title: Tropisetron and Dexamethasone Administered Twice Daily for the Prevention of Acute Emesis in Patients Treated With Continuous Infusion of Cisplatin-Doxorubicin and High-Dose Ifosfamide Over 48, 24, and 120 Hours Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis Pharmacokinetics of granisetron in adults and children with malignant diseases. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy. A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Improved prevention of moderately emetogenic chemotherapy‐induced nausea and vomiting with palonosetron, a pharmacologically novel 5‐HT3 receptor antagonist Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy. A multicentre, double-blind, randomised trial comparing ondansetron versus ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis. Efficacy and tolerability of aprepitant for the prevention of chemotherapy‐induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy Ondansetron in radiation therapy of brain tumor in children. Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group. Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy. Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation. A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study. Controlling delayed vomiting: double-blind, randomized trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin. Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial of tropisetron rescue for non-responders to metoclopramide. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study. Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. Efficacy of Oral Ondansetron, A Selective Antagonist of 5‐HT3 Receptors, in the Treatment of Nausea and Vomiting Associated with Cyclophosphamide‐Based Chemotherapies Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia. Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients Oral granisetron with or without methylprednisolone versus metoclopramide plus methylprednisolone in the management of delayed nausea and vomiting induced by cisplatin‐based chemotherapy. A prospective randomized trial Ondansetron compared with dexamethasone and metoclopramide as antiemetics in the chemotherapy of breast cancer with cyclophosphamide, methotrexate, and fluorouracil. Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy‐induced nausea and vomiting Granisetron in the prevention of irradiation-induced emesis. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. On the mechanism of radiation-induced emesis: the role of serotonin. Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy‐induced nausea and vomiting The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group. Prevalence, predictors, and course of anticipatory nausea in women receiving adjuvant chemotherapy for breast cancer The delayed-emesis syndrome from cisplatin: phase III evaluation of ondansetron versus placebo. Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. Predictive Factors of Delayed Emesis in Cisplatin‐Treated Patients and Antiemetic Activity and Tolerability of Metoclopramide or Dexamethasone: A Randomized Single‐Blind Study Role of maintenance oral dexamethasone in prophylaxis of delayed emesis caused by moderately emetogenic chemotherapy. Ondansetron for efficient emesis control during total body irradiation. Development of anticipatory nausea: a prospective analysis. Anticipatory nausea and vomiting: prevalence and predictors in chemotherapy patients. 5-HT3 receptor antagonists in the control of cisplatin-induced delayed emesis.
abstract: 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 dexamethasone 8 mg I.V. , followed 24 hours later by oral dexamethasone ( 8 mg once daily ) in one arm , and oral dexamethasone and dolasetron in the other , also for 6 days . In arms 4 , 5 , and 6 , ondansetron ( 32 mg I.V. or 8 mg orally twice daily ) was administered in a similar manner to arms 1 , 2 , and 3 before and 24 hours after chemotherapy .  Mean nausea severity ( MNS ) was assessed on a visual analog scale ( VAS ) in a daily diary . RESULTS Of 703 patients enrolled , 696 were eligible . There were 343 dolasetron- and 353 ondansetron-treated patients ; 57 % of dolasetron-treated patients had complete protection in the first 24 hours versus 67 % of patients who received ondansetron ( P = .013 ) . MNS was also more pronounced on the dolasetron arm ( P = .051 ) . Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection , compared with 55 % without dexamethasone ( P < .001 ) . MNS was significantly reduced with the addition of dexamethasone ( P < .001 ) . At 7 days , dolasetron and ondansetron had equivalent complete protection rates ( 36 % and 39 % , respectively ) . With the addition of dexamethasone , 48 % of patients compared with 28 % had complete protection ( P < .001 ) . MNS was significantly improved with added dexamethasone ( P < .001 ) . CONCLUSION At the doses used , dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy , but there was no demonstrable difference between both drugs over 7 days . The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy . Cancer patients scheduled to receive for the first time cisplatin ( > 50 mg/m(2 ) ) in combination with other cytotoxic agents , were recruited in a multicentre , r and omised , double-blind study and treated with ondansetron 8 mg i.v . and dexamethasone 20 mg i.v . Twenty-four hours after the start of chemotherapy , patients were r and omised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2 - 5 ( group A ) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2 - 3 , and 4 mg bd on days 4 and 5 ( group B ) . Two hundred and thirty-six cancer patients were recruited into the study . Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39 % and in 63/42 % of patients , respectively in the first course ; in 55/34 % and in 64/40 % in the second and in 49/31 % and 60/37 % in the third . Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone ( P<0.05 ) . The same model , however , shows no difference in incidence of nausea between the two treatment regimens . Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone An aprepitant ( APR ) regimen was evaluated for prevention of  nausea and emesis  due to moderately emetogenic chemotherapy ( MEC ) over multiple cycles Ten children receiving 5 to 6 week courses of radiotherapy after brain tumor surgery were given ondansetron treatment for persistent nausea and emesis . All patients continued the ondansetron treatment until the end of their radiotherapy course . Nausea , emesis , appetite , and adverse events were scored throughout the ondansetron treatment period . Ondansetron was well tolerated by all patients and was effective at reducing symptoms in 60 % of the children PURPOSE To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy .  PATIENTS AND METHODS Four hundred thirty-five eligible and assessable patients were r and omized to one of two arms in a double-blind fashion : arm A ; granisetron 3 mg intravenous ( i.v . ) plus dexamethasone 10 mg i.v . prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours , then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 ( 219 patients ) ; arm B ; as in arm A but with placebo substituted for granisetron on days 2 through 7 ( 216 patients ) . All patients completed diaries in which episodes of emesis and severity of nausea were recorded . RESULTS The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period . CONCLUSION The administration of a 5-hydroxytryptamine3 , receptor ( 5-HT3 ) antagonist , in this case granisetron , after 24 hours conferred no benefit . This negative result needs to be assessed in light of conflicting literature , but at present it does not appear that the routine use of these drugs in this setting is justified PURPOSE The safety , antiemetic efficacy , and pharmacokinetics of single oral doses of dolasetron , a new highly selective 5-HT3 receptor antagonist , were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy .  PATIENTS AND METHODS A total of 32 children , ages 3 to 18 years , were enrolled in a nonr and omized , multicenter , open-label , dose-escalation study . Three oral dose levels ( 0.6 , 1.2 , or 1.8 mg/kg ) were studied . Safety , efficacy , and pharmacokinetic parameters were assessed over 24 hours at each dosage level . RESULTS The most effective dose was 1.8 mg/kg ; 60 % of the patients achieved a complete or major response ( < or = 2 emetic episodes in 24 hours ) . A complete response was achieved in 3 of 9 patients ( 33 % ) who received 0.6 mg/kg , 4 of 13 ( 31 % ) patients who received 1.2 mg/kg , and 5 of 10 ( 50 % ) patients who received 1.8 mg/kg of dolasetron . Overall , dolasetron was well tolerated . Adverse events were mild and similar to those reported in adults . Peak plasma concentrations ( Cmax ) of dolasetron 's active reduced metabolite , MDL 74,156 , were dose proportional and occurred , on the average , within 1 hour of oral administration . The half-life ( t1/2 ) in plasma was approximately 6 hours for all dose levels , and the mean clearance ( CLapp ) was unrelated to dose . CONCLUSIONS Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting , particularly at the 1.8-mg/kg dose level . These results support further evaluation of oral dolasetron in larger r and omized clinical trials in the pediatric cancer population Total body irradiation ( TBI ) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation . Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50 % of patients . In a double blind study of 20 patients undergoing marrow transplantation , a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI . Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients . All patients had received high dose melphalan the previous evening . Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group ( p = 0.029 ) . No significant adverse events were observed . Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI In a multicentre , international double-blind trial , patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were r and omized to receive either oral ondansetron 8 mg t.d.s . or oral prochlorperazine 10 mg t.d.s . throughout their radiation course in order to try to prevent nausea and vomiting . A total of 192 patients were recruited , 135 of whom were included in the efficacy analysis ; of these , 70 received ondansetron and 65 prochlorperazine . Forty-three ( 61 % ) of the patients prescribed ondansetron and 23 ( 35 % ) of those given prochlorperazine had a complete response , with no emetic episodes throughout their treatment course ( P = 0.002 ) . There was , however , no significant difference between the two groups with respect to the incidence and severity of nausea . Seventeen ( 24 % ) of the patients on ondansetron and 19 ( 29 % ) of those given prochlorperazine were treatment failures , experiencing more than five emetic episodes on their worst day during the study . Both drugs were well tolerated , although constipation was seen more commonly with ondansetron OBJECTIVE To compare the efficacy and side effects of ondansetron with those of high-dose metoclopramide in treating acute and delayed cisplatin-induced nausea and vomiting .  DESIGN R and omized , double-blind , crossover trial . SETTING Conducted at two university hospitals , a cancer institute , and six community hospitals . PATIENTS Of 125 patients , 95 were evaluable for the acute phase and 79 for the delayed phase . Major reasons for not being evaluable were no second course ( 14 patients ) , protocol violation ( 5 patients ) , and change in cisplatin dose ( 3 patients ) for the acute phase , and rescue medication on day 1 ( 7 patients ) , protocol violation ( 3 patients ) , and inadequate data ( 4 patients ) for the delayed phase . INTERVENTIONS All patients received cisplatin , 50 to 100 mg/m2 body surface area ( median , 75 mg/m2 ) ; none had previously received chemotherapy .  Thirty minutes before the cisplatin administration , ondansetron was given intravenously over 15 minutes , at a loading dose of 8 mg followed by a continuous infusion of 1 mg/h for 24 hours . Metoclopramide was given at a loading dose of 3 mg/kg body weight , followed by a continuous infusion for 8 hours ( 4 mg/kg ) . For the delayed phase ( days 2 through 6 ) , the first oral dose was given as soon as the infusion was completed ; the oral dose consisted of either metoclopramide , 20 mg three times daily , or ondansetron , 8 mg three times daily for another 5 days . MEASUREMENTS AND MAIN RESULTS In the acute phase , a major or complete response was seen in 72 % of the ondansetron-treated and 41 % of the metoclopramide-treated patients ( P less than 0.001 ) . Nausea was significantly better controlled among the ondansetron-treated patients ( P = 0.04 ) . In the delayed phase , no statistically significant difference was seen between ondansetron- and metoclopramide-treated patients . Nausea was significantly better controlled with metoclopramide ( P = 0.016 ) . CONCLUSIONS Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting . In the delayed phase , the results of both drugs were disappointing , although metoclopramide 's effect on delayed nausea was superior . Patients preferred ondansetron The majority of patients receiving cisplatin at a dose of 120 mg/m2 experience delayed nausea and vomiting occurring between 24 and 120 hours after chemotherapy administration . Ninety-one patients who were receiving cisplatin ( 120 mg/m2 ) as initial chemotherapy were entered into this double-blind trial . All patients received intravenous ( IV ) metoclopramide , dexamethasone , and lorazepam for the control of acute emesis during the period from 0 to 24 hours after cisplatin . Patients were then r and omized to one of three treatment regimens : placebo ; oral dexamethasone , 8 mg twice daily for two days , then 4 mg twice daily for two days ; or the combination of oral metoclopramide , 0.5 mg/kg four times daily for four days , plus oral dexamethasone administered as above . Forty-eight percent of individuals who received the two-drug combination of metoclopramide plus dexamethasone experienced delayed vomiting as opposed to 65 % who were administered dexamethasone alone and 89 % who received placebo ( P = .006 ) . Scores assessing the severity of delayed nausea and vomiting were consistently worse in individuals receiving placebo . The incidences of sleepiness , restlessness , heartburn , hiccoughs , loose bowel movements , insomnia , and acute dystonic reactions did not differ significantly among the three regimens and were mild and self-limited . The two-drug combination of oral metoclopramide plus dexamethasone is well tolerated , safe , and more effective than dexamethasone alone or placebo in controlling delayed vomiting following cisplatin A prospect i ve trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron ( TRO ) , a 5-HT3 receptor antagonist , in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide ( MET ) .  Nausea was grade d 0 ( absent ) , 1 ( mild ) , 2 ( moderate ) and 3 ( severe ) . Nausea requiring anti-emetics ( > or = grade 2 ) was present in 64 % of the patients . MET was able to control nausea ( < or = grade 1 ) in 26 of 58 patients ( 45 % ) who developed > or = grade 2 nausea during radiation treatment ( 2 patients vomiting without nausea included ) . 34 patients required TRO , and 31 experienced immediate relief . However , nausea ( > or = grade 2 ) recurred in 7 patients from 1 to 3 weeks after starting TRO . Sex , age , field type and field size ( cm2 ) did not influence the incidence and severity of nausea and vomiting . Only 24/88 patients vomited after starting radiotherapy . MET helped to eliminate emesis in one third of these patients . TRO helped to control vomiting in 73 % of the salvaged patients . Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases BACKGROUND Although all first-generation 5-HT(3 ) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting ( CINV ) , effective prevention of delayed CINV has not yet been achieved . This study compared the efficacy and tolerability of palonosetron , a novel , second-generation 5-HT(3 ) receptor antagonist , with ondansetron . PATIENTS AND METHODS In this multicenter , r and omized , double-blind , stratified , phase III study , 570 adult cancer patients were r and omized to receive a single i.v . dose of palonosetron 0.25 mg , palonosetron 0.75 mg or ondansetron 32 mg , each administered 30 min before initiation of moderately emetogenic chemotherapy . The primary end point was the proportion of patients with no emetic episodes and no rescue medication [ complete response ( CR ) ] during the 24 h after chemotherapy administration ( acute period ) . Secondary end points included efficacy in treatment of delayed CINV ( < /=5 days post-chemotherapy ) and overall tolerability . RESULTS 563 patients were evaluable for efficacy .  CR rates were significantly higher ( P < 0.01 ) for palonosetron 0.25 mg than ondansetron during the acute ( 0 - 24 h ) ( 81.0 % versus 68.6 % , respectively ) , delayed ( 24 - 120 h ) ( 74.1 % versus 55.1 % ) and overall ( 0 - 120 h ) ( 69.3 % versus 50.3 % ) periods . CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals . Both treatments were well tolerated . CONCLUSIONS A single i.v . dose of palonosetron 0.25 mg was significantly superior to i.v . ondansetron 32 mg in the prevention of acute and delayed CINV To compare ondansetron ( GR 38032F ) , a 5-hydroxytryptamine3-receptor antagonist , with metoclopramide in the prophylaxis of acute cisplatin-induced emesis , we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin ( 80 to 100 mg per square meter of body-surface area ) for treatment of cancer . None had received chemotherapy before this trial . Among the 76 patients who satisfactorily completed both parts of the study , complete or nearly complete control of emesis ( i.e. , no episodes of emesis occurred , or only one or two ) was achieved in 57 of 76 treatments ( 75 percent ) with ondansetron and in 32 of 76 treatments ( 42 percent ) with metoclopramide ( P less than 0.001 ) . Ondansetron was also more effective in controlling acute nausea , as assessed with a visual-analogue scale ( P = 0.019 ) or a grade d scale ( P = 0.024 ) . There was a significant preference among patients for ondansetron ( 55 vs. 26 percent ; P = 0.006 ) . Dystonic reactions were observed during three treatments with metoclopramide ; both agents were otherwise well tolerated . We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting , and that this suggests that serotonin is an important mediator of this side effect The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy . Granisetron controlled the onset of vomiting in 17 of 23 patients ( 73.9 % ) who were given 40 microg/kg of granisetron , while 8 of 21 patients ( 38.1 % ) were free of vomiting in the 20 microg/kg group . The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose . No safety problems were associated with either dose . The 40 microg/kg dose of granisetron appears to be more optimal Aprepitant is a neurokinin1 receptor antagonist that , in combination with a corticosteroid and a 5‐hydroxytryptamine3 receptor antagonist , has been shown to be very effective in the prevention of chemotherapy‐induced nausea and vomiting . At doses used for the management of chemotherapy‐induced nausea and vomiting , aprepitant is a moderate inhibitor of cytochrome P4503A4 and may be used in conjunction with corticosteroids such as dexamethasone and methylprednisolone , which are substrates of cytochrome P4503A4 . The effects of aprepitant on the these 2 corticosteroids were evaluated BACKGROUND Serotonin-receptor antagonists seem to be as effective as corticosteroids in preventing emesis induced by moderately emetogenic antineoplastic agents . We compared the antiemetic effect of a combination of granisetron and dexamethasone with that of granisetron or dexamethasone administered alone . METHODS From December 1992 to January 1994 , 482 consecutive patients who were to receive moderately emetogenic chemotherapy for the first time ( 600 to 1000 mg of cyclophosphamide per square meter of body-surface area , > or = 50 mg of doxorubicin per square meter , > or = 75 mg of epirubicin per square meter , or > or = 300 mg of carboplatin per square meter , alone or in some combination )  were enrolled in a double-blind , r and omized , multi-center study evaluating the efficacy and toxicity of three antiemetic regimens . The following antiemetic regimens were used : 8 mg of dexamethasone given intravenously before chemotherapy plus 4 mg given orally immediately before chemotherapy and then every six hours for a total of four doses , 3 mg of granisetron given intravenously before chemotherapy , or a combination of granisetron and dexamethasone given in the doses used for the single-drug regimens . RESULTS We evaluated 408 patients ( 136 receiving dexamethasone , 137 receiving granisetron , and 135 receiving both drugs ) . In the first 24 hours after chemotherapy , complete protection from vomiting and complete protection from nausea were achieved in 70.6 and 55.1 percent , respectively , of the patients receiving dexamethasone , in 72.3 and 48.2 percent of those receiving granisetron , and in 92.6 and 71.9 percent of those receiving granisetron combined with dexamethasone ( P < 0.001 for all comparisons ) . Patients who received granisetron alone had less protection from delayed vomiting and nausea than those who received dexamethasone alone or the two drugs combined . All the regimens were equally well tolerated . CONCLUSION Granisetron combined with dexamethasone was the most effective regimen for the prevention of emesis induced by moderately emetogenic chemotherapy We evaluated the efficacy and safety of oral ondansetron , a selective antagonist of 5-HT3 receptors , for the treatment of nausea and vomiting associated with  cyclophosphamide-based chemotherapy ( > 500 mg/m2 ) . In this trial 324 chemotherapy-naive cancer patients , mostly females with breast cancer , were r and omized to receive either placebo or ondansetron 1 mg , 4 mg , or 8 mg three times per day for 3 days . There were no differences in the doses of cyclophosphamide , doxorubicin , and methotrexate between the study groups . All ondansetron dose groups were superior to the placebo control group ( p < .001 ) for all measured efficacy parameters ( complete response , number of emetic episodes , therapeutic failures , need of rescue antiemetics ) . No emetic episodes were reported by 9 ( 12 % ) , 29 ( 37 % ) , 48 ( 64 % ) , and 47 ( 66 % ) of the placebo patients and the 1-mg , 4-mg , and 8-mg dose of ondansetron patients , respectively . Nausea was reduced and food intake was improved for all the ondansetron groups . A more severe emetic response was observed in patients receiving cyclophosphamide and doxorubicin combination chemotherapy . In this subgroup of patients . 66 % , 38 % . 25 % , and 16 % of the placebo group and 1-mg , 4-mg , and 8-mg ondansetron patients , respectively , required rescue anti-emetics . No significant toxic effects were observed in this study . A higher incidence of headaches and gastrointestinal complaints ( constipation , abdominal pain ) were observed in the three ondansetron groups . In conclusion , oral ondansetron is an effective and well-tolerated antiemetic treatment in the management of cancer patients receiving ambulatory cyclophosphamide-based chemotherapy .  These results support the view that serotonin and 5-HT3 receptors play an important role in cyclophosphamide-induced nausea and vomiting This prospect i ve study was design ed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia ( ALL ) undergoing moderately emetogenic cyclophosphamide-based chemotherapy .  The costs for both treatments are also examined . A total of 33 children ( mean age : 7.8 + /- 4.9 year ) were studied during 66  chemotherapy cycles . Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally . There was no significant difference between the 2 treatments in terms of overall efficacy ( McNemar 's chi-square test ) . Twenty of 33 patients ( 60.6 % ) receiving granisetron and 15 of 33 patients ( 45.5 % ) receiving ondansetron experienced no emesis 24 h after chemotherapy ( p = .227 ) . Boys experienced greater rates of vomiting than did girls despite antiemetic treatment ; however , no apparent reason for the gender discrepancy was noted . Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy . It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective We compared the efficacy and safety of ondansetron ( GR 38032F ) , a selective antagonist of serotonin S3 receptors , with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer . The patients received either three intravenous doses of ondansetron ( 0.15 mg per kilogram of body weight ) or normal saline ( placebo ) at four-hour intervals , beginning 30 minutes before the administration of cisplatin .  Nausea and vomiting were markedly diminished in the group given ondansetron . The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group ( P less than 0.001 ) ; the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group ( P less than 0.001 ) ; the mean ( + /- SEM ) number of regurgitations or dry heaves per episode was 3.2 + /- 0.5 in the placebo group and 1.17 + /- 0.1 in the ondansetron group ( P less than 0.001 ) . None of the 14 patients given ondansetron , but 12 of 14 given placebo , required treatment with antiemetic-rescue agents  for the control of nausea and vomiting . There were no adverse effects attributable to ondansetron . The urinary excretion of 5-hydroxyindoleacetic acid , the main metabolite of serotonin , was increased in all patients two to six hours after they received cisplatin chemotherapy , and the increases paralleled the episodes of emesis . We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment . We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells , and that ondansetron acts by blocking S3 receptors for serotonin Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy . In vitro , aprepitant is a moderate inhibitor of the CYP3A4 enzyme , which is involved in the clearance of several chemotherapeutic agents . In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel , a chemotherapeutic agent that is primarily metabolized by CYP3A4 . Methods A total of 11 cancer patients ( 4 male , 7 female , aged 50–68 years ) were enrolled in this multicenter , r and omized , open-label , two-period , crossover study . Patients received a single infusion of docetaxel monotherapy , 60–100 mg/m2 , on two occasions at least 3 weeks apart . During one of the cycles ( treatment A ) , patients received docetaxel alone . During the alternate cycle ( treatment B ) , they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion ( day 1 ) , and a single oral dose of aprepitant 80 mg on days 2 and 3 . The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion . Blood counts were monitored on days 1 , 4 , 7 , and 14 . Results Ten patients completed the study . Concomitant administration of aprepitant did not cause any statistically or clinical ly significant changes in docetaxel pharmacokinetics . Values for docetaxel alone ( treatment A ) versus docetaxel with aprepitant ( treatment B ) were as follows : geometric mean AUC0–last was 3.26 vs 3.17 μg h/ml ( P>0.25 ; ratio B/A 0.97 ) ; geometric mean AUC0–∞ 3.51 vs 3.39 μg h/ml ( P>0.25 ; ratio B/A 0.96 ) ; geometric mean Cmax was 3.53 vs 3.37 μg/ml ( P>0.25 ; ratio B/A 0.95 ) ; and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m2 ( P>0.25 ; ratio B/A 1.04 ) . The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles ; the median absolute neutrophil count nadirs were 681/mm3 during treatment with docetaxel alone and 975/mm3 during aprepitant coadministration . Conclusions Aprepitant had no clinical ly significant effect on either the pharmacokinetics or toxicity of st and ard doses of docetaxel in cancer patients . Aprepitant at clinical ly recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4 Background . A single‐institution , r and omized open trial was prospect ively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin‐based chemotherapy . The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy BACKGROUND Although ondansetron was found to be effective as an antiemetic in numerous clinical trials of highly emetogenic combination-chemotherapy regimens that included cisplatin , its role in milder emetogenic regimens has not been fully defined . To address its use with a widely used but less emetogenic regimen , we performed a double-blind , r and omized clinical trial comparing ondansetron with dexamethasone and metoclopramide in patients with breast cancer receiving chemotherapy with cyclophosphamide , methotrexate , and fluorouracil . METHODS A total of 165 women with breast cancer from 14 Canadian centers who were about to receive this chemotherapy for the first time were r and omly assigned to receive either ondansetron ( n = 85 ) or dexamethasone plus metoclopramide ( n = 80 ) , a widely used , st and ard antiemetic regimen . The patients recorded the incidence of nausea , emesis , and other side effects in diaries , and these data were compared in the two groups . RESULTS The patients who received dexamethasone and metoclopramide had significantly less nausea during the first 24 hours after chemotherapy was begun . Otherwise , there were no statistically significant differences in efficacy between the regimens . The incidence of drowsiness and increased appetite was higher in the group given dexamethasone and metoclopramide . CONCLUSIONS For women with breast cancer who are being treated with cyclophosphamide , methotrexate , and fluorouracil , the efficacy of dexamethasone and metoclopramide in controlling nausea and vomiting equaled or exceeded that of ondansetron The neurokinin‐1 antagonist aprepitant ( EMEND ™ ; Merck Research Laboratories , West Point , PA ) has been shown to reduce chemotherapy‐induced nausea and vomiting when it is given with a 5‐hydroxytryptamine‐3 receptor antagonist and dexamethasone . The current study sought to define the most appropriate dose regimen of oral aprepitant A double-blind double-dummy , comparative study was carried out in 30 patients receiving highly emetogenic fast dose rate , single fraction total body irradiation prior to bone marrow transplantation . Patients were r and omised into one of two groups , receiving either granisetron , a specific 5-HT3 antagonist or a combination of metoclopramide , dexamethasone phosphate and lorazepam to assess the comparative efficacy of the two regimens in the control of irradiation-induced nausea and vomiting . After 24 h eight patient ( 53 % ) treated with granisetron showed a complete response compared with two patients ( 13 % ) in the comparator group . The control of vomiting by granisetron , over both 24 h and 7-day periods ( P = 0.001 and P = 0.004 ) , was significantly better than that seen with the comparator and required significantly fewer rescue doses . The safety profiles in the two groups appeared similar , with the exception that granisetron produced less drowsiness than the comparator PURPOSE This is the first study in which the NK(1)-receptor antagonist , aprepitant ( APR ) , was evaluated for the prevention of chemotherapy-induced nausea and vomiting ( CINV ) with moderately emetogenic chemotherapy . PATIENTS AND METHODS Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide + /- doxorubicin or epirubicin .  Patients were r and omly assigned to either an aprepitant regimen ( day 1 , APR 125 mg , ondansetron ( OND ) 8 mg , and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , APR 80 qd ) [ DOSAGE ERROR CORRECTED ] or a control regimen ( day 1 , OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , OND 8 mg bid ) . Data on nausea , vomiting , and use of rescue medication were collected with a self-report diary . The primary efficacy end point was the proportion of patients with complete response , defined as no vomiting and no use of rescue therapy , during 120 hours after initiation of chemotherapy in cycle 1 . The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis question naire . RESULTS Of 866 patients r and omized , 857 patients ( 99 % ) were assessable .  Overall complete response was greater with the aprepitant regimen than with the control regimen ( 50.8 % v 42.5 % ; P = .015 ) . More patients in the aprepitant group reported minimal or no impact of CINV on daily life ( 63.5 % v 55.6 % ; P = .019 ) . Both treatments were generally well tolerated . CONCLUSION The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide PURPOSE The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation ; the effects of specific antiemetics especially ondansetron , a 5-hydroxytryptamine receptor antagonist , and to determine the relationship between radiation-induced emesis and serotonin ( 5-hydroxytryptamine ) through its active metabolite , 5-hydroxyindoleacetic acid ( 5-HIAA ) . METHODS AND MATERIAL S Forty-one patients received 53 hemibody treatments of 5 - 8 Gy following intravenous hydration .  The patients were divided into three groups according to prehemibody irradiation treatment : Group A : no pretreatment antiemetics , 30 patients ; Group B : nonondansetron antiemetics ( metoclopramide , dexamethasone , prochlorperazine ) , ten patients ; and Group C : ondansetron , 13 patients . The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA ( ng/ug creatinine ) . RESULTS The incidence of radiation-induced emesis was 82 % ( 14/17 ) following upper/mid hemibody irradiation and 15 % ( 2/11 ) following lower hemibody irradiation in Group A ; 50 % ( 3/6 ) and 25 % ( 1/4 ) following upper/mid and lower hemibody irradiation respectively , in Group B ; and 0 % ( 0/13 ) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different ( p < 0.001 ) between the patients of Group A and C who received upper/mid hemibody irradiation . The percent change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C ( p < 0.002 ) . The degree of change following lower hemibody irradiation ( 15 % incidence of emesis ) in Group A was lower than upper/mid hemibody irradiation of the same group . CONCLUSION The higher incidence of radiation-induced emesis following upper and mid hemibody irradiation in antiemetic naive patients compared to the incidence following lower hemibody irradiation suggests that the critical organ responsible for radiation sickness is in the abdomen . The control of emesis by ondansetron , a 5-HT3 receptor antagonist , attests to the efficacy of ondansetron in radiation-induced emesis and suggests a role for serotonin in mediating radiation-induced emesis . Finally , the parallel changes in 5-HIAA and the incidence of emesis provides additional evidence for a more direct role for serotonin in radiation-induced emesis BACKGROUND Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy . PROCEDURE An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy . Patients received dolasetron in single intravenous doses of 0.6 ( n = 10 ) , 1.2 ( n = 12 ) , 1.8 ( n = 12 ) , or 2.4 ( n = 12 ) mg/kg 30 min before receiving emetogenic chemotherapy .  Pharmacokinetic parameters were evaluated at each dose level and efficacy was evaluated over the first 24 hr following the administration of dolasetron . RESULTS A complete response was achieved in 10 % of patients given 0.6 mg/kg , 25 % of patients given 1 . 2 mg/kg , 67 % of patients given 1.8 mg/kg , and 33 % of patients given 2.4 mg/kg . Peak plasma concentrations ( Cmax ) were observed between 0 . 33 and 0.75 hr following dolasetron infusion . Cmax and area under plasma concentration-time ( AUC ) increased with larger doses of dolasetron , while terminal disposition half-life ( t1/2 ) and apparent clearance ( Clapp ) were not significantly changed with respect to dose . For 1.8-mg/kg dolasetron , the t1/2 was 4.98 hr and the maximum plasma concentration ( tmax ) 0.47 hr . Adverse events were mild to moderate . No serious events occurred . Conclusions . This study suggests that a single intravenous dose of 1.8 mg/kg is the optimum single intravenous dose for controlling chemotherapy-induced emesis in pediatric patients Aprepitant is a novel neurokinin 1 ( NK1 ) antagonist that has been shown to improve control of chemotherapy‐induced nausea and vomiting ( CINV ) when added to a st and ard antiemetic regimen of a 5‐hydroxytriptamine‐3 antagonist plus a corticosteroid . The authors sought to evaluate further the efficacy and tolerability of aprepitant plus st and ard therapy in a large clinical trial PURPOSE In early clinical trials with patients receiving highly emetogenic chemotherapy , the neurokinin antagonist aprepitant significantly enhanced the efficacy of a st and ard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid . This multicenter , r and omized , double-blind , placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus st and ard therapy in the prevention of chemotherapy-induced nausea and vomiting ( CINV ) . PATIENTS AND METHODS Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either st and ard therapy ( ondansetron and dexamethasone on day 1 ; dexamethasone on days 2 to 4 ) or an aprepitant regimen ( aprepitant plus ondansetron and dexamethasone on day 1 ; aprepitant and dexamethasone on days 2 to 3 ; dexamethasone on day 4 ) . Patients recorded nausea and vomiting episodes in a diary . The primary end point was complete response ( no emesis and no rescue therapy ) on days 1 to 5 postcisplatin , analyzed by a modified intent-to-treat approach . Treatment comparisons were made using logistic regression models . Tolerability was assessed by reported adverse events and physical and laboratory assessment s. RESULTS The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group ( 72.7 % [ n = 260 ] v 52.3 % in the st and ard therapy group [ n = 260 ] ) , as were the percentages on day 1 , and especially on days 2 to 5 ( P < .001 for all three comparisons ) . CONCLUSION Compared with st and ard dual therapy , addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy Factors related to the prevalence , prediction , and course of anticipatory nausea ( AN ) in women ( n = 77 ) receiving adjuvant chemotherapy for breast cancer were examined . Using a prospect i ve longitudinal research design , patients were interviewed both before and after each chemotherapy infusion . Fifty‐seven percent of the patients developed AN . These patients were characterized by more severe gastrointestinal side effects following the initial infusion and greater expectations for experiencing chemotherapy‐related nausea . A more rapid development of AN was related to a history of experiencing nausea across a greater variety of situations , higher IV drug doses , and less infusion‐related anxiety at the initial infusion . Although AN occurred intermittently across treatment sessions , severity was constant . Results provided strong support for the hypothesis that classical conditioning processes are instrumental in AN acquisition . The role of anxiety in the development of AN is considered as are clinical implication s for the prevention of AN and recommendations for future research Cisplatin may evoke both an acute emetic response during the first 24 hours following treatment and a less well-recognized syndrome of delayed emesis . While delayed emesis is usually less severe in terms of frequency of vomiting episodes , the problem continues to result in significant morbidity . In comparison with acute emesis , the exact pathogenesis of the delayed emesis syndrome remains unclear . Although a combination of oral metoclopramide and dexamethasone is effective in many patients in preventing delayed emesis , almost 50 % continue to experience at least one emetic episode when treated with this regimen . A phase III multicenter study has evaluated oral ondansetron versus placebo in the prevention of the  delayed-emesis syndrome in 50 patients during days 2 through 5 following high-dose cisplatin administration . Although the daily rates of complete emetic control , failure , and control of nausea favor ondansetron , this trial is statistically inconclusive in establishing efficacy of ondansetron as a single agent in the prevention of delayed emesis .  Ondansetron was well tolerated in the dose and schedule used The nausea and vomiting experienced by one in four cancer patients in anticipation of chemotherapy is probably a learned response to treatment . To determine whether behavioral approaches for altering learned responses might be useful treatments for these symptoms , we compared the effects of " systematic desensitization " ( a behavioral treatment in which relaxation is learned as a response to situations in which patients have had anticipatory nausea and vomiting ) with those of counseling and of no treatment .  Sixty ambulatory cancer patients with anticipatory nausea and vomiting before their third and fourth chemotherapy treatments were r and omized equally to the three groups . Significantly more patients receiving desensitization reported no anticipatory nausea before their fifth and sixth chemotherapy treatments than patients given counseling ( P less than 0.05 ) or no treatment ( P less than 0.01 ) . Desensitized patients also reported significantly less severe anticipatory nausea ( P less than 0.01 ) and vomiting ( P less than 0.05 ) and a shorter duration of anticipatory nausea ( P less than 0.01 ) . We conclude that systematic desensitization appears to have an antiemetic effect in cancer patients who receive chemotherapy , and may be useful in the management of these problems To prevent delayed emesis induced by cisplatin ( mean dose 90 mg/m2 ) , 120 consecutive patients were r and omized to receive , in a 7-day crossover design , oral metoclopramide ( 20 mg q.i.d . ) , dexamethasone ( 1 mg q.i.d . ) or placebo ( two tablets q.i.d . ) starting 24 hours after the end of chemotherapy .  Complete protection from nausea , but not from vomiting . was significantly increased by both dexamethasone and metoclopramide with respect to placebo . Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin , female gender , and highest cisplatin doses . Tolerability of both drugs was good . Larger and r and omized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin BACKGROUND Although usually a problem of cisplatin-based chemotherapy , delayed emesis can cause severe distress in patients treated with cyclophosphamide . Dexamethasone has been shown to be effective in the control of cisplatin-induced delayed emesis , but its role against the delayed problem in patients treated with cyclophosphamide  has not been demonstrated . Our study was conducted to evaluate the effect of dexamethasone in delayed emesis induced by cyclophosphamide . PATIENTS AND METHODS Ninety-eight patients were given i.v . granisetron and i.v . dexamethasone before chemotherapy , and r and omised to receive either oral dexamethasone 4 mg twice daily as maintenance or no maintenance . RESULTS Ninety-four patients were evaluable . Of those given maintenance oral dexamethasone , 57 % had complete and 30 % had major control of delayed emesis , versus 33 % and 15 % , respectively , of patients who did not receive maintenance . Side effects are mainly constipation and headache . CONCLUSION The results shows that oral dexamethasone is an effective agent against cyclophosphamide-induced delayed emesis Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer . We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation ( TBI ) 12 Gy/3 days as conditioning for bone marrow transplantation .  Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy . Twenty-two of the 25 patients ( 88 % ) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12 % experienced three to five emetic events during their worst 24-h period . Eleven patients ( 44 % ) had complete control with no vomiting at all . Of 75 ' patient days ' , 52 ( 69 % ) were without any emesis , 20 ( 27 % ) were associated with one to two and only three ( 4 % ) with three to five emetic episodes . Headache occurred in four patients ( 16 % ) . No other significant adverse effects were seen , in particular no extrapyramidal reactions due to ondansetron . Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI The development of anticipatory nausea in cancer chemotherapy typically has been viewed in terms of a respondent learning model . Firm support for this etiological model has been precluded by use of retrospective research design s , however . The present study employed a prospect i ve design to identify patient and treatment-related variables characteristic of patients who subsequently develop anticipatory nausea . Seventy-one chemotherapy out patients were interviewed before and after each chemotherapy infusion during their first 6 months of treatment . Hierarchical multiple regression analysis revealed that patients who developed anticipatory nausea were characterized by more severe posttreatment nausea , more time-consuming treatment infusions , and greater state anxiety relative to patients without anticipatory nausea . In general , results supported a respondent learning conceptualization of the development of anticipatory nausea . Clinical implication s of these findings for the prevention of anticipatory nausea are suggested One hundred and seventy-five patients selected at r and om were prospect ively studied . All patients were assessed at least after the first cycle of treatment by a self-report question naire which covered the occurrence of nausea and vomiting 24 before chemotherapy , as well as information regarding 22 clinical parameters . Forty-six ( 26 % ) patients developed anticipatory nausea . ' Intolerable ' posttreatment vomiting and age under 45 were statistically significant parameters ( p less than 0.05 ) in the multivariate analysis . Twenty-one ( 12 % ) of the 175 patients experienced anticipatory vomiting . Three variables , age under 45 , ' intolerable ' posttreatment vomiting and more than three cycles of treatment were found to be significant ( p less than 0.05 ) . The relative risk of developing anticipatory nausea and vomiting according to combination of significant clinical predictors in the multivariate analysis is proposed . Therefore recognition of these clinical predictors may serve as a marker for patients with high risk of presenting anticipatory nausea and vomiting , who may benefit from prophylactic behavioral approaches Two large r and omized , double-blind , placebo-controlled studies with an appropriate study design have been conducted to fully evaluate the efficacy of ondansetron in the control of  cisplatin-induced delayed emesis .  These studies show that ondansetron and particularly ondansetron plus dexamethasone have moderate efficacy in the control of  cisplatin-induced delayed emesis and nausea . The benefit of ondansetron , with or without dexamethasone , may be greatest in patients with incomplete control of acute emesis .  The efficacy of ondansetron in this setting compared to its greater efficacy during the acute phase of emesis induced by cisplatin and the more prolonged phases of acute emesis induced by cyclophosphamide and carboplatin indicates that non-5-HT3-mediated emetic mechanisms maybe are relatively more important in the delayed phase of emesis following cisplatin
target: 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 .
background: PURPOSE To up date the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology .