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 .
PURPOSE To up date the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology .
Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients
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
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 .
PURPOSE To up date the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology .