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Purpose: We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC).Methods: Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life.Results: Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups.Conclusions: Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR. [ABSTRACT FROM AUTHOR]

Purpose: Neurokinin-1 receptor antagonist (NK1RA) is recommended to prevent chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly or moderately emetogenic chemotherapy (HEC or MEC, respectively). We previously reported that aprepitant, an NK1RA, was needed to control CINV in 43% and 12% of patients who received HEC and MEC, respectively (Support Care Cancer 23:905–912, 2015). To elucidate the cost-effectiveness of aprepitant in these patients, a cost-utility analysis according to the necessity of aprepitant was performed. Methods: A decision-analytic model was developed according to the necessity of aprepitant and CINV responses in both acute and delayed phases of chemotherapy. Probabilities of health states and medical costs were derived from the results of the abovementioned trial. Result: In patients who received HEC and needed aprepitant, the incremental cost-effectiveness ratio (ICER) with aprepitant, relative to the regimen with no aprepitant, was 7912 US dollars (USD) per quality-adjusted life year (QALY) gained, which was far below the commonly accepted threshold of 50,000 USD/QALY. The ICER was 27,457 USD/QALY in patients who received MEC and needed aprepitant. In contrast, in patients who received HEC or MEC but did not need aprepitant, the ICER was 175,959 or 478,844 USD/QALY, respectively. Conclusion: Regardless of whether a patient received HEC or MEC, aprepitant use was highly cost-effective for patients who truly needed it. These results warrant further research to predict the necessity of NK1RA treatment before initiating emetogenic chemotherapies. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced nausea and vomiting (CINV) remain significant clinical problems, especially in the delayed phase (24-120 h after chemotherapy). Amisulpride is a dopamine D2/D3-receptor antagonist previously shown to be an effective intravenous antiemetic. We conducted a randomised, double-blind study to characterise the dose response of oral amisulpride in delayed phase CINV.Methods: Chemotherapy-naïve patients receiving cisplatin ≥ 70 mg/m2 or an anthracycline-cyclophosphamide regimen for breast cancer received, on day 1, 20 mg amisulpride and 8-16 mg ondansetron intravenously followed, once daily on days 2-4, by 10, 20 or 40 mg oral amisulpride or placebo. A control group receiving standard three-drug prophylaxis was enrolled for assay sensitivity purposes. The primary endpoint was complete response (CR), defined as no emesis or rescue medication use, in the delayed phase.Results: Three hundred eighteen subjects were evaluable per protocol. CR rate (24-120 h) was 20% with placebo and 46% with 10 mg amisulpride (p = 0.006 after multiplicity adjustment); in the three-drug control group, it was 59%. Emesis, nausea and 0-120-h CR rate were significantly improved with 10 mg amisulpride compared to placebo. Higher doses of amisulpride were not more effective than 10 mg. In patients with acute phase CR, delayed phase CR rate was 44% for placebo, 75% for 10 mg amisulpride (p = 0.022) and 70% for the 3-drug control. No significant differences were seen between groups in safety parameters.Conclusions: Amisulpride 10 mg orally is safe and superior to placebo at preventing delayed CINV caused by highly emetogenic chemotherapy.Trial Registration: NCT01857232. [ABSTRACT FROM AUTHOR]

Despite the widespread use of 5-HT3 antagonists as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) receiving induction chemotherapy, nausea and vomiting persist in many cases. We performed a Phase II single-arm study evaluating the use of aprepitant on days 1-5, in combination with a 5-HT antagonist on days 1-3, in AML patients undergoing induction chemotherapy with daunorubicin on days 1-3 plus cytarabine, given as a continuous infusion, on days 1-7. This was compared to a retrospective cohort of AML patients that received the same chemotherapy regimen with a 5-HT antagonist but without aprepitant. The cumulative incidence of vomiting/retching by the end of day 5 was significantly lower in the aprepitant vs. the control group (26.3 vs. 52.8%, p = 0.013). The cumulative incidence of nausea by the end of day 5 was 61% in the aprepitant group vs. 75% in the control group. The total use of supplemental anti-emetics on days 2-5 was also significantly lower in the aprepitant group (p = 0.01). In contrast, the cumulative incidence of vomiting/retching by the end of day 8, the incidence of vomiting/retching on days 6-8, and the use of anti-emetics on days 6-8, were not significantly different between the two groups. The results suggest that the use of aprepitant may be associated with a lower rate of emesis during aprepitant dosing days, but not afterward. However, this requires confirmation in a randomized trial. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with a variety of early- and end-stage malignancies. In light of recent changes in the optimal management of CINV, we undertook this narrative review to compare the latest guidelines published by ASCO (2017), NCCN (2018), and MASCC/ESMO (2016). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, and MASCC/ESMO guidelines for the treatment and prevention of CINV share many fundamental similarities, literature surrounding low and minimal emetic risk regimens is lacking. Data regarding the use of complementary alternative medicine for CINV is particularly scarce and in need of further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event with cancer chemotherapy, despite the availability of effective antiemetic agents. This is a prospective observational study of Italian breast cancer patients treated with anthracycline plus cyclophosphamide (AC), assessed CINV incidence, adherence to national antiemetic guidelines (AIOM 2012), and the relationship with CINV outcomes.Methods: Patients with breast cancer scheduled to receive their first cycle of an AC-based regimen were enrolled at 12 Italian centers and their clinical data prospectively recorded. CINV incidence was assessed from patient diaries after the first chemotherapy cycle. The relationship between guideline adherence and CINV outcomes was examined using multiple logistic regression.Results: The overall incidence rates of nausea and vomiting among 246 evaluable patients were 63.0 and 25.4%, respectively. Most patients received a 5-HT3-RA agent and dexamethasone for acute phase CINV prophylaxis, whereas a triple combination including aprepitant (NK1-RA), consistent with national guidelines, was used in only 45.5% of cases. In the delayed phase, the guideline adherence was 48.8%, while the overall adherence was 43.5%. After adjusting for confounding factors, adherence to antiemetic prophylaxis guidelines was associated with a significant reduction in the odds of three endpoints, namely any nausea, "significant nausea," and vomiting (OR = 0.49, OR = 0.54, and OR = 0.48, respectively), and a 90% increase in the odds of overall complete protection (OR = 1.90).Conclusions: CINV is still a critical issue in AC-treated patients, despite antiemetic treatment. Non-adherence to antiemetic guidelines may lead to poorer outcomes and indicates the need for strategies to enhance the use of guidelines in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancer patients still suffer from CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response.Methods: This study included a subset of patients previously enrolled in a randomised controlled trial; 156 patients were evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study's efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR0-24) and delayed (CR24-120) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for the CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables.Results: Multivariate logistic regression analysis revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval [CI] 1.74-72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14-11.58; p = 0.029) were significant predictors of CR0-24. No significant association of CR24-120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis.Conclusions: ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy.Trial Registration: Clinical trial information: UMIN 000009335. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients.Methods: This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase.Results: Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated.Conclusion: A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines.Trial Registration: ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 ). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine the efficacy of ginger for reducing chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients receiving adriamycin and cyclophosphamide (AC) regimens.Methods: We enrolled breast cancer patients receiving AC who experienced moderate to severe nausea or vomiting during the first chemotherapy cycle. Subjects were randomized to receive a 500-mg ginger capsule or placebo twice a day for 5 days starting on the first day of the second AC cycle and were switched to the other treatment in the third cycle. All participants also received ondansetron and dexamethasone for CINV prophylaxis. Nausea severity was recorded once a day during the first 5 days of each cycle. The primary outcome was reduction in nausea score.Results: Thirty-four subjects (68 cycles of AC) were enrolled. Mean (range) maximum nausea score in the first AC cycle was 58 (40-90). Thirty-three subjects (97 %) received the same AC doses in the second as in the third cycle. Mean (±standard error) maximum nausea scores in patients receiving ginger and placebo were 35.36 (±4.43) and 32.17 (±3.71), respectively. The difference in mean maximum nausea scores was 3 (95 % confidence interval, -3 to 9; P = 0.3). There were no significant differences between ginger and placebo in terms of vomiting incidence and severity, rescue medication use, chemotherapy compliance, and adverse events.Conclusions: Ginger (500 mg) twice daily was safe, but conferred no additional benefit in terms of reducing nausea severity in breast cancer patients receiving AC and ondansetron and dexamethasone for CINV prophylaxis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to test a new blood-based assay for its ability to predict delayed chemotherapy-induced nausea.Methods: Blood drawn from consented patients prior to receiving their first platinum-based therapy was tested for glutathione recycling capacity and normalized to total red cell numbers. This number was used to predict nausea and then compared to patient reported outcomes using the Rotterdam Symptom Check List and medical records.Results: We show that the pathways involved in the glutathione recycling are stable for at least 48 h and that the test was able to correctly classify the risk of nausea for 89.1 % of the patients. The overall incidence of nausea was 21.9 % while women had an incidence of 29.6 %.Conclusions: This might be the first objective test to predict delayed nausea for cancer patients receiving highly emetogenic chemotherapy. We believe that this assay could better guide clinicians in their efforts to provide optimal patient-oriented care. [ABSTRACT FROM AUTHOR]

Purpose: This review summarizes the recommendations for the prophylaxis of nausea and vomiting in adults receiving highly emetogenic chemotherapy (HEC) which includes cisplatin, mechlorethamine, streptozocin, cyclophosphamide >1500 mg/m2, carmustine, dacarbazine, and the combination of an anthracycline and cyclophosphamide (AC) administered to women with breast cancer, as agreed at the MASCC/ESMO Antiemetic Guidelines Update meeting in Copenhagen in June 2015.Methods: A systematic review of the literature using PubMed and the Cochrane Database from 2009 to June 2015 was performed.Results: The NK1-receptor antagonists netupitant (300 mg given in combination with palonosetron 0.5 mg as NEPA) and rolapitant have both completed phase II and III programs and were approved by FDA (both) and EMA (NEPA) in 2014-2015. Addition of one of these agents (or of (fos)aprepitant) to a combination of a serotonin (5-HT)3-receptor antagonist and dexamethasone improved the number of patients with a complete response (no emesis and no rescue medication) days 1-5 after AC HEC with 8-9 % and after non-AC HEC by 8-20 %. Olanzapine has improved control of delayed nausea as compared to aprepitant in a randomized open designed study. In the prophylaxis of delayed nausea and vomiting, metoclopramide is an option instead of aprepitant in patients receiving cisplatin-based chemotherapy and dexamethasone is an option instead of aprepitant in patients receiving AC chemotherapy.Conclusions: Two new NK1-receptor antagonists (netupitant and rolapitant) have been included in the updated recommendations as additional options to aprepitant or fosaprepitant. Addition of one of these NK1-receptor antagonists to a combination of a 5-HT3-receptor antagonist and dexamethasone is recommended in both non-AC HEC and AC HEC. Olanzapine is included as an option in HEC in particular if nausea is the main symptom. [ABSTRACT FROM AUTHOR]

Purpose: In a comparative phase 3 study involving 1114 Japanese patients receiving highly emetogenic chemotherapy (HEC), palonosetron (PALO) was found to be superior to granisetron (GRA) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in the delayed phase. This post hoc analysis of the phase 3 study evaluated the efficacy of PALO for the control of nausea.Methods: The proportion of patients without nausea was assessed at 24-h intervals during the acute phase (0-24 h), delayed phase (24-120 h), and overall (0-120 h). No nausea rates were also evaluated by sex, type of chemotherapy (cisplatin or doxorubicin/epirubicin plus cyclophosphamide [AC/EC]), and age (<55 vs. ≥55 years). Nausea severity was categorized using a 4-point Likert scale (0 = no nausea to 3 = severe nausea).Results: The proportion of patients without nausea was significantly higher in the PALO arm than in the GRA arm in the delayed phase (37.8 % vs. 27.2 %; p = 0.002) and overall (31.9 % vs. 25.0 %; p = 0.0117). When analyzed by stratification factors, the proportion of patients without nausea was significantly higher in the PALO arm in the delayed phase and overall in patients who were female, younger, or treated with cisplatin and in the delayed phase in patients who were older or treated with doxorubicin or epirubicin plus cyclophosphamide (all p < 0.05).Conclusions: PALO was more effective than GRA in prophylaxis of HEC-induced nausea in the delayed phase and overall. In addition, PALO was more effective than GRA in young and female patients, who are at high risk of CINV, both in the delayed phase and overall. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.Methods: A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT3 RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.Results: Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).Conclusions: This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC. [ABSTRACT FROM AUTHOR]

Purpose: Dexamethasone, plus a 5-HT3 receptor antagonist and an NK-1 receptor antagonist are recommended for controlling the chemotherapy-induced nausea and vomiting (CINV) of highly emetogenic chemotherapy. Several days of dexamethasone are effective for CINV; however, dexamethasone also has side effects. The purpose of this trial was to investigate whether the use of a second-generation 5-HT3 receptor antagonist and an NK-1 receptor antagonist could allow a reduced dose of dexamethasone for breast cancer patients receiving highly emetogenic chemotherapy.Methods: Eighty breast cancer patients who received an anthracycline-cyclophosphamide combination regimen were enrolled. The patients were randomized to arm A (dexamethasone days 1-3) and arm B (dexamethasone day 1). The primary endpoint was complete response (CR) (no emetic episodes and no rescue medication) during the overall phase (days 1-5). The secondary endpoints were the CR during the delayed phase (days 2-5), complete control (CC) (no emetic episodes, no rescue medication, and no more than mild nausea) during the overall phase, and the safety of this antiemetic therapy.Results: There were no significant differences in the rates of CR and CC between arm A and B as follows: CR overall phase--arm A: 82.9%, 90% confidence interval [CI] 71.3-90.5% vs arm B: 82.1%, 90% CI 70.0-90.0%; p = 1.00; CR delayed phase--arm A: 87.8%, 90% CI 77.0-93.9% vs arm B: 94.9%, 90% CI 85.6-98.3%; p = 0.43; CC overall phase--arm A: 48.8%, 90% CI 36.4-61.3% vs arm B: 61.5%, 90% CI 48.4-73.2%; p = 0.27. There were very few adverse events and no severe adverse events associated with this antiemetic therapy.Conclusions: The results suggest that the antiemetic effect provided by dexamethasone administered for 3 days can be obtained by dexamethasone administered for 1 day. [ABSTRACT FROM AUTHOR]

Purpose: Rolapitant is a novel, long-acting neurokinin-1 (NK-1) receptor antagonist. This study evaluated the safety and efficacy of four different doses of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC).Methods: This randomized, double-blind, active-controlled, global study was conducted in patients receiving cisplatin-based chemotherapy ≥70 mg/m(2). Patients received a 9, 22.5, 90, or 180 mg oral dose of rolapitant or placebo with ondansetron and dexamethasone on day 1 of chemotherapy. The primary end point was complete response (CR; no emesis and no use of rescue medication) in the overall (0 to 120 h) phase of cycle 1. Other assessments were CR in delayed (24-120 h) and acute (0-24 h) phases, no emesis, no significant nausea, and no nausea.Results: Four hundred fifty-four patients were randomized. All doses of rolapitant improved CR with the greatest benefit observed with rolapitant 180 mg vs. active control in the overall phase (62.5 and 46.7 %, p = 0.032) and in the acute (87.6 vs. 66.7 %, p = 0.001) and delayed (63.6 vs. 48.9 %, p = 0.045) phases. Rates for no emesis and no significant nausea were significantly (p < 0.05) higher with rolapitant 180 mg vs. active control in the overall, acute, and delayed phases. Treatment-related adverse events were largely considered related to the chemotherapy and included constipation, headache, fatigue, and dizziness which were mostly mild or moderate and were similar across treatment groups.Conclusion: All doses of rolapitant were well tolerated and showed greater CR rates than active control. Rolapitant 180 mg demonstrated significant clinical efficacy for preventing CINV in the overall, delayed, and acute phases for patients receiving HEC. [ABSTRACT FROM AUTHOR]

Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥50 mg/m). Methods: Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy). Results: Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each). Conclusions: Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV. [ABSTRACT FROM AUTHOR]

Purpose: Individualized patient care may help reduce the incidence of adverse drug events in systemic cancer therapy. This study was conducted to explore the feasibility and potential of additional pharmaceutical care for breast and ovarian cancer patients. Methods: The study was designed as a prospective, multicentered cohort study with a control group. Ninety-eight breast or ovarian cancer patients were recruited from outpatient oncology clinics and primary care oncologists: initially into the control group receiving standard care and after implementation of pharmaceutical care into the intervention group consisting of additional patient counseling on the management of treatment-associated adverse events and optimization of supportive medication. Primary outcome was the complete response to the antiemetic prophylaxis. Secondary endpoints were the severity of nausea, frequency of emesis, health-related quality of life, and patient satisfaction with information on cancer treatment education. Results: Forty-eight patients were included in the control group and 50 in the intervention group. Of the patients, 35.4% in the control group and 76.0% in the intervention group ( p < 0.001) had a complete response to the antiemetic prophylaxis. The severity of acute and delayed nausea was not reduced. The global health scale and two symptom scales (nausea and vomiting, appetite loss) of the EORTC QLQ-C30 questionnaire were positively affected by pharmaceutical care. Patient satisfaction with information was significantly higher in the intervention group. Conclusions: Patients with breast and ovarian cancer seem to benefit from pharmaceutical care, as suggested by improved patient-reported outcomes such as emetic episodes, quality of life, and patient satisfaction after implementation. [ABSTRACT FROM AUTHOR]

This is a phase II trial evaluating efficacy and safety of aprepitant (AP) in combination with 5-HT3 antagonist and adjusted dose dexamethasone in patients receiving high-dose cyclophosphamide (CY) and filgrastim for stem cell mobilization. We used Simon's optimal two-stage design constrained to fewer than 40 patients with 10% type I error and 85% statistical power. The first stage of the study required accrual of 18 response-evaluable patients. The primary endpoint was the control of vomiting without the use of any rescue anti-emetics at 24 h after the administration of high dose CY (4 g/m). If emesis was controlled in ≥9 patients, an additional cohort of 17 patients would be enrolled. The null hypothesis would be rejected if there were ≥20 responses among 35 patients. Forty patients were enrolled, five of whom were not evaluable for response. Eighteen evaluable patients were enrolled in the first stage. Acute emesis was controlled in 10 patients; therefore, enrollment proceeded to stage 2. An additional 17 patients were enrolled; 20/35 response-evaluable patients (57%) did not develop acute vomiting or require rescue anti-emetics, thus achieving the goal of the study. A total of 22/35 response-evaluable patients (63%) met the secondary endpoint of delayed emesis control (days 2-5). Thirty-three out of 35 patients underwent successful stem cell mobilization. No ≥ grade 3 AP-related adverse events were noted. The AP regimen can effectively control acute and delayed emesis in the majority patients receiving high-dose CY. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. Methods: Eighty chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy, were enrolled in this randomised, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day 1 and oral dexamethasone 4 mg twice a day on days 2 and 3. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: 5 and 4 days before chemotherapy once daily, 3 and 2 days before chemotherapy twice daily, 1 day before to 5 days after chemotherapy thrice daily. The primary endpoint was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24-120 h after chemotherapy). Results: The proportion of patients achieving complete response improved from 40% to 62.5%, ( p = 0.04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89.3 × 60.7%, p = 0.01). Adverse events did not significantly differ between study arms. Conclusions: Gabapentin is a low-cost strategy to improve complete control of CINV, specially delayed CINV control. [ABSTRACT FROM AUTHOR]

Purpose: Physicians and nurses often underestimate the incidence of chemotherapy-induced nausea and vomiting (CINV) after both highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This study assesses physicians' and nurses' perceptions of CINV in their own practices after the introduction of aprepitant.Methods: A prospective observational study of patients receiving the first cycle of HEC regimens with CDDP and without CDDP or MEC was performed. Eligible patients completed a 6-day diary recording emetic episodes, nausea assessment, and antiemetic medication use. Physicians and nurses estimated the incidence of acute and delayed CINV after the first administration of HEC and MEC. The observed incidence rates of CINV were compared with the rates predicted by healthcare providers. Aprepitant was given to patients receiving HEC regimes with CDDP.Results: Twenty-nine physicians and nurses and 95 patients (87% receiving HEC and 14% MEC) were recruited. The global control of CINV was 66.67% for all patients and 73.33%, 47.06%, and 55.56% for patients receiving HEC regimens with CDDP, HEC regimens without CDDP and MEC, respectively. Physicians and nurses underestimated the control of acute CINV in patients receiving HEC regimens with CDDP, but they accurately predicted the control of delayed CINV. All physicians and nurses predicted the control of acute CINV after HEC regiments without CDDP and after MEC quite accurately, whereas they overestimated the control of delayed CINV after both regimens.Conclusions: Aprepitant allows for better control of CINV in HEC regimens with CDDP, and this control is accurately perceived by physicians and nurses. However, physicians and nurses overestimate the control of delayed CINV after HEC regimens without CDDP and after MEC. CINV is still an important target for improved therapeutic intervention and the healthcare providers must be aware of its actual incidence. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based highly emetogenic chemotherapy (HEC) displays a biphasic pattern of emesis with both an early and delayed period. In contrast, moderately emetogenic chemotherapy (MEC) has a monophasic pattern. The objective of this analysis was to further investigate the impact of the NK1-receptor antagonist aprepitant on these patterns.Methods: Three phase III HEC (patients scheduled to receive cisplatin-based chemotherapy) and one phase III MEC (breast cancer patients scheduled to receive anthracycline plus cyclophosphamide (AC)) trials of aprepitant were included. In all studies, patients were randomized in a 1:1 ratio to an aprepitant regimen (aprepitant plus ondansetron plus dexamethasone) or the standard regimen (ondansetron plus dexamethasone). The exact dosing regimen for ondansetron and dexamethasone was different in each study. In a post hoc analysis, multivariate logistic regression models were used to assess the impact on first emesis at different time intervals after chemotherapy.Results: One thousand five hundred twenty-seven patients and 856 patients were randomized and assessed for efficacy in the HEC and MEC trials, respectively. For HEC, aprepitant reduced the risk of first emesis by 38-77% vs. standard regimen, beginning 15-18 h after cisplatin and extending to 60 h. For MEC, aprepitant reduced the risk of first emesis by 38-61% vs. active control, beginning 3 h after AC and for up to 12 h.Conclusions: Time of onset and duration of enhanced control of emesis with the addition of aprepitant differed between HEC and MEC. This suggests that the pattern of NK1-sensitive mechanisms may vary for different chemotherapy regimens. [ABSTRACT FROM AUTHOR]

ntiemetic drug development can follow the same logical path as antineoplastic drug development from appropriate preclinical models through Phase I, Phase II, and Phase III testing. However, due to the marked success of antiemetic therapy over the last 25 years, placebo antiemetic treatment against highly or moderately emetogenic chemotherapy is not acceptable. Promising antiemetic agents therefore rapidly reach Phase III testing, where they are substituted into or added to effective and accepted regimens. One challenge of antiemetic drug development is determining whether substitution is indeed acceptable or whether prior regimens must be maintained intact as a basis for further antiemetic drug development. An additional challenge is the classification of emetogenic level of new antineoplastic agents. Accurate reporting of emetogenicity of such antineoplastic agents in the absence of preventive antiemetic treatment may not be available. However, at the 2009 Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) Consensus Conference, an expert panel used best available data to establish rankings of emetogenicity. Oral chemotherapeutic agents are ranked separately from intravenous agents, recognizing intrinsic differences in emetogenicity as well as differing schedules of administration. Since oral chemotherapeutic agents are often administered in extended regimens, the distinction between acute and delayed emesis is less clear, and cumulative emesis must be considered. As control of vomiting has improved, attention has shifted to control of nausea, a related but distinct and equally important problem. Additional efforts will be necessary to understand mechanisms of nausea and to identify optimal remedies. [ABSTRACT FROM AUTHOR]

Goals Of Work: Certain patient and treatment characteristics are predictive of chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis were: (1) confirm the importance of several previously reported adverse risk factors for CINV in patients receiving chemotherapy, (2) assess the impact of the NK(1) receptor antagonist aprepitant according to these risk factors, and (3) assess the impact of age on antiemetic outcome.Patients and Methods: Patients from two double-blind, placebo-controlled trials were randomized to an active-control group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone 8 mg bid days 2-4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32 mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2-3; dexamethasone 8 mg qd days 2-4). The primary endpoint was complete response (no emesis or rescue therapy use). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact of treatment with aprepitant and previously reported risk factors, using a modified intent-to-treat approach.Main Results: Treatment with aprepitant (p < 0.0001), male gender (p = 0.023), cisplatin dose <80 mg/m(2) (p = 0.001), age >or=65 years (p = 0.021), and five or more alcoholic drinks per week (p = 0.027) were all significantly associated with improved complete response. Aprepitant improved complete response regardless of risk for all factors and neutralized the risk associated with female gender.Conclusions: This analysis confirmed the relevance of several previously reported risk factors for CINV in patients receiving chemotherapy. Aprepitant improved complete response regardless of risk and eliminated the increased risk of CINV associated with the female gender. [ABSTRACT FROM AUTHOR]

Objectives: Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy which may increase morbidity, reduce quality of life and threaten the success of cancer therapy. Aprepitant is effective in preventing CINV, achieving higher complete response (no emesis and no rescue therapy) compared to standard prevention, in patients receiving either highly (HEC) or moderately emetogenic chemotherapy (MEC; absolute reduction = 11 and 13%, respectively). We assessed the cost effectiveness of aprepitant-based vs standard prevention in these indications in Belgium.Materials and Methods: A decision analytical model was developed in MS Excel (Fig. 1). To estimate resource use, two approaches were used. The first is based on the preventive regimens applied in randomized controlled trials comparing aprepitant-based CINV prevention (for HEC: aprepitant days 1-3, ondansetron 32 mg i.v. day 1, oral placebo twice daily days 2-4, oral dexamethasone days 1-4; for MEC: aprepitant days 1-3, ondansetron 16 mg p.o. day 1, placebo on days 2-3, oral dexamethasone day 1), vs a standard regimen (for HEC: oral placebo days 1-3, ondansetron 32 mg i.v. day 1 and 16 mg p.o. days 2-4, oral dexamethasone days 1-4; for MEC: oral placebo, ondansetron 16 mg p.o. days 1-3, dexamethasone day 1) The second analysis is based on current real-world resource use in the Belgian setting in the prevention of CINV using a longitudinal Hospital Database. CINV-specific utility values were used to calculate quality-adjusted life years (QALYs). Drug costs were obtained from official reimbursement listings. Treatment costs for CINV were obtained from a German study and adapted to Belgium.Results: The aprepitant-based regimen is associated with 0.003 and 0.014 more QALYs in HEC and MEC, respectively and with per patient savings of 66.84 (trial based) and 74.62 (real-life based) for HEC and 17.95 (trial based) and 21.70 (real-life based) for MEC. Hence, aprepitant is both more effective and less expensive (=dominant). One-way sensitivity analyses were performed on treatment cost of emesis, the clinical benefit of aprepitant and the cost of ondansetron and showed that the results were robust on the first two parameters but sensitive on the decrease in cost of ondansetron for the moderately emetogenic chemotherapy regimens.Conclusions: In both approaches, the aprepitant-based strategy is more effective and less expensive compared to standard care. [ABSTRACT FROM AUTHOR]

AbstractIntroduction??Posttreatment nausea (PTN) is a common side effect of cytotoxic cancer chemotherapy. Previous retrospective research has suggested that the severity of PTN may be, in part, related to pretreatment psychological factors (e.g., emotional distress and expectations for nausea).Materials and methods??The purpose of the present study was to examine these relationships prospectively, with distress and nausea expectations assessed by validated self-report measures completed in the clinic before the participants? first outpatient treatment infusion and with PTN (0?100) assessed by end-of-day diaries completed at home on each of the first 5?days after treatment. The participants were chemotherapy-naive women (N=56) scheduled for standard adjuvant treatment for stage I?II breast cancer (mean age=45.6?years). PTN was evaluated for acute (days?0?1) and delayed (days?2?5) responses.Results??The results revealed a significant relationship between pretreatment distress and the severity of the patients? subsequent delayed nausea (p<0.007) but not a relationship with acute PTN (p<0.19). No significant relationships were seen between expectations and PTN. However, there was evidence of an additive effect of nausea expectations and distress, with the highest levels of delayed PTN seen in patients with both expectations and higher distress before treatment. The results suggest a selective effect of pre-infusion psychological variables on the delayed phase of nausea after chemotherapy, consistent with an emerging view that the different phases of nausea are mediated by different neural pathways.Conclusion??Future research should examine the possibility that delayed nausea, which the literature suggests is more resistant to antiemetic drugs than acute nausea, might be responsive to psychological interventions before initial treatments. [ABSTRACT FROM AUTHOR]