Use Of Aprepitant Research Articles

Reduction of soluble CD163, substance P, programmed death 1 and inflammatory markers

Objective:We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant – a neurokinin 1 receptor antagonist.Design:Phase IB randomized, placebo-controlled, double-blinded study.Methods:Eighteen patients were randomized (nine to aprepitant and nine to placebo). The patients received once-daily treatment (375 mg aprepitant or placebo by oral administration) for 2 weeks and were followed off drug for 4 weeks.Results:There were no significant changes in the plasma viremia or CD4+ T cells during the dosing period. Aprepitant treatment was associated with significant decreases of median within patient change in percentages of CD4+ T cells expressing programmed death 1 (−4.8%; P = 0.04), plasma substance P (−34.0 pg/ml; P = 0.05) and soluble CD163 (−563 ng/ml; P = 0.02), with no significant changes in the placebo arm. Mean peak aprepitant plasma concentration on day 14 was 7.6 ± 3.1 μg/ml. The use of aprepitant was associated with moderate increases in total cholesterol, low-density lipoprotein and high-density lipoprotein (median change = +31 mg/dl, P = 0.01; +26 mg/dl, P = 0.02; +3 mg/dl, P = 0.02, respectively).Conclusion:Aprepitant was safe and well tolerated. At the dose used in this proof-of-concept phase IB study, aprepitant did not show a significant antiviral activity. Aprepitant-treated patients had decreased numbers of CD4+ programmed death 1-positive cells and decreased plasma levels of substance P and soluble CD163, suggesting that blockade of the neurokinin 1 receptor pathway has a role in modulating monocyte activation in HIV infection. Prospective studies in virologically-suppressed individuals are warranted to evaluate the immunomodulatory properties of aprepitant. Exposures exceeding those attained in this trial are more likely to elicit clinical benefit.

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Aprepitant in the prevention of vomiting induced by moderately and highly emetogenic chemotherapy.

Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens.

Context:Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian population with aprepitant containing regimens.Aims:The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC) regimens.Settings and Design:Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial.Subjects and Methods:Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP) for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication) and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea) during the OP.Statistical Analysis Used:Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics.Results:Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP) for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP) were 75% and 90% for these regimens, respectively. 7 (9.2%) patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events.Conclusions:Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

Therapeutic and preventive antiemetic effect of aprepitant in Japanese patients with thoracic malignancies who truly need it.

Neurokinin-1 (NK-1) receptor antagonist is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) and has recently been introduced to oncology practice in Japan. However, whether all patients undergoing HEC truly need NK-1 receptor antagonist remains unknown, and increasing medical costs due to uniform use of NK-1 receptor antagonist are a concern. This study was conducted to examine the prevalence of patients who needed aprepitant at the time of its introduction in Japan, and therapeutic and preventive effects of aprepitant on HEC or moderately emetogenic chemotherapy (MEC). Eligible patients with thoracic malignancies who were to undergo HEC or MEC received 5-hydroxytryptamine receptor antagonists and dexamethasone to prevent CINV. Aprepitant was administered to treat CINV occurring in the first course, or to prevent CINV in the second course. Frequency of vomiting, degree of nausea, and quality of life with respect to CINV were assessed. In total, 96 patients were enrolled. Aprepitant was not administered in 57 and 88 % of patients who received HEC and MEC, respectively. In patients treated with aprepitant (n = 18), therapeutic use of aprepitant after occurrence of CINV (n = 9) decreased average scores in numerical rating scale for nausea from 7.44 to 5.44 (p = 0.10), and average frequency of vomiting per day from 2.11 to 0.11 (p = 0.03). Prophylactic use of aprepitant in the second course (n = 18) increased the proportion of patients with no significant nausea from 6 % (first course) to 50 % (second course; p = 0.007), and those with no vomiting from 33 to 89 % (p = 0.002). Aprepitant use also significantly improved quality of life with respect to CINV in the second course. More than half of patients receiving HEC and 88 % of patients receiving MEC did not use aprepitant. Aprepitant showed significant therapeutic and preventive effects on CINV in patients who truly needed it.

Association of Aprepitant and Palonosetron in Prevention of Acute and Delayed Nausea and Vomiting in High Emetogenic Chemotherapy Regimens

ABSTRACT Aim: The recently published Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) guidelines in the prevention of nausea and vomiting, recommended the use of aprepitant, dexametasone, and a serotonin antagonist (5HT3 receptor antagonist), to prevent nausea and vomiting in high emetogenic chemotherapy (HEC) schedules, although there is debate on which should be the ideal 5HT3 antagonist. Many studies have compared palonosetron with ondansetron and granisetron in the prevention of cisplatin-induced acute nausea and vomiting. The complete response was similar in the first 24 hours, but significantly superior with palonosetron on days 2–5, and on days 1–5, suggesting that palonosetron induced more protection from delayed emesis before HEC. The aim of our study is to test the efficacy of the concomitant use of palonosetron and aprepitant in preventing nausea and vomiting in HEC. Methods: We analyzed data collected from 100 consecutive patients who received HEC chemotherapy between April 2013 and May 2014 at our Institute, with various schedules for different type and stage of disease. Patients were pretreated with an antiemetogenic schedule consisting in aprepitant (oral 125 mg, on day one; oral 80 mg, on days 2 and 3), palonosetron (i.v. 0.25 mg, on day 1), and dexametasone (i.v. 12 mg, on day 1). Nausea and vomiting were classified as acute phase (within 24 hours from infusion) or delayed phase (days 2 to 5), and intensity of disorder was classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4.0. Data were collected at baseline and every cycle of therapy. Results: Day 1 complete response was 84.9%, while complete response from days 2 to 5 was 79.5%. Outcome for complete protection, total control, no vomiting, no nausea were respectively 61.2%, 52.9%, 90.3% and 53.6% for acute phase, and 54.7%, 43.2%, 89.2% and 43.9% for the delayed phase. Most reported side effect were hiccups, fatigue, constipation, headache and anorexia; no serious adverse event was reported. Conclusions: Association of aprepitant and palonosetron is an effective prophylaxis of acute and delayed emesis, with no serious toxicity reported. Phase 3 trials to compare different 5HT3 antagonists are warranted to clarify the best antiemetogenic strategy. Disclosure: All authors have declared no conflicts of interest.

Use of aprepitant in uncontrolled delayed nausea and vomiting associated with preparative regimens in stem cell transplantation: A retrospective analysis.

9613 Background: Aprepitant, a well tolerated antiemetic, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic ch...

The effect of transdermal scopolamine for the prevention of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) is one of the most common and undesirable complaints recorded in as many as 70–80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia (SAMBA) guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 h after surgery. In an effort to find a safer and reliable therapy for PONV, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl) benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a non-selective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2)-scopolamine (tropic acid ester with scopine; MW = 303.4). Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 h. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in PONV. Thus, scopolamine is a promising candidate for the management of PONV in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long-lasting clinical effects.

Economic analysis of aprepitant‐containing regimen to prevent chemotherapy‐induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Hong Kong

We aim to evaluate the cost effectiveness of aprepitant-containing regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) in Hong Kong. Both cost-effectiveness and cost-utility analyses were conducted utilizing a decision-analytic model to measure the economic costs and clinical outcomes associated with the aprepitant-containing regimen versus a standard regimen in the prevention of CINV. Analyses were conducted on the basis of four published double-blind randomized clinical trials involving different usages of serotonin receptor antagonists. The use of aprepitant-containing regimens is associated with an improvement in quality-adjusted life years (QALYs) compared with non-aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is administered on day 1 only. The incremental cost per QALY is HKD 440,950 when ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide chemotherapy, the aprepitant-containing regimen is associated with incremental cost of HKD 195,442 per QALY gained. Similar results were obtained when other 5HT3 receptor antagonists are used. The use of aprepitant was associated with higher cost of drug but lower costs of emesis-related management. With the cost-effectiveness threshold set at the World Health Organization endorsed criteria of three times gross domestic product (GDP) per capita (three times GDP per capita in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the aprepitant-containing regimen was cost-effective. In patients undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in Hong Kong.

Risk Factors for Early-Onset Peripheral Neuropathy Caused by Vincristine in Patients With a First Administration of R-CHOP or R-CHOP-Like Chemotherapy.

BackgroundPeripheral neuropathy is a well-known side effect of vincristine (VCR), a microtubule inhibitor used for R-CHOP or R-CHOP-like (namely R-CVP and R-THP-COP) regimens. Previous studies have shown that both the total dose of VCR and the number of treatment cycles are related to the incidence of VCR-induced peripheral neuropathy (VIPN). However, VIPN will also occur during the first treatment cycle regardless of the total dose of VCR or number of treatment cycles (early-onset VIPN). There is little information about early-onset VIPN, and it is difficult to predict. The present study’s goal was to identify risk factors for early-onset VIPN.MethodsWe analyzed the case records of patients who had their first administration of an R-CHOP or R-CHOP-like regimen between April 2008 and August 2013 at Tokushima University Hospital in Tokushima, Japan. To identify the risk factors for early-onset VIPN, we performed univariate and multivariate logistic regression analyses.ResultsForty-one patients underwent an R-CHOP or R-CHOP-like regimen for the first time at Tokushima University Hospital between April 2008 and August 2013, and 14 patients had grade 1 or higher early-onset VIPN. A univariate analysis revealed that age, the dose of VCR and the concomitant use of aprepitant appeared to be the risk factors of early-onset VIPN. In our calculation using receiver-operator characteristics curves, the cut-off value for patient age was 65 years and that of the dose of VCR was 1.9 mg. A multivariate analysis revealed that VCR dose ≥ 1.9 mg and the concomitant use of the antiemetic aprepitant were independent risk factors for early-onset VIPN.ConclusionsOur present study showed that the patients who had VCR dose ≥ 1.9 mg and the concomitant use of aprepitant had the risk for early-onset VIPN. This suggests that it is important to use aprepitant in light of the risk of early-onset VIPN and the benefit of aprepitant’s antiemetic effect in R-CHOP and R-CHOP-like regimens.

A Randomized Controlled Study Evaluating The Efficacy Of Aprepitant For Highly Emetogenic Chemotherapies In Hematological Malignancies

▪ BackgroundChemotherapy induced nausea and vomiting (CINV) is a serious complication of treatments of hematological malignancies. Although 5HT3 blocker achieved modest control of acute phase CINV (<24 h of chemotherapy), prevention of delayed phase CINV (>24 h after chemotherapy) remained a challenge. Aprepitant, the oral neurokinin-1 receptor antagonist, has been revealed to have anti-emetic efficacy against both acute and delayed phase CINV in highly emetogenic therapies for solid tumors. However, its effect in the treatment of hematological malignancies has not been established. Thus we conducted a randomized controlled study to evaluate the efficacy of aprepitant in patients receiving chemotherapeutic agents for hematological malignancies. Patients and methodsWe examined the additional effect of aprepitant to conventional 5HT3 blocker-based prophylaxis for CINV in induction/consolidation of acute leukemia (n=18), platinum containing regimens for malignant lymphoma (n=18), and preparative regimens of autologous stem cell transplantation (n=5). The primary endpoint of this study was the overall complete response (CR), which was defined as no emetic episodes or no administration of rescue medications during the 10 days after the start of chemotherapies (overall period). Response rates in the acute and delayed phase were also analyzed. Secondary endpoints were the rate of (1) emesis, (2) rescue medications, and (3) significant nausea scored in visual analog scale (VAS) by patients themselves during the total study period or in acute or delayed phase. Oral food intake was also evaluated by patients. ResultsA total of 49 patients were enrolled and 41 of whom (n=22 in the aprepitant arm and n=19 in the control arm) were eligible for analysis. There was no withdrawal due to the adverse effects of aprepitant. CR rates of the aprepitant and control arms were 82% and 68% in the acute phase (p=0.47) and 82% and 58% in the delayed phase (p=0.17), respectively. Overall CR was significantly higher in the aprepitant arm (82% versus 47%, p=0.026). Emetic episodes during the entire observation period were seen at a higher rate in the control arm (9% in the aprepitant arm versus 42% in the control arm, p=0.026) and the control arm tended to have more emetic episodes than the aprepitant arm both in the acute (5% in the aprepitant arm versus 26% in the control arm, p=0.08) and delayed phases (9% in the aprepitant arm versus 37% in the control arm, p=0.057). Whilst the administration rate of salvage anti-emetic therapies was almost the same between the two arms in the early phase (14% in the aprepitant arm versus 16% in the control arm, p=1), this rate tended to be lower in the aprepitant arm in the delayed phase (18% in the aprepitant arm versus 26% in the control arm, p=0.71). In the evaluation of nausea sensation by VAS, the control arm had a trend toward higher score in the late phase. The self-assessed daily oral food intake revealed that about 50% of the patients in the aprepitant arm maintained usual amounts of food intake throughout the observation period whereas this rate dropped significantly in the control arm at day 6 (p=0.049). In the sub-group analyses to find the traits that would potentially favor aprepitant use, patients with therapies for acute leukemia had little benefit from aprepitant use (Odds ratio=0.74, p=1.0). This is probably due to moderate emetogenicity of this group, as substantiated by high CR rate in the control arm (80%). ConclusionsAprepitant confers additional anti-emetic effect to conventional 5HT3 blocker-based regimens in moderately/highly emetic chemotherapies for hematological malignancies. Disclosures:Nannya:Ono Pharmaceutical Co., Ltd: Research Funding. Kurokawa:Ono Pharmaceutical Co., Ltd: Research Funding.

Aprepitant use in children with cyclical vomiting syndrome

Objectives and study: Cyclic vomiting syndrome (CVS) is a chronic disorder characterized by recurrent, stereotypical episodes of nausea and vomiting interspersed with symptom-free periods. In a subgroup of children, both acute and prophylactic standard treatments remain unsatisfactory. Aprepitant, a neurokinin-1 receptor antagonist, is efficacious in preventing chemotherapy-induced nausea and vomiting in adults and older children; its role in other disorders remains to be defined. In this study we assessed the efficacy of aprepitant as a prophylactic/acute treatment in CVS children refractory to standard therapies.

The use of aprepitant in the first cycle of moderately emetogenic chemotherapy in patients with colorectal cancer: its preventive effect on chemotherapy-induced nausea and vomiting

Purpose: There have been fever studies about the effectiveness of aprepitant in the first cycle of moderately emetogenic chemotherapy. The aim of this study was to determine whether aprepitant shows the effectiveness for prevention of chemotherapy-induced nausea and vomiting in the first cycle of moderately emetogenic chemotherapy in colon cancer patients. Methods: A total of 131 patients who received their first chemotherapy (FOLFOX4, mFOLFOX6, or FOLFIRI regimen) for colon cancer were retrospectively analyzed. Eighty-one patients received aprepitant, 5HT3-receptor antagonist and dexamethasone (aprepitant group) and 50 patients received 5HT3-receptor antagonist and dexamethasone without aprepitant (control group) in the first cycle of moderately emetogenic chemotherapy. We compared the outcomes of the response and the incidence of adverse events. Results: Both groups were similar in baseline characteristics. The complete response rate was significantly higher in the aprepitant group during 24 hours postchemotherapy (98.8% vs. 90.0%, P=0.02), between 24 to 120 hours postchemotherapy (96.3% vs. 86.0%, P=0.031), and during the 120 hours postchemotherapy (96.3% vs. 82.0%, P=0.006). The overall incidence of adverse events was similar between the aprepitant and the control group as 30% vs. 26%, respectively. Conclusion: The use of aprepitant combination with 5HT3-receptor antagonist and dexamethasone showed a significant difference in response rate of chemotherapy-induced nausea and vomiting in the first cycle, suggesting that aprepitant would be necessary as a standard antiemetic agent from the first cycle of moderately emetogenic chemotherapy in colon cancer patients.

Efficacy and Safety of Aprepitant in Allogeneic Hematopoietic Stem Cell Transplantation

Study ObjectiveTo evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT).DesignRetrospective medical record review.SettingHematology ward of a university hospital in Japan.PatientsOf 88 patients treated with high-dose chemotherapy followed by allo-HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010).InterventionsPatients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60–90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3–6 days).Measurements and Main ResultsThe primary objective was to evaluate the percentage of patients who achieved complete response (CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.13–7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups.ConclusionsThe addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo-HSCT.

CPC-087 Monitoring Antiemetic Regimens with Aprepitant in Cancer Patients

BackgroundAfter including aprepitant in the hospital’s pharmacotherapy guide 5 years ago, we decided to cheque if it is being used as defined by the Drug and Therapeutics Committee, which approved...

Use of Oral Aprepitant for the Management of Nausea with Inpatient Intravenous Dihydroergotamine (DHE) Use (S40.006)

Use of Oral Aprepitant for the Management of Nausea with Inpatient Intravenous Dihydroergotamine (DHE) Use (S40.006)

Effectiveness and Safety of Antiemetic Aprepitant in Japanese Patients Receiving High-Dose Chemotherapy Prior to Autologous Hematopoietic Stem Cell Transplantation

For patients receiving high-dose chemotherapy, a 5-hydroxytryptamine 3 receptor antagonist combined with dexamethasone is a standard antiemetic therapy. Despite this prophylactic anti-emetic treatment, many patients still suffer from uncontrollable emesis. In this study, we retrospectively evaluated the antiemetic effectiveness and safety of aprepitant (a neurokinin-1 receptor antagonist) in addition to 5-HT3 antagonist in Japanese patients with hematologic malignancy receiving high-dose chemotherapy prior to autologous peripheral blood stem cell transplantation (auto-PBSCT). Twenty-six patients received aprepitant and granisetron (the aprepitant group), whereas, 22 patients received granisetron alone (the control group). All patients received 3 mg of granisetron intravenously 30 min before chemotherapy administration. Patients in the aprepitant group additionally received 125 mg of aprepitant 60-90 min before administration of the first moderately to highly emetogenic chemotherapy. On the next day or thereafter, 80 mg of aprepitant was administered in the morning until the last administration of moderately to highly emetogenic anticancer drugs. The percentage of patients who achieved complete response (CR), defined as no emesis with only grade 1-2 nausea, in the aprepitant group was significantly higher than that in the control group (42% vs. 5%, p=0.003). Logistic regression analysis showed that non-prophylactic use of aprepitant was significantly associated with non-CR. The frequencies of adverse drug events (ADEs) were not significantly different between two groups. In conclusion, the results of this study suggest that the addition of aprepitant to granisetron can improve the antiemetic effect without increasing ADEs in patients receiving high-dose chemotherapy prior to auto-PBSCT.

Persistence of quality improvement in a Veterans Affairs (VA) academic practice assessed by Quality Oncology Practice Initiative (QOPI).

209 Background: The success of quality improvement (QI) efforts is usually assessed initially within a year of implementation but performance may later decline. We sought to determine the longer-term effectiveness of practice improvement interventions and the characteristics of interventions associated with persistent improvement. Methods: The Durham VA Hem-Onc fellowship program affiliated with Duke University participated in QOPI twice yearly in 2007 to 2010 and Spring (Sp) 2012. Four interventions were implemented focused on treatment planning (TP; Sp07), treatment summary (TS; Fa07), consent (C; Sp07), and aprepitant use (A; Sp09). Effectiveness was determined by reassessment of 4, 3, 1, and 1 measures, respectively. The TP, TS, and C interventions were policy-dictated use of templated documentation or written consent, and, for TP and C, required conformance prior to chemotherapy administration; TS is not linked to a process. The A intervention modified order set templates to include A for highly emetogenic regimens. For each measure, we compared conformance pre-intervention with post-intervention conformance and, for quality indicators not targeted for improvement, the baseline with each subsequent assessment using chi-square. Results: Considering only measures in the core or symptom management modules with unchanged or similar definitions throughout the study period, 13 of 28 measures had conformance &gt; 85% in the baseline 2007 data. TP conformance increased from 64% to 88, 94, 92, and 96% in subsequent years (p &lt; 0.01). TS was 45% at baseline, 43% (p = NS) in the first post-intervention year, decreased to 24% for two years (p &lt; 0.01) and then increased to 38% (p = NS). C increased from 64% to 97, 91, 94, and 100% (p &lt; 0.01). Conformance with A increased from 9% to 78 and 86% (p &lt; 0.01). Among measures not targeted by intervention, smoking assessment and counseling increased in later years. Conclusions: In this single practice experience, QI improvement interventions integrated into physician processes resulted in substantial and persistent improvement while no improvement was observed as a result of policy-required use of standard documentation alone.

P1-097 - Correlation between Low-Dose Cyclophosphamide-Induced Hyponatremia and the Use of Aprepitant

ABSTRACT Background For the prevention of nausea/vomiting during anthracyline/cyclophosphamide (CPA) therapy for breast cancer, the use of aprepitant (AP) combined with serotonin antagonist and dexamethasone is recommended. It has been reported that AP does not influence AUC's of 4-hydro-cyclophosphamide, an active metabolite of CPA and DCE, a CPA-metabolite causing nephrotoxicity. Although, in the previous clinical reports for anthracyline/CPA, the toxicities were not significant in patients who were given AP, compared with those without AP, we have experienced several cases of severe hyponatremia probably caused by AP. Occurrence of hyponatremia during chemotherapy might be an issue to be cautious. Methods We investigated serum levels of Na in 67 breast cancer patients who received CPA-combined therapy with the use of AP or not. They all received 600 mg/m2 of CPA combined with either of doxorubicine, epirubicin, or docetaxel. Their prior electrolytes were to be within the normal range. In the first cycle, we evaluated serum Na levels before the CPA start and those of 24 h after. We defined a serum Na level lower than 135 mEq/l as ‘hyponatremia’. Results The background between the two groups, with AP and without AP, was comparable, in whom the prior Na levels were 140.0 ± 1.97 and 140.1 ± 1.88 mEq/l, in the AP group and in the non-AP group, respectively. The chemotherapies including CPA, the clinical stages, the uses of serotonin-receptor antagonist and dexamethasone were comparable between the two groups. Hyponatremia occurred in 11 of 42 (26.2%) patients in the AP group, whereas 2 of 25 patients (8.0%) in the non-AP group. Since the rate in the non-AP group was comparable with the previous reports, hyponetremia seemed to occur frequently in the AP group. The average Na level at 24 h after chemotherapy was 136.429 ± 3.94 mEq/L in the AP group and 138.68 ± 3.05 mEq/l in the non-AP group, respectively. Among 11 patients who developed hyponateremia, they were resolved within 48 h without any treatments in 10 patients and only one needed the Na replacement. The patient did not develop hyponatremia without using AP in the third cycle. Conclusions According to our cohort study, AP might frequently cause hyponatremia in the CPA-combined chemotherapy.

O3-010 - Evaluation of Aprepitant as Prophylactic Antiemetics of Cisplatin Split Regimen Combination with Radiation

ABSTRACT Background The emetic risk classification of cisplatin is different according to guidelines and its doses. In Japan, cisplatin split regimen, which is classified as highly emetogenic risk, has been recommended the use of aprepitant, together with 5-HT3 receptor antagonist and dexamethasone. However, cisplatin split regimen has not been investigated enough for validation of the use as an aprepitant. Purpose To evaluate the efficacy of 3 days aprepitant administration in cisplatin split regimen (20 mg/m2/day; days 1–4, 22–25, 43–46) in combination with radiation. Subjects and methods In this study, we used patients' records retrospectively. We compared the worst grade of nausea in 23 patients who had used aprepitant (group A: January 2010 to June 2010) and 34 patients who did not use aprepitant (group B: July 2011 to December 2012). Results In group A, median age: 60 years [range 35–73], male/female: 18/5, and ECOG PS 0/1: 20/3. In group B, median age: 62 years [range 31–71], male/female: 30/4, and ECOG PS 0/1: 31/3. Worst nausea grade was 0/1/2: 21/2/0 in group A and 0/1/2: 19/9/6 in group B. The percentage of nausea was significantly lower in group A compared with group B (8% versus 44%, P Conclusion Aprepitant could be effective in cisplatin split regimen as prophylactic antiemetics.