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)

The safety and efficacy of intravenous granisetron were compared with combinations of conventional antiemetics in two single-blind, parallel-group studies which have been reported previously. In this review updated data from both studies is presented. In both studies granisetron (40 micrograms/kg) was given as a single 5-min infusion before chemotherapy with two additional doses allowed to control subsequent nausea and vomiting. All patients were naive to chemotherapy. Patients due to receive cisplatin (greater than 49 mg/m2) were randomly assigned to receive either granisetron alone or metoclopramide (3 mg/kg) plus dexamethasone (12 mg) given prophylactically followed by an 8-h infusion of metoclopramide (4 mg/kg). In the 24 h after the start of chemotherapy 70% of granisetron-treated patients and 67% of comparator group were complete responders. In patients due to receive moderately emetogenic chemotherapy, granisetron was compared with chlorpromazine (up to 200 mg/24 h) plus dexamethasone (12 mg). Twenty-four hour efficacy was significantly higher in the granisetron group with complete response in 68% of patients compared to 47% in the comparator group (P less than 0.001). A subset of 40 patients in this study were crossed over to receive the alternative antiemetic on their next cycle of chemotherapy. A significant majority of patients (32/34; 94%) preferred granisetron (P less than 0.001). Around 80% of the granisetron-treated patients in both groups required only a single prophylactic dose of granisetron. Following the first additional dose of granisetron, around 87% of patients reported symptoms to be improved or resolved. Adverse experience reporting was higher in the comparator groups with somnolence and extrapyramidal reactions representing the most common events. Headache was the most commonly reported adverse experience in granisetron-treated patients. Granisetron has proved safe and effective in controlling chemotherapy-induced emesis and is more convenient to administer than conventional antiemetics.
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PMID:A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group. 132 Sep 13

Two randomised single-blind comparative studies were carried out in patients receiving 5-day fractionated chemotherapy. The first which has been reported previously [1] compared granisetron (40 micrograms/kg) (n = 103) with alizapride (12 mg/kg) plus dexamethasone (8 mg) (n = 94) while the second compared granisetron (40 micrograms/kg) (n = 143) with metoclopramide (7 mg/kg) plus dexamethasone (12 mg) (n = 141). Granisetron, unlike alizapride or metoclopramide is a specific 5-HT3 antagonist. The percentage of complete responders (patients with no vomiting and no worse than mild nausea) over the 5-day treatment period was higher for granisetron than for alizapride/dexamethasone (54% vs. 42.7%) (P = 0.121) or for metoclopramide/dexamethasone (46.8% vs. 43.9%). The percentage of complete responders in the first 24 h was significantly higher for granisetron (90.3%) than for alizapride/dexamethasone (65.9%) (P less than 0.001) or for metoclopramide/dexamethasone (87.4% vs. 67.9% P less than 0.0001). Granisetron was also superior to both comparators in terms of the time to the first episode of moderate/severe nausea and to less than a complete response. Significantly fewer granisetron patients were withdrawn than in the alizapride/dexamethasone group (P = 0.017) or the metoclopramide/dexamethasone group (P less than 0.0001). In both studies more comparator patients were withdrawn due to lack of efficacy and adverse events. Significantly fewer granisetron patients experienced adverse events than in either the alizapride/dexamethasone group (47.6% vs. 61.7%, P = 0.047) or the metoclopramide/dexamethasone group (60.8% vs. 77.3% P = 0.003). Granisetron patients experienced a significantly higher occurrence of constipation in both studies (10.7% vs. 3.2% and 12.6% vs. 2.8%). Headache and fever were also more frequent in the granisetron group, while extrapyramidal effects, reported by 5.3% of the alizapride/dexamethsone group and 20.6% of the metoclopramide/dexamethasone group, were not reported in any granisetron patients.
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PMID:Fractionated chemotherapy--granisetron or conventional antiemetics? The Granisetron Study Group. 132 Sep 16

Three double-blind, dose-ranging studies, involving 996 chemotherapy-naive patients, were conducted to determine the optimal prophylactic dose of intravenous (i.v.) granisetron for prevention of cytotoxic-induced emesis. The antiemetic efficacy of prophylactic i.v. granisetron doses ranging from 2-40 micrograms/kg (study 1) and 40-160 micrograms/kg (study 2) were examined in patients receiving high-dose cisplatin regimens. In study 3, i.v. doses of 40 and 160 micrograms/kg were compared in patients receiving other emetogenic cytotoxic therapies. In study 1, 67.9% (36/53) of patients were complete responders at 24 h following the 40 micrograms/kg dose compared with 61.5% (32/52) and 30.8% (16/52) in the 10 and 2 micrograms/kg groups, respectively (40 vs. 2 micrograms/kg; P less than 0.001). There were no significant differences between doses of 40 and 160 micrograms/kg in any efficacy parameter in Studies 2 and 3. Granisetron was well tolerated across the dose range examined and no dose-related toxicity was observed. In conclusion, a single 40 micrograms/kg prophylactic dose provides optimal control of cytotoxic-induced nausea and vomiting. A simple 3 mg single-dose i.v. regimen (equivalent to 40 micrograms/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.
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PMID:Intravenous granisetron--establishing the optimal dose. The Granisetron Study Group. 132 Sep 19

Granisetron is a new serotonin-receptor antagonist with considerable activity in preclinical models and early clinical studies against drug-induced nausea and vomiting. In a randomized, double-blind trial, two dose levels of granisetron were compared with regard to their efficacy and safety if given to patients receiving emetogenic chemotherapy with or without cisplatin. The present paper reports the Dutch experience with 125 patients included in this international trial. The two dose levels (40 and 160 micrograms/kg given once i.v. prior to chemotherapy) were equally effective in preventing acute emesis and nausea (within the first 24 h); in the group receiving cisplatin doses of 50 mg/m2 or more, 39% of patients had a complete response (no vomiting and mild nausea at most), with a complete response rate of 82% in the patients receiving moderately emetogenic chemotherapy. Sixty-three percent of patients receiving highly emetogenic chemotherapy with a complete response within 24 h lost this response during the next 6 days, as did 20% of the other patients. Headache was the most frequently reported adverse event (18%), followed by constipation (6%) and dizziness (4%). All adverse events were mild and occurred equally frequently at both dose levels. Granisetron at 40 micrograms/kg i.v. given once is effective in the prevention of acute chemotherapy-induced emesis and nausea, in particular in patients receiving moderately emetogenic therapy.
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PMID:A randomized trial of two doses of granisetron in the treatment of chemotherapy-induced emesis. Dutch results within a multinational study. 133 30

151 patients (149 evaluable) receiving their first course of chemotherapy containing cisplatin in a dose of at least 50 mg/m2 were randomised to receive either a single dose of intravenous granisetron 80 micrograms/kg or intravenous metoclopramide 2 mg/kg every 2 h for five doses plus a single dose of dexamethasone 10 mg and diphenhydramine. After 24 h, there was no significant difference between groups with respect to nausea or vomiting: in the granisetron group 46% of patients had no emesis, versus 44% of the standard group. Granisetron is an antiemetic agent with efficacy similar to that of high-dose metoclopramide plus dexamethasone.
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PMID:A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial. 133 37

In an open ascending-dose study, granisetron, a specific 5-HT3 receptor antagonist, was administered to 24 paediatric patients (17 male, 7 female, mean age 6.2, range 3-15 years) who were receiving moderately or highly emetogenic chemotherapy for malignant disease. Single doses of 10, 20 and 40 micrograms/kg were administered by intravenous infusion 1 h before chemotherapy. Each dose level was studied in a group of 8 patients. With the 40 micrograms/kg dose, 5 of 8 patients experienced no nausea or vomiting in the 24 h after granisetron treatment. With 20 micrograms/kg, a similar response was seen, but with 10 micrograms/kg only 2 of 8 patients experienced complete antiemetic protection despite additional prophylactic chlorpromazine in this group. Granisetron was very well tolerated, and there were no clinically important changes in pulse rate, blood pressure or Holter electrocardiogram. It is concluded that granisetron was very well tolerated by paediatric patients. In addition, there was clear evidence of a major antiemetic effect for at least 24 h after a single intravenous dose of 20 or 40 micrograms/kg.
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PMID:Efficacy and safety of granisetron in the prevention of chemotherapy-induced emesis in paediatric patients. 165 48

Granisetron (BRL 43694) is a highly selective 5-HT3 receptor antagonist which possesses significant antiemetic activity, likely mediated through antagonism of 5-HT3 receptors on abdominal vagal afferents and possibly in or near the chemoreceptor trigger zone. Clinical trials in cancer patients demonstrate that, compared with placebo, granisetron significantly reduces the incidence of nausea and vomiting for 24 hours after administration of high-dose cisplatin. In large comparative trials, 70% of patients who received granisetron prior to cisplatin or other chemotherapy experienced complete inhibition of vomiting with little or no nausea for 24 hours after antineoplastic administration; these results were similar to those obtained with high-dose metoclopramide plus dexamethasone, and superior to a combination of chlorpromazine plus dexamethasone, or prochlorperazine plus dexamethasone, or methylprednisolone monotherapy. The most frequently reported adverse event associated with granisetron administration is headache which occurs in about 10 to 15% of patients while constipation, somnolence, diarrhoea and minor transient changes in blood pressure have been reported less frequently. Extrapyramidal effects, which can occur with high-dose metoclopramide and may be a limiting factor in its use, have not been noted with granisetron administration. Thus, granisetron is an effective, well tolerated and easily administered agent for the prophylaxis of nausea and vomiting induced by cancer chemotherapy which appears to be devoid of extrapyramidal side effects associated with metoclopramide. As a member of a new class of drugs, the selective 5-HT3 receptor antagonists, granisetron provides the medical oncologist with a new, potentially more acceptable antiemetic therapy.
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PMID:Granisetron. A review of its pharmacological properties and therapeutic use as an antiemetic. 172 76

In this double-blind study, the efficacy and safety of a novel anti-emetic, granisetron, was assessed at two dose levels (40 micrograms/kg; n = 149 and 160 micrograms/kg; n = 147) in 296 patients undergoing high-dose cisplatin chemotherapy. In the first 24 h, 57% and 60% of patients, respectively, experienced no vomiting and no more than mild nausea. Two further doses of granisetron (40 micrograms/kg) were permitted in the first 24 h to treat breakthrough nausea and vomiting. This resulted in resolution or improvement of symptoms in 68-89% of patients. Over the 7-day study period, 53% of patients in the lower-dose group and 51% in the higher received no conventional anti-emetic therapy. No difference in efficacy or safety between the two doses of granisetron was established. Granisetron was well tolerated throughout the dose range of the study (40-240 micrograms/kg). The commonest adverse event was headache, seen in 13-16% of patients. In all cases this resolved spontaneously or responded to simple treatment.
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PMID:A comparison of two dose levels of granisetron in patients receiving high-dose cisplatin. The Granisetron Study Group. 216 79

The efficacy and safety of granisetron, a novel anti-emetic, were compared with those of high-dose metoclopramide plus dexamethasone in 234 patients undergoing treatment with high-dose cisplatin (greater than or equal to 49 mg/m2). In this single-blind study, granisetron (40 micrograms/kg; n = 114) was administered as a 5 min infusion, with two additional 40 micrograms/kg doses allowed to control any subsequent nausea and vomiting. In 120 patients, dexamethasone 12 mg was administered intravenously over 30 min, followed by a loading dose of 3 mg/kg metoclopramide. Metoclopramide maintenance dose of 4 mg/kg was then administered over 8 h. The single 5 min infusion of granisetron was at least as effective an anti-emetic as the standard regimen. Approximately 70% of patients in each treatment group were free from vomiting and had no, or only mild nausea in the first 24 h. Granisetron administration was more convenient than the combination dosing schedule for the comparator which was up to 9 h. Only one adverse event, headache, occurred in more than five patients in the granisetron group. However, 13 extrapyramidal reactions (five of them serious) were reported in the metoclopramide plus dexamethasone group.
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PMID:Efficacy and safety of granisetron compared with high-dose metoclopramide plus dexamethasone in patients receiving high-dose cisplatin in a single-blind study. The Granisetron Study Group. 216 84

The clinical research programme with granisetron has involved a total of 1,229 patients, 982 receiving granisetron, 233 receiving currently available combination regimens and 14 receiving placebo. The true efficacy of granisetron was evaluated in a placebo-controlled trial with granisetron given prophylactically and being available as rescue medication in the placebo group. Granisetron produced a complete anti-emetic response in 92.9% of patients and was effective as intervention for the emesis experienced by the patients in the placebo group. Dose-finding studies have confirmed the wide therapeutic margin with four-fold increases in dose producing comparable results. In patients receiving high-dose cisplatin chemotherapy, two out of every three patients responded to a single prophylactic dose; which demonstrates granisetron's long duration of action (greater than 24 h). Additional granisetron also demonstrated benefit if the initial dose failed or delayed-onset emesis occurred. These results are also seen with other emetogenic regimens. Granisetron produces a greater degree of control than the anti-emetic combinations of metoclopramide/dexamethasone or dexamethasone/chlorpromazine. The side-effect profile in volunteers was favourable. The profile in patients is more difficult to define due to the range of potent drugs which cancer chemotherapy patients receive. Headache and constipation were the most common effects with granisetron, although the former was treatable with simple analgesics and the latter thought to be related to higher doses and subsided spontaneously. The future is promising, with the possible introduction of a fixed 3 mg i.v. dose administered over 5 min followed by oral maintenance therapy if and when required.
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PMID:An overview on the use of granisetron in the treatment of emesis associated with cytostatic chemotherapy. 216 85


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