Functional Living Index-Emesis Research Articles

Results of an Open-Label Study to Evaluate the Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated with Carboplatin-Containing Chemotherapy in Patients with Ovarian Cancer, Primary Peritoneal, or Fallopian Tube Carcinoma (Stage I-IV) or Papillary Serous Cancer of the Uterus

PurposeAprepitant might offer an advantage in preventing acute/delayed chemotherapy-induced nausea and vomiting (CINV). This study integrated palonosetron and dexamethasone into the regimen to determine the efficacy and safety of this combination. Patients and MethodsFifty patients were enrolled; 49 were evaluable. Main inclusion criteria were (1) diagnosis of ovarian (OV), primary peritoneal (PP), or fallopian tube (FT) carcinoma (stage I-IV) or papillary serous cancer of the uterus (UPSC); (2) patients naive to emetogenic chemotherapy Hesketh ≥ level 4; (3) scheduled to receive paclitaxel 175 mg/m2 intravenously (I.V.) and carboplatin AUC 6 I.V.; able to read/understand the Functional Living Index–Emesis questionnaire. ResultsMedian age was 61 years, 60% had Eastern Cooperative Oncology Group performance status of 0, 86% had previous surgery (74% OV, 12% PP, 8% UPSC, and 6% FT). The metastases rate was 30%; 21% were visceral metastasis. Eighty-six percent of patients reported no vomiting or use of rescue medications during cycle 1 (95% and 100% in cycles 2–3 and 4–6, respectively) and were deemed as complete responders. Grade 3/4 treatment-related adverse events limited to neutropenia (6%). Grade 1/2 toxicities > 5% included nausea (12%), alopecia, constipation, arthralgia (8% each), and anemia (6%). Some toxicities might have been related to chemotherapy and were not related to the aprepitant, palonosetron, or dexamethasone. ConclusionThe addition of aprepitant to palonosetron and dexamethasone appears to be very well tolerated. This combination is effective in the prevention of chemotherapy-induced nausea and vomiting when used with emetogenic therapy (paclitaxel and carboplatin).

Adapting ASCO and NCCN guidelines in institutional antiemetic guidelines benefits patients receiving chemotherapy

20508 Background: The primary endpoint of the present study was to determine the impact of adapting ASCO and NCCN guidelines for antiemetics (AE) in our institutional antiemetic guidelines. Methods: The emetic risk of chemotherapy regimens was calculated using the Hesketh classification. AE guidelines were adapted and approved by a multidisciplinary team and the Drugs and Therapeutics Committee. We have compared 2 groups: patients receiving the new adapted institutional AE with those receiving non-established antiemetic treatment. Patients recorded episodes of nausea and vomiting in a diary the day of chemotherapy administration and the following 4 days. Patients also recorded rescue antiemetic medications. Patients completed the Functional Living Index- Emesis (FLIE) questionnaire at baseline and on day 6. The FLIE total scores >108 was defined as ‘no impact on daily functional‘. The main updates of the new adapted AE guidelines included the addition of aprepitant in cisplatin-based schedules, granisetron dose of 1 mg instead of 3 mg or ondansetron and dexametasone dose based on the emetic potential of each chemotherapy protocol. A delayed antiemetic protocol was recommended for each chemotherapy protocol. Results: From February 2007 to August 2007 225 consecutive patients were prospectively included in the study, 119 patients before the implementation of new AE guidelines and 106 patients after. Patients receiving the new AE guidelines achieved a trend for more complete response (defined as no nausea, no vomiting and no AE rescue): 52% vs 66.7% (p=0.065). In the cisplatin-based group, patients receiving the new AE guidelines obtained a statistically significant benefit with the new protocol (47.6% vs 73.3 % [p=0.017]), and less patients presented a reduction in the FLIE score below 108 (42 % vs 24% [p=0.142]). Conclusions: Implementation of revised AE guidelines provides a better control of CINV with higher complete response rate, especially in patients receiving cisplatin-based schedules. No significant financial relationships to disclose.

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

20626 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 & dexamethasone). Methods: We report here preliminary results of an ongoing 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) are 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 & 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 & need for breakthrough medications for CINV. Results: The characteristics of 50 patients enrolled thus far: 54% male, mean age 63.2 years (range 42.2 - 79.6 years) and 86% diagnosed with lung cancer. Thirty six percent of patients reported moderate to severe CINV 72 hours after chemotherapy, with symptoms persisting as long as 96 hours in 33% of the patients after cycle 1. Women had only a slightly higher incidence of CINV (38%) than men (35%) at 72 hours following cycle 1, but a significantly higher incidence of emesis was seen in women (31%) compared to men (8%) (P=0.047) at 72 hours following cycle 3. Conclusions: Without prophylactic aprepitant administration, one third 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 13.51% 24.32% 36.11% 33.34% Cycle 3 3.85% 21.74% 20.00% 23.08% No significant financial relationships to disclose.

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy

This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Pilot study of dronabinol for adult patients with primary malignant gliomas

19607 Background: Chemotherapy-induced nausea and vomiting (CINV) are common adverse effects from chemotherapy. While most treatments administered in patients with primary gliomas are not highly emetogenic, up to 50% of neuro-oncology patients report CINV despite 5HT3 or steroid therapies. Adjuvant benzodiazepines frequently alter mental status. Dronabinol may provide a safe alternative option without compromise of neurological status. his study seeks to describe toxicities (TOX) associated with dronabinol administration in neuro-oncology patients. A secondary aim is to describe the impact that dronabinol has on their quality of life (QOL). Methods: This is an exploratory study of adult patients with WHO Grade III/IV primary gliomas on adjuvant chemotherapy. Power analysis determined a sample size of 34 subjects for 0.80 effect size. Enrollment is ongoing with 18/34 adult patients accrued. Patients take dronabinol 5 mg BID 24 hours prior to, during, and 48 hours after completion of oral/IV chemotherapy. Patients continue their established antiemetic regimen. Between chemotherapy doses, dronabinol is reduced to 2.5 mg daily. Intolerance of dronabinol is defined as 2 or more Grade 3 or greater non-hematologic TOX according to the CTC v.3 definition handbook. Modified Functional Living Index-Emesis (FLIE), Functional Assessment of Cancer Therapy-Brain Tumor (FACT-Br), Mini Mental Status Exam (MMSE), and CINV visual analog scales are collected at specific points for 2 cycles for TOX and QOL data. Results: Subjects are predominately male (n=10); mean age of 45.2 years. Four withdrew due to Grade 3 neurologic TOX of cognitive changes (n=3) despite decreasing dosages; Grade 3 persistent CINV (n=1) despite increasing dronabinol dosage. Increased dosages were required in 4 subjects to better manage CINV. Two required decreased doses for Grade 2 neurologic TOX. Most subjects (n=14) reported stable or improved QOL by FACT-Br and FLIE while the 4 withdrawn subjects reported worsening QOL related to TOX. Conclusions: Dronabinol is safe and effective for administration as an adjunct to standard antiemetic therapy during treatment for primary glioma. The dose may be titrated with minimal toxicities and improvement in QOL. No significant financial relationships to disclose.

Preliminary results of an open-label study to evaluate the efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with carboplatin-containing chemotherapy regimen in patients with ovarian cancer

19652 Background: The use of aprepitant has been shown to offer an advantage in preventing acute and delayed chemotherapy- induced nausea and vomiting (CINV). This study integrates palonosetron and dexamethasone into the regimen to determine the efficacy and safety of this combination. Methods: 50 patients (pts) have enrolled; data has been submitted for 43. Main inclusion criteria were: diagnosis of ovarian (OV), primary peritoneal (PP), fallopian tube (FT) carcinoma Stage I-IV, or papillary serous cancer of the uterus (UPSC); naive to emetogenic chemotherapy Hesketh ≥Level 4, is scheduled to receive paclitaxel 175 mg/m2 IV and carboplatin AUC=6 IV; is able to read and understand the Functional Living Index - Emesis (FLIE) questionnaire. Results: Median age was 61 years, 60% ECOG=0, 86% prior surgery; 68% OV, 14% PP cancers, 7% UPSC, and 5% FT. Metastases were noted in 30% of pts, 21% had visceral metastasis. To date, 70% of patients (32/46) have reported no vomiting, or use of rescue medications during the study and are deemed as complete responders. Based on the 35 pts for whom complete patient diaries have been submitted thus far, the complete response rate is 91% (32/25), compared to 50% (aprepitant alone [The MEC Trial]). No Grade 3–4 treatment related adverse events were reported; Grade 1–2 toxicities included neutropenia (10.5%); anemia, constipation, and nausea (7.9%, each), and fatigue, dyspepsia, and arthralgia (5.3%, each). Some of the toxicities may be related to the chemotherapy, and are not treatment-related to the aprepitant, palonsetron, or dexamethasone. Conclusions: The addition of aprepitant to palonsetron and dexamethasone appears to be very well tolerated. This combination is effective in the prevention of chemotherapy-induced nausea and vomiting when used with emetogenic therapy such as paclitaxel and carboplatin. This research was supported, in part, from a research grant from Merck & Co., Inc. Whitehouse Station, NJ. No significant financial relationships to disclose.

Prevention of chemotherapy-induced delayed nausea and vomiting with aprepitant in patients recieving highly emetogenic-five day cisplatin regimens

14125 Background: It has been shown that addition of the NK1 receptor antagonist aprepitant to 5HT3 antagonist plus dexamethasone is more effective than just the 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis due to high dose cisplatin and also that this effect lasts for multiple cycles. This study evaluated whether the antiemetic efficacy of aprepitant could be sustained for 5 day cisplatin regimens. Methods: Patients receiving cisplatin 20mg/m2/day for 5 days (PEB and TCF regimens ) were randomized to one of the following two regimens: (1) aprepitant 125 mg 1 hour before cisplatin on day 1 and aprepitant 80 mg on days 2 and 3 (n = 17); (2) placebo before cisplatin on days 2 to 7 (n = 19). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 7. The primary end point was complete response (no emesis and no rescue therapy) over 7 days following cisplatin in up to six cycles analyzed by a modified intent-to-treat approach. Secondary end point was evaluated using Functional Living Index-Emesis questionnaire. Treatment comparisons were made using logistic regression models and P value calculated using the chi square test due to small sample size. Results: In the acute period, 83% and 56% of patients were without emesis in groups I and II, respectively (P < .01 for group I v group II). In the delayed period upto day 5, the proportion of patients without emesis in groups I and II, was 59% and 32%, respectively (P < .01 for groups I v group II). In the extended period day 6 and 7 the proportion of patients without emesis in groups I and II was 50% and 38% respectively (P< .01 for groups I v II). The distribution of nausea scores in the delayed period beyond day 5 was lower when comparing group I with group II (P < .05 for days 6 and 7). Two serious adverse events of diarrhea were probably attributed to aprepitant. Conclusions: Once daily oral administration of aprepitant was effective and superior in reducing delayed emesis and nausea after 5 days cisplatinum regimen when added to 5HT3 antagonist plus dexamethasone. This benefit persists upto day 7. Confirming and extending previous results aprepitant should be used in triple combination in patients receiving 5 day cisplatin regimens. No significant financial relationships to disclose.

Chemotherapy-induced nausea and vomiting—incidence and impact on patient quality of life at community oncology settings

The present study sought to determine the prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) across ten community oncology settings. The effect of CINV on quality of life (QOL) was also evaluated. Cancer patients who were scheduled for their first cycle of a new chemotherapy regimen were recruited from ten community oncology clinics. Study participants recorded occurrence of CINV by completing a daily diary each day for the first 8 days after treatment during each cycle and the Functional Living Index-Emesis (FLIE) before chemotherapy, at the end of day 1 and day 6 after chemotherapy. Mixed model regression analysis was used to explore the association between occurrence of CINV at cycle 1 and subsequent cycles and its impact on patient QOL. One hundred and fifty-one patients provided information for at least one cycle. During cycle 1, only 33% had neither acute nor delayed CINV. Of the 36% patients who developed acute CINV, 8% developed acute CINV only. Of the 59% who developed delayed CINV, 53% reported delayed only and 47% reported acute and delayed CINV. A similar pattern was seen at cycles 2 and 3. Experience of CINV at cycle 1 was associated with the development of CINV at cycles 2 and 3. Occurrence of CINV significantly interfered with patient QOL as assessed by the FLIE. CINV remained a substantial problem for patients receiving chemotherapy in this community-based sample, especially delayed CINV. CINV significantly interfered with patient QOL and daily functioning.

Delayed Nausea and Vomiting Continue to Reduce Patients' Quality of Life After Highly and Moderately Emetogenic Chemotherapy Despite Antiemetic Treatment

Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. We compared the impact of acute (during the first 24 hours postchemotherapy) and delayed (days 2 through 5 postchemotherapy) CINV on patients' quality of life (QoL) after highly or moderately emetogenic chemotherapy (HEC and MEC, respectively). This prospective, multicenter, multinational study was conducted in 14 medical practices on cancer patients undergoing either HEC or MEC treatment. Patients recorded episodes of nausea and vomiting in a diary. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire at baseline and on day 6. A total of 298 patients were assessable (67 HEC patients, 231 MEC patients). Emesis was reported by 36.4% of patients (13.2% acute, 32.5% delayed) and nausea by 59.7% (36.2% acute, 54.3% delayed). HEC patients reported significantly lower mean FLIE total score than MEC patients (95.5 v 107.8 respectively; P = .0049). Among all patients, the nausea score was significantly lower than the vomiting score (50.0 and 55.3, respectively; P = .0097). Of the 173 patients who experienced neither vomiting nor nausea during the first 24 hours postchemotherapy, 22.9% reported an impact of CINV on daily life caused by delayed CINV. CINV continues to adversely affect patients' QoL despite antiemetic therapy even after treatment with only moderately emetogenic chemotherapy regimens, and even in the subgroup of patients who do not experience nausea and vomiting during the first 24 hours. On the basis of the FLIE results in this study, nausea had a stronger negative impact on patients' daily lives than vomiting.

The impact of chemotherapy-induced nausea and vomiting on health-related quality of life

The objectives of this prospective observational study were to estimate the frequency of patients who reported an impact of chemotherapy-induced nausea and vomiting (CINV) on their daily life and to evaluate the determinants of such an impact. Adult cancer patients at seven Italian oncology centers who were receiving cisplatin-containing regimens reported incidence and intensity of CINV for eight consecutive days in a diary and completed a Functional Living Index for Emesis (FLIE) questionnaire. Overall, 34% of patients reported vomiting and 62% reported nausea after chemotherapy. On days 1 to 5 after receiving chemotherapy, 67% of patients who had at least one emetic episode and 77% of those who suffered from at least mild nausea experienced an impact on their daily activities as measured on the FLIE questionnaire. More than 90% of all patients with both acute and delayed nausea or vomiting reported an impact on their daily life. Both acute and delayed vomiting contributed in similar measure to impact daily life; however, the importance of delayed nausea was greater than that of acute nausea. Despite antiemetic prophylaxis, CINV is still prevalent and often impacts the daily life of patients in Italy, especially in the delayed phase. The duration more than the severity seems to be responsible for the impact of CINV on the patients' daily lives.

Outcomes and health status of patients undergoing usual care for highly emetogenic chemotherapy

18591 Background: Chemotherapy-induced nausea and vomiting (CINV) remains a significant issue for patients, especially management of delayed symptoms. The Perugia 2004 antiemetic guidelines recommended that anthracycline/cyclophosphamide (A/C) combination regimens be considered as high risk emetogenic potential. The aim of our study was to determine the extent of CINV, and effect on quality of life for chemotherapy-naïve patients in a practice-based environment. Methods: Eligible patients were receiving their 1st cycle of high risk emetogenic or carboplatin chemotherapy, administered with “standard care” (5HT3 antagonist + dexamethasone) antiemetics (use of NK1 antagonists excluded). Patients completed a daily diary for 5 days post chemotherapy, capturing data on CINV activity and rescue medications usage. Emesis and nausea-specific health status was measured by the Functional Living Index - Emesis (FLIE); general health status was assessed using a 100mm VAS (EQVAS). Results: Of 74 patients, 42 received an A/C regimen, 16 cisplatin and 16 carboplatin. Overall complete response (no vomiting, no use of rescue antiemetics during the study period) was 60% in patients receiving carboplatin, 24% A/C and 21% cisplatin. During the delayed phase, mean total emesis episodes for carboplatin was 0.6, A/C 2.21 and cisplatin 4.08. Patients receiving carboplatin reported less delayed nausea, and better outcomes for FLIE and EQVAS scores. Treatment with either A/C or cisplatin was associated with similar deterioration in nausea control across the study period, and similar impact on FLIE scores (see table ). Conclusions: Our results are consistent with the recommendation that A/C regimens be considered highly emetogenic, with similar impact on patient symptoms and quality of life compared with cisplatin. Delayed CINV remains a target for antiemetic intervention. Similar studies need to be repeated in patients receiving additional NK1 antagonists to assess their impact on CINV outside clinical trials. [Table: see text] [Table: see text]

Ondansetron (O) with or without dexamethasone (D) for the prevention of chemotherapy (C)-induced nausea and vomiting (CINV)

18558 Background: Adition of D to the standard antiemetic treatment for CINV prevention is frequent, despite the lack of benefit evidence in controlled clinical trials. In this study we compare the impact of O treatment with or without D on daily life, in patients (pts) under treatment with high or moderately emetogenic C. Methods: Longitudinal, randomized and prospective study. All pts who received anticancer treatment with high or moderately emetogenic C were included, and randomly assigned to group A (O 8 mg iv and D 8 mg iv) or group B (O 8 mg iv). Evaluable pts did not have to receive any medication which could modify the antiemetic effect of treatment within the 24 hours following the administration of CH and had to be able to answer an autoadministered questionnaire. After 24 hours, the Functional Living Index- Emesis (FLIE), a daily life index which consists of 18 questions divided into two domains: nausea and vomiting, had to be completed. Data were analyzed by independent mean sample t-test, and ANOVA One-Way, with a 0.05 significance level. Results: Between December/04 and November/05 233 patients (age average: 59.24; range 21–87) were randomly assigned to antiemetic treatment with (n = 125) or without D (n = 108). Both groups were well balanced as regards the type of chemotherapy, sex and age, and all patients were evaluable. No significant effects were observed between both groups when the global data were analyzed. However, when the sample was stratified by type of chemotherapy, a significantly lower impairment (55.1 vs 51.3; p < .05) was detected in the nausea domain in those patients who received moderately emetogenic chemotherapy. Conclusion: In our sample of patients we observed benefits in the impact on daily life, by the addition of D to the O as preventive treatment of CINV, in those patients that received moderately emetogenic chemotherapy. No significant financial relationships to disclose.

Comparison of the efficacy and safety of combinations of metopimazine or ondansetron with methylprednisolone in the prevention of delayed emesis in patients receiving chemotherapy

ABSTRACTBackground: Delayed emesis following chemotherapy in cancer patients remains an important challenge for treatment and contributes to poor quality of life and treatment compliance.Objectives: To compare the efficacy and tolerability of associations of metopimazine and ondansetron with methylprednisolone for the prevention of delayed chemotherapy-induced nausea and emesis.Methods: A randomised, open-label, observational, cross-over design was used to compare two treatment strategies following two consecutive sessions of chemotherapy separated by at least 1 week. Patients were randomised to treatment with sublingual metopimazine (15 mg tid) or ondansetron lyophilisate (8 mg bid) for 5 days. All patients received oral methylprednisolone (48 mg). Patients reported episodes of nausea and emesis in a diary, and completed the Functional Living Index Emesis quality of life questionnaire. Adverse events were also evaluated.Results: Ninety-nine patients were included in the study, 79.5% of whom were women, with a mean age of 52.7 years. Breast cancer was the most common individual cancer and most patients were receiving combinations of cytotoxic drugs. Treatment was successful at preventing delayed emesis in 73.6% of patients during treatment with the metopimazine–methylprednisolone association and 57.5% during the ondansetron–methylprednisolone association. Analysis of discordant pairs revealed a significant benefit in favour of the metopimazine–methylprednisolone association ( p = 0.006). No significant difference was observed between treatments for the overall quality of life score. The incidence of gastrointestinal disorders, particularly constipation, was significantly higher during ondansetron–methylprednisolone treatment ( p = 0.0112).Conclusion: Metopimazine is an effective and well-tolerated alternative to setrons for the treatment of delayed nausea and emesis in patients undergoing chemotherapy.

The oral NK 1 antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials

In this work, data from two phase III studies were pooled to further evaluate the NK 1 antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (⩾70 mg/m 2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2–4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2–3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.

Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting After Moderately High to Highly Emetogenic Chemotherapy

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.

Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer After Moderately Emetogenic Chemotherapy

This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy. Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire. Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated. The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.

Chemotherapy-Induced Emesis: Quality of Life and Economic Impact in the Context of Current Practice in Canada

In this study, we estimated the proportion of patients who experience chemotherapy-induced nausea and vomiting (CINV) in current practice and evaluated the impact of CINV on quality of life and cost in Canada. Patients receiving highly emetogenic chemotherapy were recruited from 4 Canadian oncology centers. Patients used diaries to record information on their activities, incidence of nausea and vomiting, and health resources consumed each day for 5 days following chemotherapy. They also completed the Functional Living Index–Emesis (FLIE) questionnaire and a health utility instrument before chemotherapy and 5 days later. Of the 323 patients recruited, 266 (82%) completed their diary. On day 1, 26% of patients reported nausea or vomiting (acute emesis). From day 2 to day 5 after chemotherapy, 44% reported nausea or vomiting (delayed emesis). Patients who experienced nausea or vomiting during the study period had a decrease in FLIE score of 22% and a decrease in health utility of 15%. Patients with nausea or vomiting reported an average of 19 hours per cycle during which they were unable to perform their normal activities. Also, friends or relatives spent an average of 10 hours helping these patients. Incremental medical costs per patient experiencing CINV were $61 Canadian. Including productivity losses, total incremental costs were $592 Canadian per patient. Despite use of antiemetics, CINV remains problematic, impacting the quality of life of patients with cancer and increasing costs.

Chemotherapy-induced nausea and vomiting in routine practice: a European perspective.

The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

The economic burden of chemotherapy-induced nausea and vomiting and its impact on the quality of life of Italian cancer patients

6071 Background: In Italy, the economic burden of chemotherapy-induced nausea and vomiting (CINV) and its impact on a patient's daily life have received little attention. Methods: Prospective observational study in 7 oncology centers. Cancer patients receiving cisplatin-containing regimens reported the incidence and intensity of CINV for 8 consecutive days in a diary and completed a Functional Living Index for Emesis (FLIE) questionnaire. Costs related to emesis (direct medical and non-medical costs and indirect costs, including adverse events) and costs of antiemetic therapy were recorded from the perspectives of the hospital, the patient, and the National Health Service (NHS). Costs from the patient's perspective were obtained using a validated questionnaire. The endpoint “No or minimum Impact on Daily Life” (NIDL) is defined as a total score of 108 FLIE points (average item score >6 on a 7-point scale). Results: 62 of 169 enrolled patients (36.7%) had at least one emetic episode and 102/169 (60.4%) experienced mild nausea. Mean costs per patient of acute and delayed emesis are shown in the table. The impact of CINV on a patient's ability to carry out daily activities was evaluated in 155 patients. Impact on patients' daily life occurred because of nausea (77/155; 49.7%) and vomiting (64/155, 41.3%). Conclusions: 60% of cisplatin-treated patients suffered from nausea and 33% from vomiting. CINV affected patients' daily life in more than 40% of the cases. Costs for prophylaxis and management of emesis are high and variable. The economic burden of CINV and its impact on patients' daily life (especially in the delayed phase) is still considerable despite current antiemetic prophylaxis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc. Ballatori Partnership, LLC, Merck & Co., Inc.

The economic burden of chemotherapy-induced nausea and vomiting and its impact on the quality of life of Italian cancer patients

6071 Background: In Italy, the economic burden of chemotherapy-induced nausea and vomiting (CINV) and its impact on a patient's daily life have received little attention. Methods: Prospective observational study in 7 oncology centers. Cancer patients receiving cisplatin-containing regimens reported the incidence and intensity of CINV for 8 consecutive days in a diary and completed a Functional Living Index for Emesis (FLIE) questionnaire. Costs related to emesis (direct medical and non-medical costs and indirect costs, including adverse events) and costs of antiemetic therapy were recorded from the perspectives of the hospital, the patient, and the National Health Service (NHS). Costs from the patient's perspective were obtained using a validated questionnaire. The endpoint “No or minimum Impact on Daily Life” (NIDL) is defined as a total score of 108 FLIE points (average item score >6 on a 7-point scale). Results: 62 of 169 enrolled patients (36.7%) had at least one emetic episode and 102/169 (60.4%) experienced mild nausea. Mean costs per patient of acute and delayed emesis are shown in the table. The impact of CINV on a patient's ability to carry out daily activities was evaluated in 155 patients. Impact on patients' daily life occurred because of nausea (77/155; 49.7%) and vomiting (64/155, 41.3%). Conclusions: 60% of cisplatin-treated patients suffered from nausea and 33% from vomiting. CINV affected patients' daily life in more than 40% of the cases. Costs for prophylaxis and management of emesis are high and variable. The economic burden of CINV and its impact on patients' daily life (especially in the delayed phase) is still considerable despite current antiemetic prophylaxis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc. Ballatori Partnership, LLC, Merck & Co., Inc.