human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The antiemetic effectiveness of 5-HT3 receptor antagonists in combination with dexamethasone in patients receiving short-term infusion chemotherapy has been well demonstrated . Less information is available about the efficacy of the same antiemetic combination in patients treated with regimens of chemotherapy in which the drugs are delivered in continuous infusion of several hours . The purpose of this study was to report the effectiveness of a double administration of antiemetic drugs in patients treated with strong emesis-inducing drugs for several days . In this study , 19 male and 13 female patients with osteosarcoma , ages 9 to 45 years , treated with chemotherapy  , received intravenous tropisetron 5 mg plus dexamethasone 8 mg every 12 hours during the first two cycles of the preoperative treatment : cisplatin 120 mg/m2 over 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours and continuous infusion of ifosfamide 15 g/m2 over 120 hours . The assessment of the antiemetic efficacy was performed three times every day : from 8:00 am to 4:00 pm , from 4:00 pm to 12:00 am , and from 12:00 am to 8:00 am . The patients were followed from the beginning of the treatment until 2 hours after its end , when they were discharged from hospital . Complete protection from emesis was obtained in 80 % of the 256 days of treatment : 81 % during the first cycle ( cisplatin 120 mg/m2 in 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours ) and 79 % during the second cycle ( continuous infusion of ifosfamide 15 g/m2 in 120 hours ) . In both cycles , complete protection declined from the first to the last day of treatment ( from 100 % to 62 % during the first cycle and from 100 % to 63 % during the second cycle ) . These results indicate that when chemotherapy is administered in a protracted infusion , higher doses of antiemetic agents are necessary to achieve acceptable antiemetic activity The selective 5-hydroxytryptamine3 ( 5HT3 ) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy . This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose ( ≥100 mg/m2 ) cisplatin chemotherapy . A total of 125 patients were r and omized ( 1∶1∶1 ) to receive 0.015 , 0.15 , or 0.30 mg/kg every 4 h for a total of 3 doses . All patients were monitored for emetic episodes , adverse events , and laboratory safety parameters for 24 h following cisplatin administration . The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes ( P=0.033 ) and complete response ( no emetic episodes , P=0.005 ) . No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups . The most common adverse event was headache . Three 0.15-mg/kg doses of intravenous ondansetron are safe , effective , and adequate for the control of cisplatin-induced emesis Granisetron ( GRN ) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea . The , pharmacokinetics of GRN  has not been fully evaluated in such patients , however , and its dosage regimen is still controversial . In this study , we determined  GRN  levels in serum and urine from lung cancer patients and children suffering from cancer after intravenous infusion . In lung cancer patients , the interindividual variations in t(1/2beta ) , area under the concentration-time curve ( AUC ) , and Vd(beta ) were relatively smaller than expected from previous reports on healthy subjects , while t(1/2beta ) was prolonged more than 5-fold in healthy subjects . Urinary excretion of unchanged GRN  in lung cancer patients was ca . 15 % of dose , consistent with previous reports , and one individual demonstrated an even higher urinary excretion ( ca . 45 % ) . The pharmacokinetic parameters of GRN  in child cancer patients varied markedly among individuals , and some child patients had smaller t(1/2beta ) than adult patients . In these cases , GRN should be administered at shorter intervals . These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea BACKGROUND The localization of substance P in brain-stem regions associated with vomiting , and the results of studies in ferrets , led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy . METHODS In a multicenter , double-blind , placebo-controlled trial involving 159 patients who had not previously received cisplatin  , we evaluated the prevention of acute emesis ( occurring within 24 hours ) and delayed emesis ( on days 2 to 5 ) after a single dose of cisplatin therapy ( 70 mg or more per square meter of body-surface area ) . Before receiving cisplatin , all the patients received granisetron ( 10 microg per kilogram of body weight intravenously ) and dexamethasone ( 20 mg orally ) . The patients were r and omly assigned to one of three treatments in addition to granisetron and dexamethasone : 400 mg of an oral trisubstituted morpholine acetal ( also known as L-754,030 ) before cisplatin and 300 mg on days 2 to 5 ( group 1 ) , 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 ( group 2 ) , or placebo before cisplatin and placebo on days 2 to 5 ( group 3 ) . Additional medication was available at any time to treat occurrences of vomiting or nausea . RESULTS In the acute-emesis phase , 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting ( P<0.001 ) . In the delayed-emesis phase , 82 percent of the patients in group 1 , 78 percent of those in group 2 , and 33 percent of those in group 3 had no vomiting ( P<0.001 for the comparison between group 1 or 2 and group 3 ) . The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 ( P=0.003 ) . No serious adverse events were attributed to L-754,030 . CONCLUSIONS The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin . Moreover , combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin  were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with mild sedation frequently observed ; one patient had a brief extrapyramidal reaction . We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy Prior studies in adults have shown that metoclopramide ( MCP ) , when given in high intravenous ( IV ) doses ( 2 mg/kg ) , is a highly effective antiemetic for chemotherapy-induced vomiting . It is well-tolerated in older adults , but younger adults have an increased disposition to acute extrapyramidal reactions ( EPRs ) . Before study ing the efficacy of MCP as an antiemetic in children , we first had to establish the safe dose range . We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin ( 120 mg/m2 ) or cyclophosphamide ( greater than 900 mg/m2 ) , beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg .  MCP was given every two hours for four doses beginning one-half hour before chemotherapy . To reduce the incidence of EPRs , we added concomitant diphenhydramine . In MCP doses less than 2 mg , toxicity was minimal . In doses greater than or equal to 2 mg , 4/27 ( 15 % ) had EPRs and 9/27 ( 33 % ) had akathisia . Children who received two consecutive days of MCP had a higher frequency of EPRs .  Metoclopramide ( 2 mg/kg ) had promising antiemetic efficacy in a preliminary nonr and omized trial . Chemotherapy-experienced children vomited fewer than five times in 9/21 ( 43 % ) trials , and new patients vomited fewer than five times in 7/10 ( 70 % ) trials . MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed . Chemotherapy-induced emesis has the same negative implication s in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting r and omized clinical trials in children BACKGROUND There are few r and omised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy . The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo . MATERIAL S AND METHODS One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study . The patients recorded daily emesis , nausea and bowel habit and grade d weekly symptoms of nausea , vomiting , diarrhoea and lack of appetite . The EORTC C30 question naire was completed . RESULTS 67 % of patients given ondansetron had complete control of emesis compared with 45 % of patients with placebo ( P < 0.05 ) . The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group ( P < 0.01 ) . Patients given ondansetron had fewer days with emesis and nausea compared with placebo ( P < 0.05 ) . The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group ( P < 0.05 ) . This difference persisted during the first three weeks , but not thereafter . Similarly , some quality of life measures showed significant differences in favour of the ondansetron group . More patients ( n = 13 ) withdrew due to lack of efficacy in the placebo group compared with patients ( n = 8) in the ondansetron group . CONCLUSIONS The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen Palonosetron , a highly selective and potent 5‐HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half‐life ( approximately 40 hours ) , has shown efficacy in Phase II trials in preventing  chemotherapy‐induced nausea and vomiting ( CINV )  result ing from highly emetogenic chemotherapy . The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy PURPOSE To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours ; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours ; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy . PATIENTS AND METHODS This was a multicenter , double-blind , r and omized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients . In arm 1 , dolasetron ( 2.4 mg/kg ) was given intravenously ( I.V. ) prechemotherapy , followed 24 hours later by oral dolasetron ( 200 mg once daily ) for 6 days . Arms 2 and 3 consisted of dolasetron and dexamethas 
    Output:
    
agent
For persons receiving chemotherapy of high emetic risk , there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics .
In all patients receiving cisplatin and all other agents of high emetic risk , the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis .
The Up date Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The antiemetic effectiveness of 5-HT3 receptor antagonists in combination with dexamethasone in patients receiving short-term infusion chemotherapy has been well demonstrated . Less information is available about the efficacy of the same antiemetic combination in patients treated with regimens of chemotherapy in which the drugs are delivered in continuous infusion of several hours . The purpose of this study was to report the effectiveness of a double administration of antiemetic drugs in patients treated with strong emesis-inducing drugs for several days . In this study , 19 male and 13 female patients with osteosarcoma , ages 9 to 45 years , treated with chemotherapy  , received intravenous tropisetron 5 mg plus dexamethasone 8 mg every 12 hours during the first two cycles of the preoperative treatment : cisplatin 120 mg/m2 over 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours and continuous infusion of ifosfamide 15 g/m2 over 120 hours . The assessment of the antiemetic efficacy was performed three times every day : from 8:00 am to 4:00 pm , from 4:00 pm to 12:00 am , and from 12:00 am to 8:00 am . The patients were followed from the beginning of the treatment until 2 hours after its end , when they were discharged from hospital . Complete protection from emesis was obtained in 80 % of the 256 days of treatment : 81 % during the first cycle ( cisplatin 120 mg/m2 in 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours ) and 79 % during the second cycle ( continuous infusion of ifosfamide 15 g/m2 in 120 hours ) . In both cycles , complete protection declined from the first to the last day of treatment ( from 100 % to 62 % during the first cycle and from 100 % to 63 % during the second cycle ) . These results indicate that when chemotherapy is administered in a protracted infusion , higher doses of antiemetic agents are necessary to achieve acceptable antiemetic activity The selective 5-hydroxytryptamine3 ( 5HT3 ) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy . This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose ( ≥100 mg/m2 ) cisplatin chemotherapy . A total of 125 patients were r and omized ( 1∶1∶1 ) to receive 0.015 , 0.15 , or 0.30 mg/kg every 4 h for a total of 3 doses . All patients were monitored for emetic episodes , adverse events , and laboratory safety parameters for 24 h following cisplatin administration . The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes ( P=0.033 ) and complete response ( no emetic episodes , P=0.005 ) . No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups . The most common adverse event was headache . Three 0.15-mg/kg doses of intravenous ondansetron are safe , effective , and adequate for the control of cisplatin-induced emesis Granisetron ( GRN ) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea . The , pharmacokinetics of GRN  has not been fully evaluated in such patients , however , and its dosage regimen is still controversial . In this study , we determined  GRN  levels in serum and urine from lung cancer patients and children suffering from cancer after intravenous infusion . In lung cancer patients , the interindividual variations in t(1/2beta ) , area under the concentration-time curve ( AUC ) , and Vd(beta ) were relatively smaller than expected from previous reports on healthy subjects , while t(1/2beta ) was prolonged more than 5-fold in healthy subjects . Urinary excretion of unchanged GRN  in lung cancer patients was ca . 15 % of dose , consistent with previous reports , and one individual demonstrated an even higher urinary excretion ( ca . 45 % ) . The pharmacokinetic parameters of GRN  in child cancer patients varied markedly among individuals , and some child patients had smaller t(1/2beta ) than adult patients . In these cases , GRN should be administered at shorter intervals . These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea BACKGROUND The localization of substance P in brain-stem regions associated with vomiting , and the results of studies in ferrets , led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy . METHODS In a multicenter , double-blind , placebo-controlled trial involving 159 patients who had not previously received cisplatin  , we evaluated the prevention of acute emesis ( occurring within 24 hours ) and delayed emesis ( on days 2 to 5 ) after a single dose of cisplatin therapy ( 70 mg or more per square meter of body-surface area ) . Before receiving cisplatin , all the patients received granisetron ( 10 microg per kilogram of body weight intravenously ) and dexamethasone ( 20 mg orally ) . The patients were r and omly assigned to one of three treatments in addition to granisetron and dexamethasone : 400 mg of an oral trisubstituted morpholine acetal ( also known as L-754,030 ) before cisplatin and 300 mg on days 2 to 5 ( group 1 ) , 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 ( group 2 ) , or placebo before cisplatin and placebo on days 2 to 5 ( group 3 ) . Additional medication was available at any time to treat occurrences of vomiting or nausea . RESULTS In the acute-emesis phase , 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting ( P<0.001 ) . In the delayed-emesis phase , 82 percent of the patients in group 1 , 78 percent of those in group 2 , and 33 percent of those in group 3 had no vomiting ( P<0.001 for the comparison between group 1 or 2 and group 3 ) . The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 ( P=0.003 ) . No serious adverse events were attributed to L-754,030 . CONCLUSIONS The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin . Moreover , combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin  were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with mild sedation frequently observed ; one patient had a brief extrapyramidal reaction . We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy Prior studies in adults have shown that metoclopramide ( MCP ) , when given in high intravenous ( IV ) doses ( 2 mg/kg ) , is a highly effective antiemetic for chemotherapy-induced vomiting . It is well-tolerated in older adults , but younger adults have an increased disposition to acute extrapyramidal reactions ( EPRs ) . Before study ing the efficacy of MCP as an antiemetic in children , we first had to establish the safe dose range . We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin ( 120 mg/m2 ) or cyclophosphamide ( greater than 900 mg/m2 ) , beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg .  MCP was given every two hours for four doses beginning one-half hour before chemotherapy . To reduce the incidence of EPRs , we added concomitant diphenhydramine . In MCP doses less than 2 mg , toxicity was minimal . In doses greater than or equal to 2 mg , 4/27 ( 15 % ) had EPRs and 9/27 ( 33 % ) had akathisia . Children who received two consecutive days of MCP had a higher frequency of EPRs .  Metoclopramide ( 2 mg/kg ) had promising antiemetic efficacy in a preliminary nonr and omized trial . Chemotherapy-experienced children vomited fewer than five times in 9/21 ( 43 % ) trials , and new patients vomited fewer than five times in 7/10 ( 70 % ) trials . MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed . Chemotherapy-induced emesis has the same negative implication s in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting r and omized clinical trials in children BACKGROUND There are few r and omised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy . The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo . MATERIAL S AND METHODS One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study . The patients recorded daily emesis , nausea and bowel habit and grade d weekly symptoms of nausea , vomiting , diarrhoea and lack of appetite . The EORTC C30 question naire was completed . RESULTS 67 % of patients given ondansetron had complete control of emesis compared with 45 % of patients with placebo ( P < 0.05 ) . The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group ( P < 0.01 ) . Patients given ondansetron had fewer days with emesis and nausea compared with placebo ( P < 0.05 ) . The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group ( P < 0.05 ) . This difference persisted during the first three weeks , but not thereafter . Similarly , some quality of life measures showed significant differences in favour of the ondansetron group . More patients ( n = 13 ) withdrew due to lack of efficacy in the placebo group compared with patients ( n = 8) in the ondansetron group . CONCLUSIONS The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen Palonosetron , a highly selective and potent 5‐HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half‐life ( approximately 40 hours ) , has shown efficacy in Phase II trials in preventing  chemotherapy‐induced nausea and vomiting ( CINV )  result ing from highly emetogenic chemotherapy . The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy PURPOSE To compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours ; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours ; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy . PATIENTS AND METHODS This was a multicenter , double-blind , r and omized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients . In arm 1 , dolasetron ( 2.4 mg/kg ) was given intravenously ( I.V. ) prechemotherapy , followed 24 hours later by oral dolasetron ( 200 mg once daily ) for 6 days . Arms 2 and 3 consisted of dolasetron and dexamethas 
    Output:
    