Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting

OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). DATA SOURCES: MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA EXTRACTION: Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information. DATA SYNTHESIS: The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted. CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.     

Aprepitant in antiemetic combinations to prevent chemotherapy-induced nausea and vomiting

Aprepitant is an oral neurokinin-1 receptor antagonist which acts centrally to block chemotherapy-induced emesis. Its main pathway of elimination is by the cytochrome p450 isozyme CYP3A4, which is the basis for drug interactions with dexamethasone and oral contraceptives. Aprepitant is well tolerated, and phase II trials in high-dose cisplatin-induced emesis showed that it is most effective when 125 mg orally is added to a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone for acute emesis and then an 80 mg oral dose continued with dexamethasone on days 2 and 3 to prevent delayed emesis. Two pivotal phase III trials enrolling a total of 1099 patients showed that the complete control of emesis improved by 20% in patients receiving aprepitant as compared with standard therapy, with the most impressive differences being in delayed emesis. Control was maintained over multiple cycles and occurred in both males and females and young and old adults.     

Employment of substandard antiemetic prophylaxis in recent trials of chemotherapy-induced nausea and vomiting

OBJECTIVE: To determine the prevalence of substandard antiemetic therapy among recently published trials conducted in patients with cancer who received emetogenic chemotherapy. DATA SOURCES: A MEDLINE search was conducted (2000-July 2004) using the key words 5-HT(3) antagonists, ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron, NK-1 antagonists, and aprepitant. STUDY SELECTION AND DATA EXTRACTION: All antiemetic trials in patients receiving chemotherapy that were published from January 2000 to July 2004 were evaluated. Standard prophylactic antiemetic therapy was derived from contemporary antiemetic guidelines published by oncology professional organizations and expert panels. The number of patients and studies in which patients received standard and substandard antiemetic therapy was determined for both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV). Separate determinations were made for severely and moderately emetogenic chemotherapy. The annual percentage of studies in which substandard antiemetic prophylaxis was given and the percentage of patients who received substandard prophylaxis also were determined. DATA SYNTHESIS: Fifty-six studies were reviewed, which included a total of 10 274 patients and 125 study arms. The percentage of patients who received substandard antiemetic prophylaxis was 30% (n = 3063) for acute CINV and 33% (n = 3413) for delayed CINV. The average annual percentage of studies that employed substandard prophylaxis during this time period was 54%. CONCLUSIONS: In recent antiemetic trials for CINV, the employment of substandard antiemetic therapy is common. These results raise important ethical questions regarding contemporary antiemetic trial design.     

Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review

Purpose

Newer drugs incorporated in prophylactic regimens for chemotherapy-induced nausea and vomiting (CINV) have resulted in significantly reduced rates of this feared complication of cytotoxic chemotherapy. However, both delayed chemotherapy-induced nausea and breakthrough CINV remain difficult areas of management and require novel treatment strategies. Recent randomized trial evidence has suggested that olanzapine, an atypical antipsychotic, may have a role in both the prevention and treatment of CINV. A systematic review was conducted to assess the efficacy of olanzapine in (a) preventing CINV in highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) and (b) the treatment of breakthrough CINV. The toxicity of olanzapine in this setting was also reviewed.

Methods

MEDLINE, Embase and Cochrane Database of Systematic Reviews databases were searched to identify all randomized clinical trials (RCTs) investigating olanzapine in patients receiving chemotherapy.

Results

A total of 488 patients from three trials of CINV prophylaxis and 323 patients from three trials of breakthrough CINV were included. Regimens including olanzapine were associated with significant improvements in CINV prevention with both HEC and MEC. Single agent olanzapine for breakthrough nausea was superior to standard alternative options.

Conclusion

Data from RCTs support the use of an olanzapine containing combination regimen as an option for CINV prophylaxis and single agent olanzapine for the treatment of breakthrough CINV. In the included trials, the short duration of olanzapine appears safe and well tolerated.     

Non-pharmacological management for chemotherapy-induced nausea and vomiting in patients with cancer: a scoping review

Objective: This review aimed to map and summarize published studies that tested non-pharmacological management for chemotherapyinduced nausea and vomiting(CINV). Methods: We searched for eligible studies in 5 electronic databases and screened the retrieved studies using the inclusion and exclusion criteria. Data were then collated according to the types of interventions, measurement tool, and outcomes. Results: The search yielded 2343 records, of which 11 were included. Four categories of non-ph...     

The cost of antiemetic therapy for chemotherapy-induced nausea and vomiting in patients receiving platinum-containing regimens in daily practice in Japan: a retrospective study

Purpose  

The objective of this study was to estimate the cost of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in daily practice in Japan.     

Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies

Radiotherapy-induced nausea and vomiting (RINV) can be one of the most distressing symptoms of radiotherapy treatment, which if incompletely controlled may last for several weeks with fractionated radiotherapy and prevent completion of the planned treatment course. Current treatment guidelines recommend the use of 5-HT₃ receptor antagonists with or without corticosteroids for highly and moderately emetogenic radiotherapy, though only granisetron and ondansetron are currently indicated for RINV in most countries. Granisetron is a potent and highly selective 5-HT₃ receptor antagonist, with demonstrated efficacy in RINV in both placebo-controlled and comparative studies. In this paper the clinical experience with granisetron in RINV is reviewed, and its efficacy and safety compared with other antiemetic therapies.     

Low-dose granisetron for prophylaxis of acute chemotherapy-induced nausea and vomiting: a pilot study

Objectives Chemotherapy-induced nausea and vomiting (QTNV) are very uncomfortable symptoms for patients with cancer, which can be circumvented in most of them with drug combinations containing serotonin receptor antagonists (5-HT₃ receptor antagonists) such as granisetron. In an attempt to decrease costs of QTNV prophylaxis, we studied a lower dose regimen of granisetron.Patients and methods Sixty patients with cancer scheduled to receive moderately/highly emetogenic chemotherapy were pretreated 1 h before with 0.5 mg granisetron p.o. combined with dexamethasone 20 mg i.v.Results We observed complete control for nausea, vomiting, and nausea and vomiting in 78% [95% confidence interval (CI), 67–89%], 61% (95% CI, 47.5–74.5%), and 58% (95% CI, 44.3–71.7%) of the patients, respectively. This regimen was very well tolerated; headache (35%), xerostomia (11%), and constipation (5%) were the most frequent adverse symptoms reported.Conclusions The regimen with lower dose granisetron is effective for acute QTNV prophylaxis and offers a cheaper alternative for QTNV control. We feel that these encouraging results should be confirmed in a randomized comparative trial.     

Optimizing treatment outcomes in patients at risk for chemotherapy-induced nausea and vomiting

Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial in maximizing patients' quality of life and optimizing outcomes of cancer therapy, and can be done more effectively than ever before. Appropriate antiemetic therapy combined with targeted patient education, clear communication, and management of patient expectations results in optimal emetogenic control. Oncology nurses play a critical role in the prevention and management of CINV. This column reviews the history and pathophysiology of treatments for CINV, as well as patient- and chemotherapy-specific risk factors that should be considered to optimize treatment outcomes in patients with CINV.     

Post-operative nausea and vomiting: a survey of nurses' knowledge

Many patients experience the discomfort of post-operative nausea and vomiting. This article reports on a survey to find out just how much nurses know about relieving these distressing symptoms.     

穴位按压缓解胃肠道肿瘤化疗患者恶心呕吐的效果观察

目的探讨穴位按压对缓解胃肠道肿瘤化疗患者恶心、呕吐的效果。方法对78例胃肠道恶性肿瘤患者化疗期间进行内关穴按压,用中文版恶心呕吐干呕症状评估量表评估患者化疗后出现的恶心、呕吐和干呕症状。结果统计分析显示,穴位按压对缓解化疗患者恶心、呕吐等不良反应有一定效果,且具有统计学意义(P0.01)。结论穴位按压能有效地降低患者恶心、呕吐的发生频率,缩短经历时间及减轻症状的严重程度,提高患者对化疗的耐受性,减轻痛苦。     

Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting

Goals of work  Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown. Materials and methods  We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT₃ receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding. Main results  There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group. Conclusions  Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT₃ receptor antagonists and/or aprepitant. This trial is registered in ClinicalTrials.gov ID: NCT00065221.