Chemotherapy-induced Nausea And Vomiting Events Research Articles

NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.

The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox.During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox.There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

Intergenerational comparison of 5-HT3RA in the prevention of chemotherapy-induced nausea and vomiting in gastric cancer patients receiving cisplatin-based chemotherapy: an observational study using a Japanese administrative claims database.

In chemotherapy-induced nausea and vomiting (CINV), the superiority of the second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) over the first-generation 5-HT3RA is shown in the delayed emesis in cycle 1. We evaluate the antiemetic efficacy in real-world clinical practice that has not been sufficiently investigated in clinical trials. We included patients who were diagnosed with gastric cancer between April 2012 and June 2017 from the medical claims databases and were treated with cisplatin (≥ 50mg/m2) and standard antiemetic therapy (5-HT3RA + neurokinin-1 receptor antagonist [NK1RA] + dexamethasone). We compared the second-generation 5-HT3RA (2nd group) and the first-generation 5-HT3RA (1st group) groups to evaluate the additional antiemetic drug as the CINV event. In total, 3798 patients were extracted; 1440 and 2358 patients were included in the 1st and 2nd groups, respectively. The clinical and demographic characteristics did not differ between the groups. In the overall (days 1-6) in cycle 1, 51.7% and 44.3% of patients in the 1st and 2nd groups, respectively, had a CINV event. In the acute phase (days 1-2), 38.7% and 30.2% and in the delayed phase (days 3-6), 35.8% and 32.1% of patients in the 1st and 2nd groups, respectively, had a CINV event. Furthermore, the CINV event trend was the same as in cycles 1 to 5. The proportion of CINV events in the 2nd group was smaller than that in the 1st group at any cycle. These findings may suggest consistent antiemetic efficacy of second-generation 5-HT3RA throughout the cycle.

Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study

BackgroundNEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle.MethodsIn this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined.ResultsOf the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65–0.50 for no CINV events on cycles 3 and 4).ConclusionThe high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle.Trial registrationThis trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

Risk Analysis for Chemotherapy-induced Nausea and Vomiting (CINV) in Patients Receiving FEC100 Treatment.

Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.

Budget impact of netupitant/palonosetron for the prevention of chemotherapy-induced nausea and vomiting

Background: Chemotherapy-induced nausea and vomiting (CINV) are among the most common and debilitating side-effects patients experience during chemotherapy, and are associated with considerable acute care use and healthcare cost. It is estimated that 70–80% of CINV could be prevented through appropriate use of CINV prophylaxis; however, suboptimal CINV compliance and control remains an issue in clinical practice. Netupitant/palonosetron (NEPA) is a fixed combination of serotonin-3 (5-HT3) and neurokinin-1 (NK1) receptor antagonists (RAs), respectively, indicated for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Phase 3 clinical trials showed a significantly higher complete response rate in both acute and delayed CINV in chemotherapy-naïve patients receiving NEPA compared to patients receiving palonosetron. Objective: The objective of this study was to estimate the budgetary impact of adding NEPA to a US payer or practice formulary for CINV prophylaxis. Methods: A model was developed to estimate the impact of adding NEPA to the formulary of a hypothetical US payer with 1.15 million members, including 150,000 (13%) Medicare beneficiaries. The model compared the annual total costs of CINV-related events and CINV prophylaxis in two scenarios: base year (no NEPA) and comparator year (10% and 5% NEPA usage in HEC and MEC patients, respectively). A univariate sensitivity analysis was conducted to explore the effect of variability in model parameters on the budget impact. Results: A total of 2,021 patients were eligible to receive CINV prophylaxis. With NEPA, CINV prophylaxis costs increased by 0.7% ($3,493,630 vs $3,518,760) while medical costs associated with CINV events decreased by 3.9% ($15,118,639 vs $14,532,442), resulting in a net cost saving of $561,067 (3.0%) for the health plan ($18,612,269 vs $18,051,202), or $0.04 per member per month. This was equivalent to saving $5,011 per patient moved to NEPA. Among all 5-HT3 RA + NK1 RA regimens, NEPA was associated with the lowest CINV-related costs, leading to the lowest total cost of care. Conclusions: Adding NEPA to a payer or practice formulary results in a net decrease in the total budget due to a substantial reduction in CINV event-related resource utilization and medical costs, and an increase in pharmacy costs <1%, saving over $5,000 per patient.

Characterizing and assessing antiemetic underuse in patients initiating highly emetogenic chemotherapy.

Patients initiating highly emetic chemotherapy (HEC) are at a 90% risk of chemotherapy-induced nausea and vomiting (CINV). Despite guideline-concordant antiemetic prescribing preventing CINV in up to 80% of patients, studies suggest that guideline-concordant antiemetic regimen use by patients initiating HEC is sub-optimal. However, these studies have been limited to single-site or single-cancer type with limited generalizability. The objective of this study was to describe antiemetic fill regimens and to assess predictors of underuse in the USA. Our study population was adult patients under the age of 65 with cancer initiating intravenous HEC between 2013 and 2015 with employer-sponsored insurance in the IBM Watson/Truven MarketScan Commercial Claims database (N = 31,923). Descriptive statistics were used to explain antiemetic prescribing patterns, including antiemetic underuse. Modified Poisson regression was used to identify factors associated with antiemetic underuse. Among individuals initiating HEC, 49% underused guideline-concordant antiemetics. Most classified as under-using lacked an NK1 fill. While dexamethasone and 5HT3A uptake was over 80%, olanzapine use was minimal. Having lower generosity for prescription and medical benefits (paying more versus less than 20% out-of-pocket) increased the underuse risk by 3% and 4% (RR,1.03; 95% CI,1.01-1.05; P = 0.01 and RR,1.04; CI, 1.00-1.09; P = 0.03), respectively. Additionally, compared to receiving chemotherapy in the physician office setting, patients were at a 28% (RR, 1.28; 95% CI, 1.25-1.30; P < 0.0001) higher underuse risk in the outpatient hospital setting. Antiemetic underuse is high in patients initiating HEC, potentially leading to avoidable CINV events. We found that insurance generosity has a minimal effect on antiemetic guideline concordance in this population, suggesting discordance may be the result of site of care as well as gaps in provider knowledge or accountability.

Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

Evaluation of daily breakthrough chemotherapy-induced nausea and vomiting (CINV) rates in a phase III study of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen.

120 Background: Antiemetic trials typically evaluate CINV control during acute (Day 1), delayed (Days 2-5), and overall (Days 1-5) phases post-chemotherapy; the daily course of events is often unstudied in the delayed phase. In a head-to-head study evaluating NK1RA-containing regimens, a single dose of NEPA, an oral fixed combination of the NK1RA netupitant and 5-HT3RA palonosetron, was non-inferior to a 3-day regimen of APR and GRAN for overall complete response (no emesis/no rescue use) rates (74% NEPA vs 72% APR/GRAN) in 828 patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). This secondary analysis explores daily rates of breakthrough CINV in this study. Methods: This was a double-blind study in chemotherapy-naïve patients with solid tumors. Daily rates of breakthrough CINV, defined as the % of patients with emesis and/or rescue use were calculated with differences between treatment groups evaluated by the Cochran-Mantel-Haenszel method stratified by sex. Results: While daily rates of patients with breakthrough CINV remained stable between 13%-15.1% for APR/GRAN, they declined from 15.5% to 8% over the 5 days for NEPA, with the difference between groups reaching statistical significance on Day 5 (Table). Percent of total patient days with CINV events were 11.7% [NEPA] and 14.0% [APR/GRAN]. The % of patients with ≥ 3 days of breakthrough CINV were 8.5% and 12.3%, respectively. Conclusions: In this study evaluating guideline-recommended antiemetic regimens for HEC, CINV was prevented in most patients during the overall phase yet breakthrough CINV on individual days differed between treatment groups. APR/GRAN showed a relatively constant rate over time, while NEPA rates decreased and patients had fewer total days with breakthrough. This suggests the need for close monitoring of CINV events during the delayed phase. [Table: see text]

Hospitalization costs for nausea and vomiting: A savings opportunity.

155 Background: Nausea and vomiting (NV) are tracked by CMS as 2 of 10 top drivers of potentially avoidable hospital admissions for patients with cancer. These admissions pose a savings opportunity, yet limited literature exists on the costs of chemotherapy-induced NV (CINV). Burke’s 2010 assessment of 19,139 patients from 2004-2007 found CINV hospitalizations cost $7,448 and comprised the majority of overall CINV events and costs vs ambulatory events. Rashid (2016) evaluated 1,682 patients with metastatic breast cancer from 2007-2011 and found CINV admissions cost $10,074 in 2013 US dollars. Using data from the US Agency for Healthcare Research and Quality ’s Healthcare Cost and Utilization Project website (HCUPnet), and after applying adjustment factors from recent literature, we evaluated the cost of NV hospitalizations. Methods: Data on US hospital discharges for NV (based on primary discharge diagnosis) were obtained for 2014 from HCUPnet. Charges were adjusted using Smith’s (2015) model showing commercial insurers paid 48.7% of their hospital charges. They were further modified to include professional fees equaling 26.4% of facilities paid amounts, as reported by Peterson (2015). The CPI-Medical rate was used to adjust costs to 2016 dollars. A US payer perspective was used. The proportion of total NV discharges due to CINV is not known; it is also unknown whether charges for CINV differ from those for NV overall. Results: HCUPnet reported 37,730 hospital discharges for NV, with mean charges of $23,603 per event. The mean payment to hospitals, after adjustment to reflect amounts insurers actually paid, was estimated at $11,232 per event. Adding physicians’ professional fees incurred in the hospital setting yet normally charged separately yielded a total hospitalization cost of $14,197 ($15,120 in 2016 US dollars). Conclusions: Hospitalization for NV is common and costly; adjusted paid amounts averaged &gt; $15,000 per discharge, a level consistent with the CINV literature. This economic impact, in addition to the consequences for patients’ quality of life, suggests the need for continued advances in preventing CINV and optimizing compliance with national antiemetic guidelines, particularly for chemotherapy with high emetogenic potential.

Evaluating the antiemetic administration consistency to prevent chemotherapy-induced nausea and vomiting with the standard guidelines: a prospective observational study.

Nausea and vomiting (NV) are the most prevalent adverse effects of chemotherapy (CT). This study was conducted to evaluate adherence of the health care team to standard guidelines for antiemetics usage to prevent acute chemotherapy-induced nausea and vomiting (CINV) in a large CT center. A prospective study was performed during an 11-month period on patients receiving CT. A form was designed to collect patients’ demographic information and their chemotherapeutic and antiemetic regimen data. The Likert scale was used to measure the effectiveness of the antiemetics in patients. In this study, the effect of patient-related risk factors on the incidence rate of CINV was examined. Based on the results, CINV events were reported by 74.4% of patients. The antiemetic regimen of 71.2% of the patients complied with the guidelines. The complete response, complete protection, and complete control end points did not differ significantly between patients undergoing guidelines-consistent prophylaxis or guidelines-inconsistent prophylaxis. The females clearly showed a higher incidence rate of CINV (P=0.001) during the first course of CT (P=0.006). A history of motion sickness did not affect the incidence of NV. The maximum compliance error occurred for the use of aprepitant, as 16.16% of the patients who were receiving aprepitant did not comply with its instructions. The results of this study highlight how CINV was controlled in this center, which was significantly lower than that of the global standard. Perhaps, factors such as noncompliance to antiemetic regimens with standard guidelines and the failure to adhere to the administration instructions of the antiemetics were involved in the incomplete control of CINV.

Evaluation of chemotherapy-induced nausea and vomiting (CINV) events and associated resource utilization for CINV in patients(pts) treated with highly emetogenic chemotherapy (HEC) and carboplatin (Carbo) and palonosetron (palo)-based anti-emetic regimens.

e21649Background: This study assesses CINV events and resource utilization for CINV in pts treated with HEC and carbo with palo-based CINV regimens in a payer database. Methods: The cohort was rand...

Understanding the impact of settings of care and the development of chemotherapy-induced nausea and vomiting within a population of commercially insured patients.

298 Background: Research evaluating the impact of different clinical practice patterns according to settings of care and oncology patient outcomes is limited. This study describes chemotherapy-induced nausea and vomiting (CINV) rates in chemotherapy (CT) naïve cancer patients starting CT in a hospital outpatient (HOP) or community outpatient (COP) setting. Methods: Using the Optum Normative Health Information Database, patients with a new claim of CT and ≥1 outpatient cancer diagnosis claim between 1/1/06 – 6/30/12 were identified. Patients with previous inpatient cancer diagnoses, multi-day CT regimens or Medicare/Medicaid patients were excluded. CINV was defined using relevant claims-based ICD-9-CM diagnosis and procedure codes or a prescription claim for antiemetics within days 2-7 of 1st 8 CT cycles or 1st 6 months following the index CT claim. CINV events were evaluated descriptively and using regression models Results: Patients receiving CT in HOP vs. COP were similar in age. Patients receiving CT in COP vs. HOP setting were more likely to be female (78.7% vs. 62.8%), breast cancer patients (66.8% vs. 46.7%), live in the South region (49.7% vs. 44.1%) and have higher baseline healthcare costs (mean $24,950 vs. $24,629) (all p&lt;0.05). Patients in the HOP vs. COP settings had higher Charlson Comorbidity Index scores (mean 3.9 vs. 3.3, p &lt; 0.05). More CINV events were reported for patients in COP vs. those in HOP settings (p &lt; 0.05) (Table). After adjusting for clinical and demographic factors, number of CINV events remained higher for COP vs. HOP settings. However, we were unable to control for antiemetic prophylaxis use or CT emetogenic potential, due to coding irregularities. Conclusions: Results suggest cancer patients starting CT in COP vs. HOP settings may have more CINV events. However, further analyses are needed to explore the impact of antiemetic prophylaxis use or CT emetogenic potential on CINV events between settings of care. [Table: see text]

Investigating rates of CINV across settings of care in Medicare: A retrospective claims-based analysis.

297 Background: Clinical practice may differ according to settings of care and may impact both the quality of care delivered and, ultimately, patient outcomes. This study describes the differences in chemotherapy-induced nausea and vomiting (CINV) rates between chemotherapy (CT) naïve Medicare cancer patients starting CT in a hospital outpatient (HOP) or community outpatient (COP) setting. Methods: Using the 5% Medicare Fee-for-Service standard analytic files, patients with a new claim of CT and ≥1 outpatient cancer diagnosis claim between 1/1/10 – 6/30/11 were identified. Patients with a previous inpatient cancer diagnosis, multi-day CT cycles or who switched CT relevant to emetogenic potential were excluded. CINV was defined using relevant claims-based ICD-9-CM diagnosis and procedure codes within days 2-7 of the first 8 single-day CT cycles or the first 6 months following the index CT claim. CINV events were evaluated descriptively and using regression models. Results: Medicare patients receiving CT in HOP (n=1,007) vs. COP (n=1,080) were similar in demographics such as age, race, and baseline healthcare costs. However, Medicare patients receiving CT in COP compared to those in HOP settings were more likely to be female (57.0% vs. 44.7%), breast cancer patients (27.6% vs. 16.0%), live in the South region (37.7% vs. 32.3%), have higher Charlson Comorbidity Index scores (mean 5.2 vs. 4.8) and receive moderately to highly emetogenic CT (44.1% vs. 36.0%) (all p&lt;0.05). Overall, 13.9% had any CINV in the evaluation period. More CINV events per patient were reported among those in COP compared to those in HOP settings (0.43 vs 0.27, p &lt;0.05). However, differences between settings of care were not shown to be significantly different in adjusted regression analyses (p=0.177). Conclusions: We found the population characteristics between Medicare patients treated with CT in HOP and COP to vary on a number of factors. However, after controlling for these differences, our results suggest the number of CINV events was similar across settings of care. Future research should further clarify how differences in quality of care for antiemesis between COP and HOP settings may impact the incidence of CINV events in this population.

Palonostron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) during gemcitabine/cisplatin (GC) in urothelial cancer (UC) patients: A multi-institutional retrospective study in Japan.

362 Background: GC combination chemotherapy of is a standard regimen for advanced UC. Although this is a highly emetogenic chemotherapy, there has been no study concerning antiemetic prophylaxis for CINV during GC. The aims of this study were to evaluate CINV during GC and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-HT3 receptor antagonists and dexamethasone. Methods: We conducted a retrospective multi-institutional review of the medical records of 122 patients who received GC for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled CINV events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake. Nausea, vomiting, and anorexia were classified using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Results: A total of 75 and 47 patients were treated with first-generation 5-HT3 receptor antagonists (ondansetron or granisetron) plus dexamethasone (group 1) and palonosetron with dexamethasone plus aprepitant (group 2), respectively. There was no significant difference in age, sex, or the dose of cisplatin between the 2 groups. Patients in group 2 had significantly higher CR (defined as no emetic episodes and no rescue medication use) rates than those in group 1 during the overall phase in the first cycle (85.7% versus 65.3%, p=0.012) and all cycles (78.7% versus 50.7%, p=0.0019) of GC. Patients in group 2 were more likely to achieve more favorable CINV control, e.g., a lower grade of nausea, vomiting, or anorexia, lower incidence of rescue therapy required, and shorter time to become CINV-free, than patients in group 1. Conclusions: This study shows that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in UC patients treated with GC than first-generation 5-HT3 receptor antagonists plus dexamethasone.

Impact of cancer‐related fatigue on chemotherapy‐induced nausea and vomiting in Asian cancer patients

Cancer-related fatigue (CRF) has been suggested to be associated with the occurrence of chemotherapy-induced nausea and vomiting (CINV). This study aims to evaluate the potential of CRF in predicting the occurrence of CINV. This is a prospective, observational study. Recruited patients received moderately to highly emetogenic single-day chemotherapy regimens. On the day of chemotherapy, patients were instructed to provide a score (Likert scale of 0-10) to describe how CRF interfered with his or her ability to engage in daily activities and a score for how severe it was. Patients were then given a standardized 5-day diary to document their CINV events. A total of 473 eligible patients (median age: 55 years, interquartile range (IQR): 48-61 years) were recruited, with most of the patients diagnosed with gastrointestinal (45%) and breast (37%) cancers. The median score of fatigue interference was 3 (IQR: 0-5). After confounders were adjusted for, patients with low fatigue interference scores (≤3) were more likely to achieve complete protection (no nausea, no vomiting, and no breakthrough antiemetics) of CINV (adjusted odds ratio = 1.57, 95%CI [1.05, 2.35], p = 0.027). This is the largest study to date to evaluate the association between CRF and CINV. Patients experiencing CRF possessed a higher risk of poor control for CINV.

P1-126 - Palonostron with Aprepitant–Dexamethasone to Prevent Chemotherapy-Induced Nausea and Vomiting During Gemcitabine/Cisplatin in Urothelial Cancer Patients

ABSTRACT Background The combination of gemcitabine and cisplatin (GC) is a standard regimen for advanced urothelial cancer (UC). Although this is a highly emetogenic chemotherapy, there has been no study concerning antiemetic prophylaxis for chemotherapy-induced nausea and vomiting (CINV) during GC. The aims of this study were to evaluate CINV during GC and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using ondansetron and dexamethasone. Methods We conducted a retrospective review of the medical records of 52 patients who received GC for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled CINV events were identified through records of nausea and vomiting, additional infusion, rescue medications and/or records of food intake. Nausea, vomiting and anorexia were classified using the Common Terminology Criteria for Adverse Events (CTCAE) ver4.0. Results A total of 23 and 29 patients were treated with ondansetron–dexamethasone (group 1) and palonosetron with dexamethasone–aprepitant (group 2), respectively. There was no significant difference in age, gender or the dose of cisplatin between the two groups. Patients in group 2 were more likely to achieve more favorable CINV control, e.g. a lower grade of nausea, vomiting or anorexia, lower incidence of rescue therapy required and shorter time to become CINV-free, than patients in group 1. Conclusions This study shows that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in UC patients treated with GC than ondansetron–dexamethasone.

The impact of 5HT3RA antiemetics on the incidence of chemotherapy-induced nausea and vomiting (CINV), treatment adherence, and delay of therapy in early-stage breast cancer (BC) patients treated with moderately/highly emetogenic chemotherapy (MEC/HEC).

75 Background: The effectiveness of 5-HT3receptor antagonists (5HTs) for the prevention of CINV is well established. Less is known about the impact of these drugs on chemotherapy adherence (AD) and preventing delayed therapy (DT). We examined the impact of palonosetron (PAL) vs. other 5HTs on CINV incidence, treatment AD and DT in early-stage BC. Methods: An observational nested case-control study was conducted using the HealthCore Integrated Research Database (HIRD). Female patients (pts) were identified by their first claim for IV MEC/HEC between 1/1/02 and 10/31/10 (index). Inclusion criteria were: ≥ 12 months health plan eligibility pre-index (baseline) and ≥ 6 months post-index (follow-up); ≥ 1 baseline claim for BC; no claim for secondary or multiple primary neoplasms; and ≥ 1 claim for 5HT during follow-up. CINV was defined using ICD-9 codes for nausea, vomiting, or related events, and use of rescue medications for 5 days after MEC/HEC. AD was defined as receiving the requisite number of cycles within the recommended NCCN timeframe. DT was defined as exceeding 2x the NCCN-recommended cycle length between MEC/HEC claims. Outcomes were assessed using descriptive analysis and multivariate logistic regression, controlling for demographics, baseline medical conditions, and index therapy. Results: We identified 682/696 [MEC] and 1,782/3,103 [HEC] pts who received PAL or other 5HTs, respectively. For PAL vs. 5HT, 33.7% vs. 49.7% (OR: 0.51; 95% CI 0.41-0.65; p&lt;0.01) had CINV (mean 0.27 vs. 0.61 events/cycle) in the MEC group; in the HEC group, 27.3% vs. 35.7% (OR: 0.61; 95% CI 0.53-0.7; p&lt;0.01) had CINV (mean 0.21 vs. 0.34 events/cycle). PAL users delayed MEC at a lower rate than those using other 5HTs (2.6% vs. 8.2%; OR: 0.37; CI 0.21-0.65; p&lt;0.01) but had similar AD (41.8% vs. 37.2%; OR: 1.2; CI 0.95-1.5; p=0.12). No differences in AD or DT were found among pts on HEC. Conclusions: Among early-stage BC pts initiating a MEC or HEC agent, PAL was associated with fewer CINV events, a lower (MEC) or equal (HEC) rate of delayed therapy, and equal adherence compared to other 5HTs.

Exploring Chemotherapy-Induced Toxicities through Multivariate Projection of Risk Factors: Prediction of Nausea and Vomiting

Many risk factors exist for chemotherapy-induced nausea and vomiting (CINV). This study utilized a multivariate projection technique to identify which risk factors were predictive of CINV in clinical practice. A single-centre, prospective, observational study was conducted from January 2007~July 2010 in Singapore. Patients were on highly (HECs) and moderately emetogenic chemotherapies with/without radiotherapy. Patient demographics and CINV risk factors were documented. Daily recording of CINV events was done using a standardized diary. Principal component (PC) analysis was performed to identify which risk factors could differentiate patients with and without CINV. A total of 710 patients were recruited. Majority were females (67%) and Chinese (84%). Five risk factors were potential CINV predictors: histories of alcohol drinking, chemotherapy-induced nausea, chemotherapy-induced vomiting, fatigue and gender. Period (ex-/current drinkers) and frequency of drinking (social/chronic drinkers) differentiated the CINV endpoints in patients on HECs and anthracycline-based, and XELOX regimens, respectively. Fatigue interference and severity were predictive of CINV in anthracycline-based populations, while the former was predictive in HEC and XELOX populations. PC analysis is a potential technique in analyzing clinical population data, and can provide clinicians with an insight as to what predictors to look out for in the clinical assessment of CINV. We hope that our results will increase the awareness among clinician-scientists regarding the usefulness of this technique in the analysis of clinical data, so that appropriate preventive measures can be taken to improve patients' quality of life.

Comparison of 1 mg/body and 3 mg/body of Intravenous Granisetron for the Prevention of Chemotherapy-induced Nausea and Vomiting and Adverse Events in Hematological Malignancy Patients

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.

Aprepitant for Patients Receiving Highly Emetogenic Chemotherapy: An Economic Analysis for Singapore

BackgroundAprepitant (a neurokinin 1 receptor antagonist), in combination with a serotonin receptor antagonist (5-HT3 RA) and dexamethasone, has demonstrated superior efficacy on end points related to chemotherapy-induced nausea and vomiting (CINV) compared with standard care (combination 5-HT3 RA and dexamethasone). ObjectiveTo determine the cost-effectiveness of an aprepitant-containing regimen compared with current clinical practice for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC) in Singapore. MethodsA decision-analytic model was constructed to assess the costs and outcomes associated with an aprepitant-containing regimen compared with standard care in the prevention of CINV following HEC. Three scenarios were modeled on the basis of results of four double-blind randomized clinical trials of aprepitant. CINV event probabilities were calculated on the basis of the occurrence of nausea and vomiting and the need for rescue medication in the 5 days following a single cycle of HEC. The analysis was conducted from the Singapore health care system perspective. ResultsAprepitant reduced emesis and nausea, resulting in small but clinically important improvements when measured in quality-adjusted life-years. The aprepitant-containing regimen was associated with higher acquisition costs but lower costs relating to patient management, hospitalization, and use of rescue medication. Across the scenarios, the incremental cost per emetic event avoided ranged from cost saving to Singapore $63 (US $51). The incremental cost-effectiveness ratio ranged from cost saving to Singapore $49,800 per quality-adjusted life-year gained (US $40,600). The analysis was relatively insensitive to changes in the inputs. ConclusionsAprepitant is a clinically important and cost-effective therapy for the prevention of CINV in patients treated with HEC in Singapore.