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.     

Aprepitant for chemotherapy-induced nausea and vomiting

Although the development of serotonin receptor antagonists has greatly improved treatment for chemotherapy-induced nausea and vomiting, patients receiving chemotherapy continue to experience this troublesome side effect. On March 26, 2003, the U.S. Food and Drug Administration approved aprepitant (Emend, Merck & Co., Inc., Whitehouse Station, NJ) for use in combination with standard antiemetic agents for acute and delayed nausea and vomiting with initial and repeat courses of highly emetogenic therapy. Aprepitant appears to provide superior control of acute and delayed emesis compared to standard antiemetic therapy. Aprepitant was well tolerated in phase III studies, with side effects similar to standard therapy. Healthcare providers need to be aware of potential drug interactions with aprepitant. Oncology nurses continue to play a key role in helping patients adhere to their antiemetic schedules, stressing the importance of prevention of nausea and vomiting.     

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.     

Effectively managing chemotherapy-induced nausea and vomiting

This article examines the unpleasant side effect of chemotherapy-induced nausea and vomiting (CINV). What was once the main reason for withdrawing from treatment is now much more tolerable owing to the advent of modern antiemetics. However, because of the improvements in these antiemetics, the focus on CINV appears to have lapsed. Despite this, some patients continue to experience problems and under-report this side effect. This article looks at the mechanism of CINV and clarifies terminology and definitions surrounding it. Risk factors are discussed and management strategies advised, including appropriateness of modern antiemetics and non-pharmacological strategies. To conclude, a brief look at nursing implications and self-management strategies are explored.     

New treatment options for chemotherapy-induced nausea and vomiting

Significant progress has been made in the development of effective, convenient, and well-tolerated means to prevent nausea and vomiting associated with cancer chemotherapy (CINV). Nevertheless, a substantial minority of patients continues to have suboptimal antiemetic control, and additional treatment approaches are needed. One avenue of investigation being pursued involves the evaluation of a new 5-HT₃ receptor antagonist (palonosetron) that differs from available serotonin antagonists in its markedly longer half-life (40 h) and greater binding affinity for the type-three serotonin receptor. Analysis of available clinical data demonstrates that palonosetron is an active and well tolerated new 5-HT₃ antagonist. Additional studies incorporating dexamethasone and repetitive-day conventional 5-HT₃ antagonist dosing will be necessary to definitively determine the relative efficacy of palonosetron compared to available agents. Another very promising area that moves beyond serotonin focuses on Substance P as a therapeutic target. Substance P is a tachykinin found in neurons in the brainstem. It is the preferred ligand for the neurokinin-1 (NK-1) receptor. Preclinical studies with selective NK-1 antagonists have demonstrated promising antiemetic activity. Subsequent clinical trials with selective NK-1 antagonists for the prevention of CINV have validated the preclinical promise demonstrated with these agents. One agent in this new therapeutic class (aprepitant) recently received regulatory approval in the United States for use in combination with a 5-HT₃ antagonist and dexamethasone, defining a new standard of care for highly-emetogenic chemotherapy.Presented in part at the Annual Meeting of the Multinational Association of Supportive Care in Cancer, Berlin, Germany, June 19, 2003.     

Patient-controlled antiemesis for cancer chemotherapy-induced nausea and vomiting

Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (>3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of diffcult-to-treat patients.     

Progress in preventing chemotherapy-induced nausea and vomiting

Our understanding of the pathophysiology of emesis has improved over the past 2 decades, and we now have drugs that can prevent acute emesis in most patients. Prevention and treatment of the delayed and anticipatory forms of chemotherapy-induced emesis remain a challenge.     

The management of chemotherapy-induced nausea and vomiting

This paper reviews one of the major side-effects of chemotherapy, emesis. Included are patient and treatment factors that can affect the control of nausea and vomiting as well as a summary of the management of chemotherapy-induced emesis.     

Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines

As many as 40–80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting, depending on the site of irradiation. Fractionated RT may involve up to 40 fractions over a 6–8 weeks period, and prolonged symptoms of nausea and vomiting could affect quality of life. Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiotherapy. Nausea and vomiting are often underestimated by radiation oncologists. Incidence and severity of nausea and vomiting depend on RT-related factors (single and total dose, fractionation, irradiated volume, radiotherapy techniques) and patient-related factors (gender, general health of the patient, age, concurrent or recent chemotherapy, psychological state, tumor stage). Current antiemetic guidelines prescribe the emetogenicity of radiotherapy regimens and recommend the use of 5-HT₃ antagonists with or without a steroid for prophylaxis in moderately and highly emetogenic treatment (MASCC, ASCO, ASHP, NCCN). The new proposed guidelines summarise the updated data from the literature and take into consideration the existing guidelines. According to the irradiated area (the most frequently studied risk factor), the proposed guidelines are divided into four levels of emetogenic risk: high, moderate, low and minimal. They offer guidance to prescribing physicians for effective antiemetic therapies in RINV.Perugia Antiemetic Consensus Conference 2004.     

The pathophysiology of chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting is a major debilitating side effect of oncology treatment despite recent advances in pharmaceutical management. Nurses who provide care to patients experiencing nausea and vomiting are often only marginally aware of the pathophysiological processes involved in the treatment. A better understanding of the science behind current interventions to reduce nausea and vomiting may help nurses use those interventions more effectively. This article reviews current knowledge about the pathophysiology of chemotherapy-induced nausea and vomiting. By understanding the pathophysiology behind this patient experience, gastroenterology nurses can develop a better understanding of the common symptoms of nausea and vomiting in general. When a nurse understands the complexity of factors causing nausea and vomiting, he or she will be better able to provide appropriate interventions to reduce these symptoms.     

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study

Purpose  

Aprepitant was shown previously to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving an anthracycline and cyclophosphamide (AC)-based regimen. This study assessed aprepitant in patients receiving a broad range of MEC regimens with a variety of tumor types.     

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.     

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.     

Review of acupressure studies for chemotherapy-induced nausea and vomiting control

The purpose of this review was to evaluate the effects of a noninvasive intervention, acupressure, when combined with antiemetics for the control of chemotherapy-induced nausea and vomiting (CINV). Ten controlled acupressure studies were included in this review. The review evaluated one quasi-experimental and nine randomized clinical trials, which included two specific acupressure modalities, that is, acupressure band and finger acupressure. The effects of the acupressure modalities were compared study by study. Four of seven acupressure band trials supported the positive effects of acupressure, whereas three acupressure band trials yielded negative results regarding the possible effects of acupressure; however, all the studies with negative results had methodological issues. In contrast, one quasi-experimental and two randomized finger acupressure trials all supported the positive effects of acupressure on CINV control. The reported effects of the two acupressure modalities in each phase of CINV produced variable results. Acupressure bands were effective in controlling acute nausea, whereas finger acupressure controlled delayed nausea and vomiting. The overall effect of acupressure was strongly suggestive but not conclusive. Differences in the acupressure modality, the emetic potential of chemotherapeutic agents, antiemetic use, and sample characteristics of each study made study-to-study comparisons difficult. Suggestive effects of acupressure, cost-effectiveness, and the noninvasiveness of the interventions encourage researchers to further investigate the efficacy of this modality. Acupressure should be strongly recommended as an effective, nonpharmacologic adjuvant intervention for CINV control if its positive effects are reproduced in future acupressure clinical trials.