherapy and orally for 4 subsequent days of chemotherapy. The dose of tropisetron was reduced to 0.2 mg/kg/day in children less than 1 year of age and/or those weighing less than 10 kg. Vomiting and nausea were controlled completely in 8 of 15 (53.3%) children on day 1 with a single intravenous infusion of tropisetron. Partial control was observed in 40% of patients on day 1. Complete control of delayed nausea and vomiting ranged between 40% and 80% in patients over days 2 to 5. The results obtained during administration of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of malignant disease in pediatric patients.
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PMID:Prevention of emesis by tropisetron in children receiving combined chemotherapy with cisplatin. 851 33

The field of high-dose chemotherapy with stem cell transplantation has been expanded recently as a treatment for solid tumors and hematological malignancies. Severe emesis remains one of the main extramedullary side-effects of high-dose regimens during the first week of treatment. Traditional antiemetics such as chlorpromazine, diazepam, and phenothiazines are extensively used but are unable to control emesis. The new antiemetic ondansetron, a serotonin receptor (5HT3) antagonist appears to be superior to these drugs for cisplatin-induced emesis. The study we present here is an attempt to control emesis following high-dose regimens, during bone marrow or peripheral stem cell transplantation, with ondansetron. To our knowledge no other paper has reported the efficacy of this antiemetic in such group of patients. A total of 29 patients who received highly emetogenic polychemotherapy as conditioning regimens for bone marrow transplantation were treated with ondansetron, which was given as an 8-mg i.v. short infusion prior the initiation of treatment and every 6 h thereafter for 3 days, and an 8-mg dose every 8 h for 5 additional days. All the patients had previously been treated with chemotherapy and were evaluable for response and toxicity. Complete and major protection of vomiting on day 1 was achieved by 76% of the patients, 58% on day 2 and 52% on day 3. Nausea was absent or mild in 79% of patients on day 1, 45% on day 2 and 41% on day 3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase II study of ondansetron as antiemetic prophylaxis in patients receiving high-dose polychemotherapy and stem cell transplantation. 852 Aug 76

From a consideration of the above evidence, it is possible to hypothesize that the 5-HT3 receptors, which are located both in the gut and in the AP/NTS, may play an important and perhaps pivotal part in the mechanism(s) of action of chemotherapy and radiotherapy to induce emesis in animals and humans and represent the anti-emetic sites of action of ondansetron and related agents (see Fig. 1). The value of ondansetron and the 5-HT3 receptor antagonists has been to greatly improve the treatment of nausea and emesis in the cancer patient and to cause a renaissance in emesis research. The 5-HT3 receptor antagonists have helped to redefine the phases of chemotherapy induced emesis and establish the first clear neurotransmitter links in the emetic reflex. It has also encouraged the analysis of emetic mechanisms that will identify further points for pharmacological intervention that may ultimately provide "broad spectrum" anti-emetic agents. Such compounds would further improve the quality of life and treatment of the cancer patient, leading to increased success in the treatment of malignant tumours.
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PMID:Emesis and anti-emesis. 856 88

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.
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PMID:Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting. 865 23


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