***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 
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    Input: BACKGROUND High dose methotrexate ( HD-MTX ) , used in the treatment of children with acute lymphoblastic leukemia ( ALL ) , is moderately emetogenic . First generation 5-HT(3 ) receptor antagonists are effective prophylactic agents but require multiple administrations . Palonosetron has a half life of 36 - 42 hours and has higher affinity and selectivity to the 5-HT(3 ) receptor . Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3 ) receptor antagonists . The purpose of this study was to examine the effect of a single dose of palonosetron ( 5 µg/kg ) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX , 5 g/m(2 ) . PROCEDURE Between January 2010 and December 2010 , 138 courses , originating from 53 children , were included from four Danish Childhood Cancer Centers . Information regarding emetic episodes , rescue therapy , and nausea were recorded prospect ively on question naires . RESULTS Complete response ( no emesis and no rescue therapy ) was achieved in 84.1 % of courses during the acute ( 0 - 24 hours post-chemotherapy ) and in 60.1 % during the delayed phase ( 24 - 66 hours post-chemotherapy ) . 92.0 % of courses were free of emesis during the acute , and 86.2 % were free of emesis during the delayed phase . 76.8 % of courses were free of nausea during the acute , and 78.3 % were free of nausea during the delayed phase . CONCLUSIONS A single dose of palonosetron -- without concomitant corticosteroid -- was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD-MTX Palonosetron is a potent , selective 5-HT(3 ) receptor antagonist effective in the prevention of acute and delayed chemotherapy-induced nausea and vomiting . In practice , 5-HT(3 ) receptor antagonists , including palonosetron , are often coadministered with dexamethasone over approximately 15 minutes , although the approval of palonosetron was based on administration as a 30-second infusion . This open-label , r and omized , 2-way crossover trial compared the pharmacokinetics and safety of palonosetron 0.25 mg administered as a 15-minute 50-mL intravenous infusion with a 30-second 5-mL infusion . Aside from an anticipated 40 % decrease in maximum plasma concentration after a 15-minute infusion , the pharmacokinetics of palonosetron  ( including area under the plasma concentration-time curve [ AUC ] , plasma elimination half-life , total body clearance , and apparent volume of distribution at steady state ) were similar for both treatments . Both treatments were well tolerated , with no significant changes in vital signs or electrocardiograms .  Palonosetron infused over 15 minutes is well tolerated , with an AUC(0-infinity ) equivalent to a 30-second infusion Chemotherapy-induced nausea and vomiting is ranked among the worst side effects of chemotherapy . NEPA is an oral fixed-dose combination antiemetic under development , consisting of netupitant 300 mg , a highly selective NK1 receptor antagonist ( RA ) , and palonosetron 0.5 mg , a pharmacologically and clinical ly distinct 5-HT3 RA . Although palonosetron is not associated with relevant ECG effects , this study evaluated cardiovascular safety of netupitant in combination with palonosetron , as well as its tolerability . This r and omised , placebo- and positively controlled study in 197 subjects included 4 treatment groups : placebo , 200 mg netupitant + 0.5 mg palonosetron ( NEPA200/0.5 ) , 600 mg netupitant + 1.5 mg palonosetron ( NEPA600/1.5 , a supratherapeutic dose ) , and 400 mg moxifloxacin . Assessment s included a 24-h baseline ECG recording , followed by a single dose of treatment and ECG measurements for 2 days . Mean placebo-corrected time-averaged changes from baseline were similar in NEPA200/0.5 and NEPA600/1.5 groups primarily for individually heart rate-corrected QT interval ( QTcI : + 4.7 and + 3.6 ms , respectively ) and for heart rate ( HR : –3.3 bpm and –3.0 bpm ) , PR interval ( –0.4 ms and 0.2 ms ) , and QRS interval ( 1 ms and 0.5 ms ) . The time-matched analysis showed no upper confidence interval > 10 ms , with no suggestion of a QTc effect by pharmacokinetic-pharmacodynamic modeling for parent/metabolites . Moxifloxacin showed the expected placebo-corrected change from baseline ( + 8.4 ms time average ) and the expected profile to establish assay sensitivity . No new morphologic changes of clinical relevance were observed . Treatment-related adverse events were comparable among groups . This study showed that NEPA treatments produced no significant effects on QTcI , HR , PR interval , QRS interval , and cardiac morphology relative to placebo , even at supratherapeutic doses BACKGROUND Although currently available 5-hydroxytryptamine type 3 receptor ( 5-HT3 ) antagonists are effective , not all patients receiving these agents achieve adequate control of chemotherapy-induced nausea and vomiting ( CINV ) . Palonosetron , a potent and highly selective 5-HT3 antagonist with a strong affinity for 5-HT3 and a prolonged plasma elimination half-life , may provide a longer duration of action than other approved agents . PATIENTS AND METHODS One hundred and sixty-one patients were r and omly assigned to receive a single intravenous bolus dose of palonosetron ( 0.3 , 1 , 3 , 10 , 30 or 90 microg/kg ) before administration of highly emetogenic chemotherapy , with no pretreatment with corticosteroids . RESULTS The four highest doses of palonosetron were similarly effective during the first 24 h , producing clearly higher complete response ( CR ) ( no emesis , no rescue medication ) rates in the 3 , 10 , 30 and 90 microg/kg groups ( 46 % , 40 % , 50 % and 46 % , respectively ) than in the 0.3 - 1 microg/kg group ( 24 % ) of evaluable patients ( n = 148 ) . The 3 microg/kg dose was identified as the lowest effective dose . A single dose of palonosetron showed prolonged efficacy in preventing delayed emesis , with approximately one-third of patients who received palonosetron 10 or 30 microg/kg maintaining a CR throughout the 7-day period following chemotherapy administration . Dose-proportional increases in pharmacokinetic parameters and a long plasma half-life ( 43.7 - 128 h ) were observed . Palonosetron was well-tolerated , with no dose-response effect evident for the incidence or intensity of adverse events . CONCLUSIONS Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy , with 3 and 10 microg/kg identified as the lowest effective palonosetron doses This study evaluated the safety and pharmacokinetics of consecutive multiple-day dosing of palonosetron .  Sixteen healthy subjects received an intravenous bolus dose of  palonosetron 0.25 mg ( n = 12 ) or placebo ( n = 4 ) daily for 3 consecutive days . Safety was evaluated throughout the study . Serial plasma sample s were collected on days 1 and 3 for pharmacokinetic determinations . Three days of dosing with palonosetron 0.25 mg was safe and well tolerated . There were no clinical ly significant changes from baseline in laboratory values , vital signs , physical examinations , or electrocardiogram intervals . Plasma palonosetron concentrations declined in a biphasic manner , measurable up to 168 hours after dosing on day 3 . Mean terminal phase elimination half-life after day 3 dosing was 42.8 hours . The 2.1-fold accumulation of  palonosetron in plasma following 3 daily doses was predictable based on elimination half-life of approximately 40 hours , and the maximum plasma concentration remained below the maximum plasma concentration previously observed after a single , well-tolerated 0.75 mg intravenous bolus dose of palonosetron BACKGROUND Chemotherapy-induced nausea and vomiting ( CINV ) in children is a major side effect despite the use of combination antiemetic drugs . OBJECTIVE To compare the efficacy and safety profile of palonosetron , a second-generation 5-hydroxytryptamine-3 ( 5-HT3 ) receptor antagonist , with ondansetron in the prevention of CINV in children . METHODS A prospect i ve , r and omized , crossover study was conducted in patients aged 2 - 18 years . 160 chemotherapy cycles , consisting of chemotherapy drugs with moderate- and high-emetogenic potential , were studied . The study group received a single dose of intravenous ( IV ) palonosetron 5 mcg/kg , and the st and ard group received IV ondansetron 5 mg/m2 every 8 hours while receiving chemotherapy . The patients were observed for vomiting , use of rescue antiemetic medications , and nausea from Day 1 0 - 72 hours after completion of each chemotherapy cycle . All adverse events during the study period were recorded . RESULTS The overall percentage of patients with complete response ( CR ) in the palonosetron and ondansetron groups were 60 % and 56.2 % , respectively ( 𝑃 = .631 ) . The CR rates in the palonosetron and ondansetron groups were 75 % and 70 % , respectively , in the acute phase ( 𝑃 = .479 ) , and 68.8 % and 65 % , respectively , in the delayed phase ( 𝑃 = .614 ) . There was no statistically significant difference in the CR rates cross both groups . CONCLUSION A single dose of palonosetron is noninferior to ondansetron in the prevention of CINV in children and can be considered as an alternative antiemetic drug . There was no significant difference in adverse effects between the palonosetron and ondansetron group ABSTRACT Background : Palonosetron is a second-generation 5-HT3 receptor antagonist with a prolonged duration of action and higher receptor binding affinity than first-generation agents ( ondansetron , granisetron , and dolasetron ) . Aprepitant is a selective antagonist of substance P/neurokinin 1 that augments the benefit of 5-HT3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting . Methods : This r and omized , open-label , two-way , crossover trial was design ed to evaluate the effect of oral aprepitant on the pharmacokinetics and safety of a single intravenous ( IV ) dose of palonosetron in 12 healthy subjects . Treatment A consisted of a single IV bolus dose of palonosetron 0.25 mg on day 1 . Treatment B added oral aprepitant 125 mg on day 1 ( 30 minutes prior to palonosetron ) and 80 mg on days 2 and 3 . Blood for pharmacokinetic evaluations was collected through 168 hours after palonosetron administration on days 1 and 15 ; safety was monitored through day 22 . Results : Mean plasma concentration-time plots  for palonosetron were virtually identical for palonosetron administered alone or with concomitant aprepitant . The ratio of geometric least-square mean values ( with : without aprepitant ) for Cmax was 98.6 % ( 90 % confidence interval [ CI ] : 61.8–157 % ) , and for AUC0–∞ the ratio was 101 % ( 90 % CI : 85.6–119 % ) . With and without aprepitant coadministration , respectively , mean plasma elimination half-life was 40 hours and 43 hours ( difference : –3.0 hours ; p = 0.348 ) , mean total body clearance was 130 mL/min and 136 mL/min ( difference : –5.6 mL/min ; p = 0.735 ) , and mean volume of distribution at steady-state was 410.9 L and 442.3 L ( difference : –31.4 L ; p = 0.463 ) . Palonosetron alone and the palonosetron/aprepitant regimen were well tolerated . Conclusion : These results indicate no significant differences in pharmacokinetic parameters for palonosetron between the two treatments , and suggest that palonosetron can be safely coadministered with aprepitant with no alterations in the expected safety profile and no dosage adjustment necessary Antiemetic treatment compliance is important to prevent chemotherapy‐induced nausea and vomiting , a feared chemotherapy side effect . NEPA , a new or 
    Output:
    
The recommendations were based on three systematic review s. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT3 antagonists recommended for children receiving highly emetogenic chemotherapy ( HEC ) and the recommendation of aprepitant for children 6 months of age or older receiving HEC .