Functional Living Index-Emesis Research Articles

Analysis of Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting with Moderately and Highly Emetogenic Chemotherapy

This study aimed to determine how aprepitant affects the impact of chemotherapy-induced nausea and vomiting (CINV) on daily activities during highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Patients received aprepitant plus standard antiemetic therapy (ondansetron plus dexamethasone) or standard antiemetic therapy alone. Data were analyzed from pooled data of two Phase III randomized, double-blind HEC trials and one MEC trial. Patients completed the Functional Living Index-Emesis questionnaire. A significantly greater percentage of patients receiving aprepitant reported no or minimal CINV impact on daily life (overall total Functional Living Index-Emesis score >6) compared with those receiving standard therapy alone (HEC: 74.4 vs 63.9%, respectively; p < 0.01; MEC: 73.4 vs 66.3%; p < 0.05). In HEC, favorable responses to aprepitant treatment persisted in nausea (70.2 vs 60.9%) and vomiting domains (84.6 vs 68.7%; both p < 0.01). Similar results were seen in MEC. Addition of aprepitant reduced CINV impact on daily life compared with standard antiemetic therapy.

A Study of Chemotherapy-induced Nausea and Vomiting Involving Different Dosage Regimens of Cisplatin

Objective To compare fractionated doses cisplatin(DDP)with single high-dose cisplatin on reducing Chemotherapy-induced nausea and vomiting(CINV)and improving patients' living function.Methods From October 2011 to June 2012,101cases treated by combined chemotherapy with cisplatin were divided into two groups by different ways of DDP treatment,Group A:DDP 75mg/m2,iv drip,d1;Group B:DDP 25mg/m2,iv drip,d1-3.Patients diary recorded episodes of CINV two times during each cycle on day 2(24hours after chemotherapy administration)and on day 6.In addition,all patients completed a functional living index-emesis(FLIE)questionnaire,on day 6,each cycle for two circles.Results In acute phase the remission rate of nausea and vomiting were 69.4%,77.6%in Group A and more decreased than 88.5%,92.3%in Group B,respectively(P0.05).In delayed phase the remissions of nausea and vomiting were 32.7%,55.1% in Group A and higher compared with 34.6%,71.2%in Group B(P0.05).Based on the FLIE assessment,the patients of reduced daily function was 46.9%in group A,and similar to 28.7% in Group B(P0.05).Conclusion Compared with DDP of single high-dose,DDP of fractionated doses could reduce the prevalence of CINV in acute phase,but in delayed phase.And there is no difference of influence on patients' living function between the two ways.

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly or Moderately Emetogenic Chemotherapy: A Randomized, Double-Blind, Placebo-Controlled Study

ContextChemotherapy-induced nausea and vomiting (CINV) can severely impair patients' quality of life (QOL). Psychotropics, especially olanzapine, have a strong antiemetic effect. ObjectivesTo determine whether olanzapine could reduce the frequency of CINV and improve patients' QOL during chemotherapy. MethodsThis was a randomized, double-blind, placebo-controlled trial. Forty-four patients scheduled to receive highly or moderately emetogenic chemotherapy were enrolled. All patients received a 5-hydroxytryptamine3 receptor antagonist, steroid, and neurokinin-1 receptor antagonist. Patients were randomly assigned to take 5 mg/day of oral olanzapine (OL group, n = 22) or placebo (control group, n = 22) daily from the day before chemotherapy (Day 0) to Day 5. The primary endpoint was the rate of patients who achieved total control (no vomiting, no use of rescue medications, and maximum nausea of <5/100mm on a visual analogue scale). The secondary endpoint was Functional Living Index-Emesis questionnaire score on Days 0 and 6. ResultsThe rate of patients achieving total control was significantly higher in the OL group (86% and 64% in acute and delayed phases, respectively) than in the control group (55% and 23%, P = 0.045, P = 0.014, respectively). Furthermore, the OL group experienced a better QOL than the control group, as reported on the Functional Living Index-Emesis questionnaire (P = 0.0004). ConclusionThe addition of 5mg/day of oral olanzapine to standard therapy can reduce the frequency of CINV and improve QOL of patients receiving highly or moderately emetogenic chemotherapy.

Does gabapentin prevent delayed chemotherapy-induced nausea and vomiting (N/V)? Results of a randomized placebo controlled trial, NCCTG N08C3 (Alliance).

9513 Background: The need for more research in N/V control is exemplified by agents that are costly, interfere with cytochrome P450 metabolism, and inadequately address delayed N/V. Based on pilot data, there was justification for evaluating whether gabapentin could improve the prevention of delayed N/V from highly emetogenic chemotherapy (HEC). Methods: Patients (pts) about to receive HEC were randomized to prophylactic treatment with 20 mg of dexamethasone (dex) and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by either gabapentin (gaba) 300 mg BID and dex or placebo (plac) and dex. Gaba/plac was started the evening of the day of chemotherapy and continued through day 5 of the first chemotherapy cycle. Dex was given at 8 mg BID days 2-3, then 4 mg BID for day 4, in both arms. The primary endpoint was complete response (CR), defined as no emesis and no rescue medications day 2-6, using a nausea and vomiting diary. The percent of CR were compared in each group by Fisher’s exact test. Secondary outcomes included the Functional Living Index-Emesis (FLIE), satisfaction, and a side effect questionnaire. Results: 430 pts were enrolled in this study between 5/2009 and 2/2011. 47% of pts in the gaba arm and 41% in the plac arm had a CR (p=.23). At some time during days 2-6, 30% in the gaba and plac arms experienced emesis, and 45% and 53% in the gaba and plac arms, respectively, took rescue medication. Mean diary nausea scores over days 2-6 ranged from 0.9 – 1.2 (gaba arm) and 1.0-1.3 (plac arm)(7 = the worst); mean number of diary emetic episodes ranged from 0.1 -0.3 (gaba arm) and 0.1-0.2 (plac arm). The FLIE was not significantly different between arms. Mean vomiting satisfaction was 9.1 in both arms and for nausea was 8.3 for gaba, 8.1 for plac (10= totally satisfied). There were no significant differences in toxicities by CTCAE provider grading or by self-report. Conclusions: In this study, gaba did not improve delayed N/V. Overall, there was little emesis and nausea severity was low. Patients were satisfied with the control of their N/V, irrespective of arm. The use of standard prophylactic guidelines that include a 5HT3RA and dex provided good control of N/V for most patients. Clinical trial information: NCT00880191.

Carbamazepine for the prevention of chemotherapy-induced nausea and vomiting: A pilot study using the Simon's optimal two-stage design.

e20699 Background: Nausea and vomiting have been a major drawback to patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of patients. Because of its high cost, this treatment is unavailable in centers where health assistance is provided by the government. As an effort to ameliorate prevention of CINV at lower costs, we studied the efficacy of the addition of carbamazepine to a regimen of corticosteroid plus 5-hidroxitriptamine-3 receptor antagonist for prevention of CINV as well as its side effects and influence on patients’ quality of life. Methods: This is a prospective open label phase II nonrandomized study carried out in a Brazilian public Oncology service. Patients scheduled to receive the first cycle of highly emetogenic chemotherapy were continuously recruited. Besides the current standard antiemetic treatment, patients received carbamazepine, p.o., according to the following schedule: 200 mg QD on the third day before chemotherapy; 200 mg BID on the second day before chemotherapy; 200 mg TID from one day before until the fifth day after chemotherapy. Considering sparse evidence about the anticonvulsants’ efficacy in CINV prevention, we adopted Simon’s optimal two-stage design which should include 43 patients unless overall complete prevention was not achieved in 9 out of the first 15 entries. Functional Living Index-Emesis (FLIE) questionnaire was used to measure impact on quality of life. Results: None of ten studied patients (0%) had overall complete prevention and nine needed rescue medication. Three quitted carbamazepine therapy because of somnolence and vomiting before chemotherapy infusion. Seven were able to take medication for the entire period and none were responsive, so the study was closed. There was no impact on patients´ quality of life. Conclusions: Carbamazepine was not effective for prevention of CINV and should not be used for this purpose out of experimental settings. The Simon optimal design allowed us to reach this data and stop the trial for futility, minimising the number of patients possibly exposed to an inactive agent.

Comparison of yoga versus relaxation on chemotherapy-induced nausea and vomiting (CINV) outcomes a mechanism of action study.

6624 Background: Chemotherapy induced nausea and vomiting is a common distressing symptom. In this study we evaluated the effects of Yoga vs. Jacobson’s relaxation training on CINV outcomes in chemotherapy naive patients undergoing moderately to highly emetogenic chemotherapy. Methods: One hundred and twenty patients who satisfied the selection criteria and gave written consent to participate were randomized to receive Yoga or Jacobson’s relaxation or serve as waitlist controls for first 4 cycles of chemotherapy. Assessments for nausea and emesis including functional living index emesis, nausea diary and cardiac autonomic function and electrogastrogram were carried out at baseline, six days after 1st cycle, after 2nd and 3rd cycle of chemotherapy. Assessments for mood states such as anxiety and depression using HADS, and perceived stress were carried out at baseline and after 3rd cycle of chemotherapy. Both interventions were for a duration of 25 minutes imparted by a trained instructor. Data were analysed using repeated measures ANOVA with post hoc Bonferroni tests. Results: There was a significant decrease in acute and delayed nausea severity in Yoga compared to control group (p=0.001) and Jacobson’s group (p=0.004) after 1st cycle of chemotherapy. There was a significant decrease in self reported anxiety and depression in Yoga (p=0.03) and Jacobson’s relaxation (p=0.004) compared to control group following 3rd cycle of chemotherapy.There was significant decrease in LF/HF ratio in Yoga group compared to control group (p=0.06) after 3rd cycle of chemotherapy. There was a significant decrease in bradygastria (p=0.002) and tachygastria percentage (p=0.03) in Yoga group compared to Jacobson’s and control group becoming more evident after 3rd cycle of chemotherapy. Conclusions: Both Yoga and Jacobson’s intervention conferred beneficial effects in reducing chemotherapy induced nausea and vomiting. Yoga helps normalise gastric motility and enhances cardiac and gastric parasympathetic activity in subjects undergoing chemotherapy. Clinical trial information: NCT01387841.

Evaluation of the efficacy of aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life with functional living index emesis.

Functional Living Index Emesis (FLIE) is developed to evaluate the relationship between emesis and it's effects on patient's daily life and is far more relevant to detect the effectiveness of antiemetic treatment compared with self-diary reports. In this study, the efficacy of oral neurokinin-1 antagonist aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life is evaluated with FLIE. Cross sectional study. Sixty patients with Non-Small Cell Lung Cancer (NSCLC) receiving a chemotherapy regimen consisting of Cisplatin and Docetaxel were evaluated. The patients were prospectively randomized to two groups before the first cycle of chemotherapy. Patients in Group A (31 patients) received 3 daily doses of aprepitant along with oral ondansetron and dexamethasone. The patients in group B (29 patients) received only ondansetron and dexamathasone. The efficacy of both regimens was evaluated by a modified Turkish version of FLIE scale consisting of 18 questions. The number of patients with complete response was 31 in the whole group. Of these 18 patients (58%) were in Group A (Aprepitant) and 13 patients in group B (42%). Median FLIE score in group A was 24.97 (±12.45) while it was 38.1 (±26.987) in group B and the difference was statistically significant (p=0.022). Total score >20 was seen in only 5 of 31 patients in aprepitant group (16%) showing the significant efficiency of aprepitant on quality of life, while in group B, 13 of 29 patients (44%) had total scores >20 (p=0.02). Regarding these findings, it is certain to state that aprepitant in combination with other drugs optimizes protection against both nausea and vomiting compared to the prior standard of care, and must be recommended as first-line therapy for patients who are treated with moderately or highly emetogenic chemotherapy.

Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

A Randomized Double Blind Study to Evaluate Efficacy of Palonosetron With Dexamethasone Versus Palonosetron Alone for Prevention of Postoperative and Postdischarge Nausea and Vomiting in Subjects Undergoing Laparoscopic Surgeries with High Emetogenic Risk

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common occurrences (50%-80%) after laparoscopic surgery. Palonosetron (Pal), the newest 5-HT3 antagonist, is an effective antiemetic that has advantages in treating PDNV due to its prolonged duration of action. We hypothesized that a combination of Pal and dexamethazone (Dex) could further improve the efficacy of the treatment in comparison to Pal alone in patients at high risk for PONV. Patients scheduled to undergo laparoscopic surgeries under general anesthesia were randomized to receive 8-mg dexamethasone + 0.075-mg palonosetron (Pal + Dex) or an equivalent volume of saline + 0.075 mg palonosetron (Pal). Data was collected at defined postoperative times (2, 6, 12, 24, and 72 hours). All patients also completed an 18-question QOL-Functional Living Index-Emesis instrument at 96 hours. We enrolled 118 patients, ASA 1-2, with at least 3 PONV risk factors, who were undergoing outpatient surgery. Both groups had a low incidence of vomiting in the PACU (Pal + Dex, 1.7%; Pal, 6.8%) and at 72 hours (0.0% both groups). Complete response (no vomiting, no rescue medication) was not different between treatment groups for any time intervals. Cumulative success rates over the entire 72 hours were 60.4% (Pal + Dex) versus 60.0% (Pal). The Pal + Dex group showed a trend toward greater satisfaction on the QOL- Functional Living Index-Emesis scores with the greatest differences in the "nausea domain". The combination therapy of palonosetron + dexamethasone did not reduce the incidence of PONV or PDNV when compared with palonosetron alone. There was no change in comparative efficacy over 72 hours, most likely due to the low incidence of PDNV in both groups.

Effects of Aprepitant on Drug Metabolism in Lymphoma Patients Receiving Multi-Day Chemotherapy Regimen of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, + Rituxan (R/CHOP): Randomized, Cross-Over Study

Abstract 1613Chemotherapy-induced nausea and vomiting (CINV) is a frequent adverse event that can impair the quality of life in cancer patients (pts). In pts receiving cyclophosphamide (CP) and doxorubicin-based regimen, the combination of dexamethasone (dexa) and 5-HT3 receptor antagonists (5-HT3 RA) is very effective in acute emesis, however, control of delayed-emesis remains poor. The neurotransmitter substance P appears to be involved in both the acute and delayed-phases. Aprepitant, a substance P/ neurokinin (NK)-1 receptor antagonist, when combined with 5-HT3 RA and dexa, has been shown to prevent acute and delayed CINV associated with moderately and highly emetogenic chemotherapy (CT). However, aprepitant is a moderate inhibitor of cytochrome p-450 system, primarily via CYP 3A4, a liver microsome that also metabolizes several CT agents, including CP to some extent, its use has been approached with caution. This study evaluated the effect of aprepitant on drug metabolism in lymphoma pts receiving (R)CHOP which contains several agents that can be affected by this pathway. This randomized, cross-over trial was designed to enroll 18 evaluable pts; the absence of pharmacokinetic (PK) drug interactions can be determined if the 90% confidence interval (CI) of the geometric mean AUC ratio between 2 groups is within 80 to 125%. All pts received standard anti-emetic regimen of 5-HT3 RA (ondansetron) and steroids. The pts were randomized into 2 groups. Group 1 received aprepitant in cycle-1 and not in cycle-2. Group 2 received aprepitant in cycle-2 and not in cycle-1. The cross-over design was used to minimize inter-patient PK variability and drug cumulative effects, by using the patients as their own control. For breakthrough N/V, medications that are substrates, inducers, or inhibitors of CYP 3A4 were not permitted. Blood samples were drawn during and post CT infusion in both groups at following time points: baseline before the start of treatment, 30, 60, 75, and 90 minutes, and 2, 4, 6, 8, and 24 hours from the start of CP infusion. Samples were analyzed for concentration of CP, vincristine, and prednisone, and their active metabolites. Eighteen of the 23 pts enrolled completed 2 cycles and were evaluable for PK analysis. Both groups were comparable with regards to demographics. The data for AUC for parent drug and metabolites are shown below.Geometric Mean AUC 0–24hr [(μg/mL*hr)/mL]Ratio of Geometric Mean AUC 0–24hr Analyte in Aprepitant Treatment to Control (90% CI)AprepitantControl1.20 (1.08–1.33)CP300.0250.52-deCl-CP4.560.75 (0.65–0.86)4-OH-CP3.940.97 (0.83–1.13)PR€2872651.08 (1.02–1.15)PL€441638171.16 (1.01–1.32)VC€41391.04 (0.82–1.33)€(ng/mL*hr) Abbreviations: CP, Cyclophosphamide; 2-deCl-CP, 2-dechloro-cyclophosphamide; 4-OH-CP, 4-hydroxy-cyclophosphamde, PR; prednisone, PL; prednisolone, VC; vincristineThe AUC for active metabolite (4-OH-CP) was within the pre-defined range; but there was some increase in the parent CP and some decrease in the toxic metabolite (2-deCl-CP). The AUC for PR was within the defined range. Although, there was some increase in the active metabolite PL, the blood sugar levels were not significantly different in 2 groups (mean change 43% vs 37%). The Functional Living Index-Emesis (FLIE) scores for N/V were not significantly different. There were no serious adverse events related to aprepitant. Conclusions:Administration of aprepitant with (R)CHOP resulted in minor changes in the levels of parent drugs and/or metabolites; which are unlikely to have significant clinical impact. Disclosures:Vadhan-Raj:Merck: Research Funding. Spasojevic:Merck: Research Funding. Neelapu:celgene: Research Funding.

Measurement of Postdischarge Nausea and Vomiting for Ambulatory Surgery Patients: A Critical Review and Analysis

Approximately one-third of patients experience nausea and vomiting after discharge from ambulatory surgery settings, yet there have been no clear and definitive instruments used to measure it. A critical review and analysis of the measurement of postdischarge nausea and vomiting was conducted. Twenty-eight articles met the inclusion criteria. Four studies (14.3%) used instruments with documented reliability and validity. Telephone calls were used in 21 (76%) studies to interview patients, and seven studies (25%) used a mail-in investigator-developed diary or questionnaire. Most studies (22) obtained data at 48 hours; 13 of those obtained data exclusively at 24 hours. Definitions, measurement, and clinical outcomes were defined differently in each study. Of the instruments examined, the Ambulatory Surgery Inventory of Nausea, Vomiting, and Retching and Functional Living Index-Emesis provide the possibility for outcome standardization. Although both instruments possess strengths, more study is needed to advance the measurement of nausea and vomiting in the postdischarge ambulatory surgery patient.

Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study

BackgroundChemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. This study investigated: (1) the impact of CINV on patients' health-related quality of life (HRQL) in daily clinical practice; (2) the association between patient characteristics and type of antiemetics and CINV; and (3) the role of CINV in physicians' decisions to modify antiemetic treatment.Patients and methodsThis prospective, multicenter study was conducted in nine general hospitals in the Netherlands. During three consecutive chemotherapy cycles, patients used a diary to record episodes of nausea, vomiting and antiemetic use. For each cycle, these ratings were made 1 day prior to and 7 days after having received chemotherapy. The influence of CINV on patients' HRQL was evaluated with the Functional Living Index-Emesis (FLIE) questionnaire at day 6 of each treatment cycle. (Changes in) antiemetic use were recorded by the treating nurse. Patient inclusion took place between May 2005 and May 2007.ResultsTwo hundred seventy-seven patients were enrolled in the study. Acute and delayed nausea during the first treatment cycle was reported by 39% and 68% of the patients, respectively. The comparable figures for acute and delayed vomiting were 12% and 23%. During the first and subsequent treatment cycle, approximately one-third of the patients indicated that CINV had a substantial impact on their daily lives. Female patients and younger patients reported significantly more CINV than male and older patients. At all treatment cycles, patients receiving treatment with moderately emetogenic chemotherapy, containing anthracycline, reported more acute nausea than patients receiving highly emetogenic chemotherapy. Acute vomiting was associated significantly with change in (i.e., additional) antiemetic treatment. Delayed CINV did not influence antiemetic treatment.ConclusionCINV continues to be a problem that adversely affects the daily lives of patients. CINV is worse in women and in younger patients. In daily clinical practice, acute CINV, but not delayed CINV, results in changes in antiemetic treatment. In view of the effects of not only acute, but also delayed CINV on daily life, more attention should be paid to adjustment of antiemetic treatment to cover CINV complaints, later during the chemotherapy cycle.

Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a US population

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of chemotherapy, but it may be prevented or mitigated with medications. Uncontrolled CINV can lead to reduced quality of life and can result in increased costs (due to health care utilization and missed work). We prospectively assessed the prevalence and burden of CINV in a US population. Final analysis was performed on 178 patients, beginning chemotherapy during 2007-2008 at oncology specialty settings. Patients kept a diary recording use of antiemetic medications just before the start of chemotherapy and use of antiemetic medications, health care resources, and episodes of nausea and vomiting during the 5days following. In addition, they completed a Functional Living Index-Emesis (FLIE) questionnaire and a Work Productivity and Assessment Inventory-Nausea and Vomiting assessment, to determine the impact of CINV on daily functioning and on work productivity, respectively. Physicians independently recorded prescribed medications and health care utilization. Of the patients, 61.2% reported experiencing CINV (34.3% with acute CINV and 58.4% with delayed CINV). Based on the FLIE assessment, 37.2% of all patients reported reduced daily functioning, and of those with poorly managed CINV, about 90% reported a significant impact on daily functioning. Total costs due to CINV were on average $778.58 per patient from the day of administration through the 5days following the first cycle of chemotherapy; patients with more severe CINV typically had higher costs. CINV remains a significant problem among US patients, suggesting a need for more effective prophylaxis use in clinical practice.

A prospective study on the incidence of delayed nausea and vomiting following administration of carboplatin-containing regimens for treatment of cancer without prophylactic aprepitant.

e19552 Background: Delayed nausea and vomiting following administration of carboplatin-containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis (a 5-HT3 antagonist and dexamethasone). Methods: We report results of a prospective study to evaluate the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) after the first cycle of treatment. Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing regimen (AUC 5 or above) (but no prophylactic aprepitant) were eligible to participate. Primary endpoint is the incidence of CINV after cycle 1 of chemotherapy. Secondary endpoints include the incidence of CINV after the third cycle and the gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24-48 hours following chemotherapy to assess the severity and need for breakthrough medications for CINV. Results: The characteristics of 109 patients enrolled: 58% male, mean age 63.9 years (range 42-82 years) and 85% diagnosed with lung cancer. Twenty-two percent of patients reported moderate to severe CINV 72 hours after chemotherapy, with symptoms persisting as long as 96 hours in 23% of the patients after cycle 1. Multivariate analysis was performed to evaluate the association between gender and the incidence of CINV. There was no statistically significant difference in gender (p = 0.43) or between cycle 1 and cycle 3 (p = 0.19). Conclusions: Without prophylactic aprepitant administration, one-fifth of cancer patients receiving carboplatin containing regimen had moderate to severe delayed CINV. Percentage of patients with delayed CINV 24 hrs 48 hrs 72 hrs 96 hrs Cycle 1 9.71% 13.73% 21.78% 22.77% Cycle 3 4.00% 12.77% 14.58% 16.00% No significant financial relationships to disclose.

Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy

The control of chemotherapy-induced nausea and vomiting (CINV) is critical in preventing poor health outcomes and increasing patient quality of life. The objective of this study was to evaluate the impact of the addition of casopitant to dual-combination therapy of dexamethasone and ondansetron on quality of life in patients receiving highly emetogenic chemotherapy (HEC). In a multicenter, double-blind, randomized, placebo-controlled, add-on trial (N = 810), patients were randomized to intravenous (IV) ondansetron/dexamethasone alone (control) or in combination with either a single 150-mg oral dose of casopitant or 3-day IV/oral casopitant. Quality of life was assessed as impact of nausea and vomiting on daily life using the Functional Living Index Emesis (FLIE) questionnaire. Patients completed the FLIE questionnaire at baseline prior to receiving chemotherapy and after completion of the first cycle of HEC. Patients in the single oral dose and 3-day IV/oral casopitant groups scored higher mean total FLIE scores (115.7 and 114.0, respectively; p ≤ 0.0332) than patients in the control group (107.5), indicating that casopitant patients experienced less impact from nausea and vomiting on daily life. The overall absolute difference in the proportion of patients reporting CINV with no impact on daily life between the single oral casopitant group and the control group was 13%; the difference between the 3-day IV/oral casopitant group and the control group was 14%. The addition of casopitant to ondansetron and dexamethasone in patients receiving HEC was significantly more effective in reducing the impact of nausea and vomiting on all daily life activities as assessed by the FLIE compared with ondansetron/dexamethasone dual therapy.

3029 The dosing frequency of sustained-release opioids and the prevalence of end-of-dose failure in cancer pain control: a Korean multicenter study

Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index—Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). Cisplatin-treated patients in a double-blind randomised trial received either aprepitant+dexamethasone+ondansetron on day 1 and aprepitant+dexamethasone on days 2–5 or standard antiemetic therapy (dexamethasone and ondansetron on day 1 and dexamethasone on days 2–5). Emetic events, nausea ratings and rescue medications were recorded in a 5-day diary and the FLIE was completed on day 6. Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients’ daily lives.

Can adjuvant homeopathy improve the control of post-chemotherapy emesis in breast cancer patients? Results of a randomized placebo-controlled trial

e20566 Background: Homeopathy used as an adjunct in the treatment of chemotherapy (CT)-induced emesis has rarely been evaluated. Methods: Patients with non-metastatic breast cancer treated with 6 courses of FAC 50, FEC 100 or TAC chemotherapy were randomized to Cocculus/nux vomica/tabacum/petroleum extract (Cocculine, C) or Placebo (P) in a multicentric comparative double-blind phase III study. Anti-emetic treatment was standardized (corticoids + ondansetron). Patients were evaluated after each course. The primary endpoint was nausea measured after the 1st CT course using the FLIE (Functional Living Index for Emesis) with 5-day recall. The planned sample size was 396 evaluable patients based on a minimum expected difference in mean of 0.5 ± 1.6 on a scale from 1 (a lot) to 7 (not at all) with 5% two-sided α error and 85% power. An intent-to-treat analysis was planned. Secondary evaluation criteria were: vomiting measured by the FLIE score, patient self-evaluation (EVA) and investigator recording (NCI-CTC) of nausea and vomiting intensities, and compliance. Results: From September 05 to January 08, 431 patients were randomized (217 to P and 214 to C). Patient characteristics were well balanced between groups. Median age was 53 years, 35% of the patients experienced nausea or vomiting. In total, 403 patients (93.5%) were assessable for the primary endpoint, with few nausea episodes (FLIE nausea scores after the 1st CT course were 6.02 and 6.07 for P and C, respectively) and very good compliance (81% patients complied with the protocol). Adverse events related to nausea occurred in 51% vs. 47% of the patients treated with P and C, respectively (p = 0.48). FLIE and NCI-CTC vomiting scores were similar between the 2 arms (6.91 vs. 6.88, p = 0.47, and 20% vs. 21%, p = 0.73, for P and C, respectively). Grade II-III nausea occurred in 17.6% and 15.7% of patients receiving P and C (p = 0.62). Conclusions: No benefit of homeopathy over standard treatment was noted in this study. But surprisingly we observed lower rates of nausea and vomiting measured by patients and by investigators, than in other studies using identical chemotherapy regimens. The observation and management of emesis could modify the perception and rate of such adverse events. No significant financial relationships to disclose.

Evaluation of nausea and vomiting in melanoma patients treated with consecutive days of cisplatin

e20702 Background: Chemotherapy-related nausea and vomiting (N/V) continue to be significant problems for cancer patients. In order to properly design a study leading to control of N/V in patients receiving consecutive days of cisplatin, stage IV melanoma patients who received three consecutive days of a cisplatin-containing chemotherapy were assessed. Methods: Patients were treated with cisplatin (25mg/m2, days 1–3), DTIC (220mg/m2, days 1–3), BCNU (150mg/m2, day 1) and tamoxifen (20mg twice a day, consecutively). The second cycle was given in 4 weeks without BCNU. Appropriate antiemetics were given during chemotherapy and then as needed for symptom control. N/V were assessed with the Functional Living Index-Emesis (FLIE) questionnaire for seven days (days 1–7). The median intensity of N/V during the early phase (days 1–3) and the late phase (days 4–7) was analyzed using the linear mixed effects model, adjusting for the subject random effects. The rates of intractable N/V (total FLIE score equal or less than 108) were analyzed in the random-effects logistic regression model. Results: A total of 14 patients answered the FLIE questionnaire. For nausea in cycle 1, the means of the median FLIE scores were similar in the early (52.7, 95%CI: 44.5, 60.8) and late (50.2, 95%CI: 42.0, 58.3) phases. In cycle 2, lower scores were observed in the late phase (45.2, 95%CI: 36.4, 54.0) than in the early phase (54.1, 95%CI: 45.6, 62.7) with a significant difference of 8.9 points (95%CI: 0.1, 17.7, p=0.049). For vomiting, the means of the median FLIE scores were similar in the early and late phases of either cycle. For the rates of intractable N/V, the differences between cycles and late vs. early phases were borderline significant. Higher odds of intractable N/V were estimated for cycle 2 vs. cycle 1 [OR=2.44 (95%CI: 0.945, 6.29; p=0.065)] and for late vs. early phases [odds ratio OR=2.39 (95%CI: 0.970, 5.870; p=0.058)]. Conclusions: The FLIE questionnaire is useful for objective assessment of N/V in patients who receive consecutive days of emetogenic chemotherapy. The data obtained from this study will form the basis for a future interventional study in which anti-emetics that are effective for late-phase N/V will be tested. No significant financial relationships to disclose.

Prospective evaluation of incidence and pattern of nausea in patients receiving combined chemotherapy and radiotherapy (RT) above the diaphragm

e20676 Background: Nausea (N), vomiting (V) remain distressing effects of chemotherapy. Prevalence of N, V in patients (pts) receiving daily (5/7) RT with weekly (wkly) doublet chemotherapy is not well studied. Methods: We used a modified Functional Living Index Emesis (FLIE) (Lindley and Mullin) to study N, V in pts receiving 2 chemotherapy agents with RT for upper aero-digestive malignancies. Exclusion criteria were: other causes of N,V or RT below the diaphragm. Pts completed a written questionnaire wkly during therapy. A 6 point scale was used, 0 representing no symptoms and 6 representing intolerable or uncontrolled symptoms. Questions addressed N, V, use of medication in daily diary and overall wkly assessment of N, V, ability to eat, effectiveness of medications and effect on daily routine. Results: 21 Patients enrolled: 15 completed 4 weekly questionnaires, 17 completed 3. Most patients received a total of 5 weekly chemotherapy treatments. Participants: 17 M: 4 F with 17 head/neck sites, 4 lung. 6 pts received wkly carboplatin (AUC 2) and paclitaxel (45/m2 for lung, 30/m2 for h/n); 15 pts cisplatin (20/m2) and paclitaxel. All patients received our standard anti emetic therapy (steroids and 5 HT3 receptor antagonist). Pts with early nausea tended to experience continued or worsened symptoms despite anti emetic therapy; at wk 4, more pts experienced V. Selected results are shown in the table . Conclusions: The modified FLIE questionnaire was a useful tool for evaluation. Despite advances in anti emetic therapy, nausea and vomiting resulting from the combination of radiation therapy with dual agent chemotherapy exerts a significant adverse effect on daily comfort but little effect on overall function. [Table: see text] [Table: see text]

Oxaliplatin for colorectal cancer: Prevalence of delayed nausea and/or vomiting

e20610 Background: Delayed nausea and vomiting (N&amp;V) have been associated with cisplatin and carboplatin. Its prevalence with third-generation oxaliplatin was examined in patients (pts) receiving oxaliplatin-based regimens. Methods: 64 pts (53% male, 47% female) signed IRB-approved informed consent and were enrolled on day 1 of cycle 1. 53 (83%) pts had colon cancer, and received 85mg/kg of oxaliplatin, while 11 (17%) had rectal cancer, and received 65mg/kg. Age ranged from 29 to 84 years, with 65% between 50 and 69. Data was collected on the first chemotherapy cycle of 24 pts and the first and second cycles of 40 pts, for a total of 104 cycles. Baseline demographic data were collected by chart review and interview. Maximum grade of N&amp;V for each cycle was assessed by the Functional Living Index - Emesis (FLIE). Pts also maintained a daily diary of nausea, vomiting, and anti-emetic usage for 7 days after each infusion. Results: 7 pts (11%) reported a history of motion sickness. History of morning sickness was reported by 13 (43%) of the 30 female pts. All pts received anti-emetics and steroids on day 1 of each cycle. 75% of pts received 5HT3 inhibitors only, 22% received 5HT3 + an oral NK-1 receptor antagonist, and 3% received an NK-1 receptor antagonist alone. Among 40 pts for whom data were collected on both first and second cycles, the occurrence of nausea was the same during cycle 1 and cycle 2: Grade 0 - 60% and 62% respectively; Grade 1 - 20% and 21%, Grade 2 - 20% and 21%. 41% of pts used rescue antiemetics (prochlorperazine, metoclopramide, or lorazepam) in cycle 1 and 43% in cycle 2. Men experienced no nausea 69% of the time, while women had no nausea in 41% of cycles. In 57% of cycles, no nausea was reported. In 88% of cycles there was no reported vomiting. Conclusions: Oxaliplatin-based regimens (65–85 mg/kg) caused minimal nausea and negligible vomiting, with a satisfactory response to 5HT3-inhibitor antiemetics and corticosteroids. [Table: see text] [Table: see text]