Objectives: Current prophylactic interventions fail to completely eliminate postoperative nausea and vomiting (PONV) for a substantial number of patients. A new antiemetic (aprepitant) has been effective in preventing...Objectives: Current prophylactic interventions fail to completely eliminate postoperative nausea and vomiting (PONV) for a substantial number of patients. A new antiemetic (aprepitant) has been effective in preventing chemotherapy induced nausea and vomiting (CINV). We hypothesized that adding aprepitant to our current prophylactic regimen of dexamethasone and ondansetron would reduce the incidence of PONV in our elective hysterectomy population. Methods: 256 patients undergoing elective hysterectomy were enrolled in this prospective, randomized, double blinded, placebo controlled trial. Subjects received either oral aprepitant 40 mg or oral placebo 30 minutes prior to induction of standardized anesthesia. The primary outcome was vomiting within the first 24 hours after surgery. Postoperative nausea, vomiting, and use of rescue antiemetics were documented over a 24 h period. Additionally, adverse events, hospitalization days, and readmissions for PONV were compared. Results: There was a trend towards reduction of postoperative nausea and vomiting in the aprepitant group. Nausea and vomiting were noted for 24% and 17% of women in the aprepitant group versus 38% and 29% of women in the Placebo group, respectively. Supplemental antiemetic medication was used by 42% of women in the aprepitant group versus 60% of women in the Placebo group. No adverse events were substantially more common in the aprepitant group than the Placebo group. Conclusions: Preemptive use of aprepitant prior to elective hysterectomy may reduce the incidence of PONV and diminish the need for rescue antiemetics postoperatively. Further studies with larger power are needed to confirm the trends observed in this study.展开更多
Objective The aim of this study was to explore the clinical efficacy and toxicity of a combination aprepitant and palonosetron hydrochloride therapy in preventing chemotherapy-induced nausea and vomiting associated wi...Objective The aim of this study was to explore the clinical efficacy and toxicity of a combination aprepitant and palonosetron hydrochloride therapy in preventing chemotherapy-induced nausea and vomiting associated with a cisplatinum-based regimen in patients with lung cancer. Methods Sixty-eight patients with lung cancer were randomly assigned to receive either aprepitant plus palonosetron hydrochloride(group A, n = 38) or tropisetron(group B, n = 30). Acute(0–24 h) and delayed(2–5 d) emetic episodes, nausea, vomiting, constipation, and dizziness were compared between the two groups in the five days following cisplatinum-based chemotherapy.Results Group A had a higher complete control rate for both acute and delayed emetic episodes than Group B(36.8% vs. 13.3% and 31.6% vs. 13.3%, respectively; P < 0.05 for both). There was no significant difference in the constipation rate between the two groups. Conclusion Aprepitant combined with palonosetron hydrochloride is active and well tolerated in both acute and delayed emetic episodes in patients with lung cancer treated by a cisplatinum-based regimen.展开更多
Background:Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis.The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for ...Background:Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis.The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting(CINV)in patients with solid malignant tumors,determine risk factors and externally validate different personalized risk models for CINV.Methods:This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy.The primary endpoint was complete response(CR)during the overall phase(OP)with a non-inferiority margin of 10.0%.Logistic regression modelswere used to assess the risk factors ofCRand no nausea.To validate the personalized risk models,the accuracy of the risk scoring systems was determined by measuring the specificity,sensitivity and area under the receiver operating characteristic(ROC)curve(AUC),while the predictive accuracy of the nomogram was measured using concordance index(C-index).Results:A total of 720 patients were randomly assigned.CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group(78.1%vs.77.7%,P=0.765)with a between-group difference of 0.4%(95%CI,-5.7%to 6.6%).Female sex,higher cisplatin dose(≥70 mg/m2),no history of drinking and larger body surface area(BSA)were significantly associated with nausea.The AUC for the acute and delayed CINV risk indexes was 0.68(95%CI:0.66-0.71)and 0.66(95%CI:0.61-0.70),respectively,and the C-index for nomogram CINV prediction was 0.59(95%CI,0.54-0.64).Using appropriate cutoff points,the three models could stratify patients with high-or low-risk CINV.No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group(P<0.001).Conclusions:Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy.Female cancer patients without a history of alcohol consumption,with larger BSA and received high-dose cisplatin might be more vulnerable to CINV.Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.展开更多
The synthesis of two isomers of Aprepitant(APT)and three isomers of Fosaprepitant(FPT),crucial components for quality control in manufacturing,is described.Herein,three chiral centers in the isomers of Aprepitant are ...The synthesis of two isomers of Aprepitant(APT)and three isomers of Fosaprepitant(FPT),crucial components for quality control in manufacturing,is described.Herein,three chiral centers in the isomers of Aprepitant are established in high yield by induced crystallization and chiral reduction.Additionally,the isomers of Aprepitant are utilized to synthesize the isomers of Fosaprepitant with the same stereochemistry.All the target compounds were confrmed by elemental analyses,IR,NMR and MS data analysis.展开更多
文摘Objectives: Current prophylactic interventions fail to completely eliminate postoperative nausea and vomiting (PONV) for a substantial number of patients. A new antiemetic (aprepitant) has been effective in preventing chemotherapy induced nausea and vomiting (CINV). We hypothesized that adding aprepitant to our current prophylactic regimen of dexamethasone and ondansetron would reduce the incidence of PONV in our elective hysterectomy population. Methods: 256 patients undergoing elective hysterectomy were enrolled in this prospective, randomized, double blinded, placebo controlled trial. Subjects received either oral aprepitant 40 mg or oral placebo 30 minutes prior to induction of standardized anesthesia. The primary outcome was vomiting within the first 24 hours after surgery. Postoperative nausea, vomiting, and use of rescue antiemetics were documented over a 24 h period. Additionally, adverse events, hospitalization days, and readmissions for PONV were compared. Results: There was a trend towards reduction of postoperative nausea and vomiting in the aprepitant group. Nausea and vomiting were noted for 24% and 17% of women in the aprepitant group versus 38% and 29% of women in the Placebo group, respectively. Supplemental antiemetic medication was used by 42% of women in the aprepitant group versus 60% of women in the Placebo group. No adverse events were substantially more common in the aprepitant group than the Placebo group. Conclusions: Preemptive use of aprepitant prior to elective hysterectomy may reduce the incidence of PONV and diminish the need for rescue antiemetics postoperatively. Further studies with larger power are needed to confirm the trends observed in this study.
文摘Objective The aim of this study was to explore the clinical efficacy and toxicity of a combination aprepitant and palonosetron hydrochloride therapy in preventing chemotherapy-induced nausea and vomiting associated with a cisplatinum-based regimen in patients with lung cancer. Methods Sixty-eight patients with lung cancer were randomly assigned to receive either aprepitant plus palonosetron hydrochloride(group A, n = 38) or tropisetron(group B, n = 30). Acute(0–24 h) and delayed(2–5 d) emetic episodes, nausea, vomiting, constipation, and dizziness were compared between the two groups in the five days following cisplatinum-based chemotherapy.Results Group A had a higher complete control rate for both acute and delayed emetic episodes than Group B(36.8% vs. 13.3% and 31.6% vs. 13.3%, respectively; P < 0.05 for both). There was no significant difference in the constipation rate between the two groups. Conclusion Aprepitant combined with palonosetron hydrochloride is active and well tolerated in both acute and delayed emetic episodes in patients with lung cancer treated by a cisplatinum-based regimen.
文摘Background:Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis.The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting(CINV)in patients with solid malignant tumors,determine risk factors and externally validate different personalized risk models for CINV.Methods:This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy.The primary endpoint was complete response(CR)during the overall phase(OP)with a non-inferiority margin of 10.0%.Logistic regression modelswere used to assess the risk factors ofCRand no nausea.To validate the personalized risk models,the accuracy of the risk scoring systems was determined by measuring the specificity,sensitivity and area under the receiver operating characteristic(ROC)curve(AUC),while the predictive accuracy of the nomogram was measured using concordance index(C-index).Results:A total of 720 patients were randomly assigned.CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group(78.1%vs.77.7%,P=0.765)with a between-group difference of 0.4%(95%CI,-5.7%to 6.6%).Female sex,higher cisplatin dose(≥70 mg/m2),no history of drinking and larger body surface area(BSA)were significantly associated with nausea.The AUC for the acute and delayed CINV risk indexes was 0.68(95%CI:0.66-0.71)and 0.66(95%CI:0.61-0.70),respectively,and the C-index for nomogram CINV prediction was 0.59(95%CI,0.54-0.64).Using appropriate cutoff points,the three models could stratify patients with high-or low-risk CINV.No nausea and CR rate were significantly higher in the low-risk group than in the high-risk group(P<0.001).Conclusions:Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy.Female cancer patients without a history of alcohol consumption,with larger BSA and received high-dose cisplatin might be more vulnerable to CINV.Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.
基金fnancial support from Sichuan provincial science and technology support program (No. 2011SZ0014)
文摘The synthesis of two isomers of Aprepitant(APT)and three isomers of Fosaprepitant(FPT),crucial components for quality control in manufacturing,is described.Herein,three chiral centers in the isomers of Aprepitant are established in high yield by induced crystallization and chiral reduction.Additionally,the isomers of Aprepitant are utilized to synthesize the isomers of Fosaprepitant with the same stereochemistry.All the target compounds were confrmed by elemental analyses,IR,NMR and MS data analysis.
