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Despite the considerable progress achieved in the last 30 years, vomiting and, especially, nausea, continue to be two of the most distressing side-effects of cancer chemotherapy. In the late 1990s, several professional organisations published recommendations on the optimal antiemetic prophylaxis in patients submitted to chemotherapy and/or radiotherapy. The European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) published the results of the third Consensus Conference on antiemetics held in Perugia in June 2009 in Annals of Oncology in 2010 [1]. An update of these recommendations, including studies published from 1 January 2009 to 30 June 2015, was discussed in Copenhagen in June 2015 and is presented in this paper. The methodology for the guideline process is described in detail in the 2010 publication [1]. To change a 2010 recommendation or for a new guideline recommendation to be accepted, a consensus of at least 67% of the expert panellists was needed. As a general rule, the panel considered changes of 10% or greater to be sufficient to warrant the changing of a recommendation. Refereed/Peer-reviewed

Background There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). Patients and methods Patients with a malignant solid tumor who would receive HEC containing 50 mg/m2 or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2–4) and aprepitant (125 mg on day 1 and 80 mg on days 2–3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0–120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). Results Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0–120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0–24 h) period, while at the delayed (24–120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0–120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). Conclusion The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. Clinical Trial Registry Identifier UMIN000004863.

This study was designed to determine the appropriate clinical dose of netupitant (NETU), a new NK1 receptor antagonist (RA), to combine with the 5-HT3 RA, palonosetron (PALO) in a fixed-dose antiemetic combination (NEPA). All NEPA doses provided superior prevention of chemotherapy-induced nausea and vomiting compared with PALO, with NEPA300 (300mg NETU + 0.50 mg PALO) being the best dose studied., Background NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 (5-HT3) RA. This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program. Patients and methods This randomized, double-blind, parallel group study in 694 chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO 0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant (APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm. All patients received oral dexamethasone on days 1–4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0–120 h) phase. Results All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300, respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis, no significant nausea, and complete protection (CR plus no significant nausea) rates during the acute (0–24 h), delayed (25–120 h), and overall phases. Adverse events were comparable across groups with no dose response. The percent of patients developing electrocardiogram changes was also comparable. Conclusions Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with PALO following highly emetogenic chemotherapy; however, NEPA300 was the best dose studied, with an advantage over lower doses for all efficacy endpoints. The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND.

Background Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy. Whether adding a neurokinin-1 receptor antagonist to a first-generation 5HT3 antagonist (1st-5HT3RA) and dexamethasone (DEX) is beneficial in patients on L-OHP-based chemotherapy is controversial. It is unclear whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV. We, therefore, investigated whether PALO+DEX (PALO group) or 1st-5HT3RA+DEX+APR (APR group) was more effective in controlling delayed CINV, as well as risk factors for delayed CINV, in patients with CRC treated with L-OHP-based chemotherapy. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial and compared the incidence of CINV between the PALO and APR groups using propensity score-matched analysis. Risk factors for CINV were identified using logistic regression models. Results Among the 404 eligible patients, those in the PALO group showed a higher incidence of delayed CINV than those in the APR group (nausea: 43.4% vs. 32.4%, P = 0.061; vomiting: 12.5% vs. 4.4%, P = 0.017). The logistic regression analysis identified alcohol consumption, motion sickness, and PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and PALO+DEX regimen as those for delayed vomiting. Conclusions Treatment with the three antiemetics, including APR, was more effective in controlling delayed CINV than prophylactic treatment with the two antiemetics, including PALO. Thus, patients with CRC receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Dexamethasone are often administered to prevent chemotherapy induced nausea and vomiting. The aim of this study was to assess the incidence of, and factors associated with, steroid induced metabolic syndrome in cancer patients receiving high emetic risk chemotherapy with antiemetic dexamethasone therapy. Methods This study was conducted retrospectively chart review of 356 patients who received high emetic risk chemotherapy with dexamethasone, aprepitant, and 5-HT3 antagonist between September 2015 and December 2017 at Chung-Ang University College of Medicine. Fasting plasma glucose levels. systolic blood pressure, diastolic blood pressure, triglyceride, HDL for the diagnosis of metabolic syndrome were performed before chemotherapy and 6 months after the start of chemotherapy. Results In total, 256 patients met the inclusion criteria and were included in analysis. The incidence of newly diagnosis metabolic syndrome was 17.5% (45 patients) after chemotherapy. The incidence of newly diagnosis diabetes and hypertension was 5.8% (15 patients), 26.2% (67 patients) after 6 months follow up. The mean metabolic syndrome score was 1.4 (range: 0-4) after chemotherapy. Multivariate analysis showed significant association of the incidence of streroid induced metabolic syndrome with BMI ≥ 25 (OR = 3.497, 95% CI = 1.064 – 11.494, p = 0.039) and colorectal cancer (OR = 0.088, 95% CI = 0.010-0.731, p = 0.024). Conclusions The incidence of steroid-induced metabolic syndrome after antiemetic dexamethasone therapy was high (17.4%). Therefore, we suggested that carefully measure glucose as well as LDL, triglyceride, blood pressure during antiemetic dexamethasone therapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background The antiemetic standard of care recommended by guidelines for prevention of CINV in patients receiving cisplatin- and AC-based CT is the combination of an NK1 RA, a 5-HT3 RA, and dexamethasone (DEX). An IV formulation of NEPA (fixed combination of the NK1 RA, fosnetupitant and 5-HT3 RA, palonosetron) was recently approved in the US and is under review in Europe. Approval of IV NEPA was based on showing pharmacokinetic bioequivalence of IV fosnetupitant to oral netupitant and similar safety of IV NEPA to oral NEPA in a phase III study in patients receiving cisplatin-based CT. An IV/oral NEPA safety-controlled phase IIIb study was recently completed in patients receiving AC CT. In both studies, there were no injection-site or hypersensitivity reactions associated with IV NEPA. This secondary analysis presents the efficacy of IV NEPA relative to that of oral NEPA and other NK1 RAs in cisplatin and AC settings. Methods Data is compiled from 5 pivotal NEPA studies in a total of 2077 adult chemotherapy-naive patients with solid tumors undergoing either cisplatin- or AC-based CT. IV NEPA was administered as a single 30-min infusion; oral NEPA was given as a single capsule 60 min prior to CT. Patients also received DEX. Data was also reviewed from 9 phase III cisplatin and AC studies with other NK1 RA (aprepitant [APR], fosaprepitant [FOS], rolapitant [ROL]) regimens. No emesis rates are summarized for the overall phase (0-120h) of the initial cycle of CT. No formal statistical comparisons were performed. Results The overall no emesis rates of > 80% for IV NEPA were similar to oral NEPA in both cisplatin and AC settings and were favorable in the context of historical NK1 RA regimens. Table . 1765P Setting/Study IV NEPA + DEX Oral NEPA + DEX APR + 5-HT3RA + DEX FOS + 5-HT3RA + DEX ROL + 5-HT3RA + DEX Cisplatin Schwartzberg 2018 84.2% 88.6% - - Hesketh 2014 - 91.1% - - Zhang 2018 - 75.0% - - Grunberg 2011 - - 74.6% 72.9% Hesketh 2003 - - 77.7% - - Poli-Bigelli 2003 - - 66% - - Schmoll 2006 - - 76.5% - - Saito 2013 - - - 67.6% - Rapoport 2015 (HEC-1) - - - - 75% Rapoport 2015 (HEC-2) - - - - 71% AC Schwartzberg 2019 82.5% 86.1% - - - Aapro 2014 - 79.8% - - - Warr 2005 - - 76% - - Schwartzberg 2016 - - - - 72.4% Conclusions Both IV and oral formulations of NEPA along with DEX represent highly effective guideline-compliant single-dose antiemetics. Clinical trial identification NCT03403712. Editorial acknowledgement Jennifer Vanden Burgt, Minneapolis, MN, funded by Helsinn Healthcare, Lugano, Switzerland. Legal entity responsible for the study Helsinn Healthcare. Funding Helsinn Healthcare. Disclosure L. Schwartzberg: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare ; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: Merck ; Advisory / Consultancy: Heron. M.S. Aapro: Advisory / Consultancy, Research grant / Funding (institution): Helsinn Healthcare; Advisory / Consultancy: Mundipharma; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: G1 Therapeutics.

Background Chemotherapy Induced Nausea and Vomiting (CINV) is a common phenomenon and various modalities are being looked to reduce this adverse event. Though these modalities better control emesis, nausea is still a problem that is not optimally controlled, thus requiring newer methods to control the same. Methods In this study, various combinations of Olanzapine (O), Aprepitant (A), Dexamethasone (D) and 5-HT3 Antagonist (H) were randomized to three groups - standard (AHD), combined (AHDO) & olanzapine (HDO) and compared for efficacy to address the problem of CINV. Patients who had never had any previous chemotherapy and receiving cisplatin, cyclophosphamide–doxorubicin & any other Highly Emetogenic Chemotheraphy (HEC) as per guidelines were enrolled. The standard doses of the concomitant drugs were administered before and after chemotherapy. The two groups receiving Olanzapine were administered 10 mg orally daily on days 1 through 4. Nausea prevention & complete response (no emesis, no use of rescue medication) were primary end points. The toxicity profile and quality of life were secondary end points. Results Total of 209 subjects were included in this study (68 in standard (A), 70 in combined (B) & 71 in olanzapine (C) arm). The proportion of patients with no chemotherapy induced nausea was significantly greater in group B than in C & A arm for first 24 hours after chemotherapy (80% (B) v/s 63.23% & 58.9% (AC p Conclusions Addition of Olanzapine to the standard arm significantly improved nausea prevention, as well as the complete response for vomiting. This modality may be further studied to determine its efficacy in lower doses so as to negate the effect of sedation. Legal entity responsible for the study Kidwai Cancer Institute. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone. Patients and methods Patients receiving chemotherapy including cisplatin (≥70 mg/m2) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 mg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1–3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0–120 h). Results The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0–24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24–120 h postchemotherapy) phase (65% versus 49%, P = 0.0025). Conclusions Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin.

The implications of chemotherapeutic drug-drug interactions can be serious and thus need to be addressed. This review concerns the potential interactions of the antiemetic aprepitant, a neurokinin-1 receptor antagonist indicated for use (in Europe) in highly emetogenic chemotherapy and moderately emetogenic chemotherapy (MEC) in combination with a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and corticosteroids and (in the United States) in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin. When considering use of aprepitant for prevention of chemotherapy-induced nausea and vomiting, its potential drug-drug interaction profile as a moderate inhibitor of cytochrome P-450 isoenzyme 3A4 (CYP3A4) has been a source of concern for some physicians and other health care professionals. We explore in this paper how real those concerns are. Our conclusion is that either no interaction or no clinically relevant interaction exists with chemotherapeutic agents (intravenous cyclophosphamide, docetaxel, intravenous vinorelbine) or 5-HT3 antagonists (granisetron, ondansetron, palonosetron). For relevant interactions, appropriate measures, such as corticosteroid dose modifications and extended International Normalized Ratio monitoring of patients on warfarin therapy, can be taken to effectively manage them. Therefore, the concern of negative interactions remains largely theoretical but needs to be verified with new agents extensively metabolized through the 3A4 pathway.

We aimed to investigate the efficacy of 0.25 mg dose of palonosetron and granisetron in triplet antiemetic prophylaxis in breast cancer patients receiving HEC. Patients with nonmetastatic breast cancer who received HEC [doxorubicin or epirubicin plus cyclophosphamide (AC/EC)] were enrolled in the study. The prophylactic triplet antiemetic regimens were used according to the doctor’s preference during the first cycle of HEC as intravenous dexamethasone and palonosetron 0.25 mg or granisetron 3 mg on day 1 as well as oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3).The primary endpoint was complete response rate (CR) on acute and delayed chemotherapy-induced nausea and vomiting (CINV), separately. A total of 118 female patients were included in the study. Patients received AC (83%), EC (3%), and dose-dense AC (14%) as adjuvant (88%) or neoadjuvant (12%). The majority of patients received palonosetron (59%) containing antiemetic treatment. The CR rate on acute and delayed vomiting was very high and not statistically different in both of the arms (acute 87% vs. 96%, p = 0.089; delayed 90% vs. 92%, p = 0.489), respectively. Nevertheless, the CR rate on either acute or delayed nausea was lower than vomiting (acute 51% vs. 51%; delayed 38% vs. 29%, p = 0.203; respectively). This is the second study that compared a 0.25 mg dose of palonosetron with first-generation setron in triplet antiemetic prophylaxis in cancer patients receiving HEC. We could not find meaningful statistical differences between two arms, regarding CR rate on acute and delayed CINV.

Background We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days. Patients and methods Patients scheduled to receive cisplatin ≥70 mg/m2 were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2–3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1–4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1–5 post-cisplatin). Results Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2–5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P ≤ 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P ≤ 0.001). Rates of no rescue therapy were similar between groups. Conclusions Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC00090207

Background: Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new, efficacious antiemetic drugs. Methods: A critical review of the results of published studies of aprepitant, a new NK1 receptor antagonist, and of palonosetron, a 5-HT3 receptor antagonist with a longer half-life. Results: Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increased the control of acute emesis with respect to dexamethasone and a 5-HT3 antagonist alone after cisplatin and moderately emetogenic chemotherapy. For cisplatin nausea, aprepitant combined with dexamethasone significantly increased the control of delayed emesis with respect to dexamethasone alone, while for moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist in the control of delayed emesis. Palonosetron showed superior or similar efficacy to ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted to cisplatin. Conclusions: More studies are necessary comparing aprepitant alone or combined with dexamethasone with respect to the recommended antiemetic drugs for the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy as well as for palonosetron combined with dexamethasone with respect to other 5-HT3 antagonists combined with dexamethasone.

In the late 1990s, several professional organizations convened antiemetic guideline groups and published the findings of these expert panels. Each of these documents was based on analyses of the available published trials and provided nearly similar recommendations. Nonetheless, small differences in emetic risk categories and treatment recommendations led to confusion in antiemetics selection. With the emergence of new findings and agents since the guidelines were initially published, many of the oncology professional societies have updated the antiemetic guidelines.A literature review up to March 2004 was carried out using MEDLINE with evaluation of the evidence by an expert panel composed of 23 oncology professionals in clinical medicine, medical oncology, radiation oncology, oncology nursing, statistics, pharmacy, medical policy and decision making, and pharmacology. The experts represented nine oncology professional societies and came from 11 different countries on four continents.Recommendations on antiemetic regimens to prevent emesis induced by high, moderate, low and minimal risk chemotherapy were suggested as well as management of anticipatory emesis. Furthermore, recommendations for refractory emesis, emesis induced by high-dose chemotherapy and radiotherapy and for antiemetics in children receiving chemotherapy were elaborated.Recommendations about antiemetic prophylaxis in patients receiving treatment with chemo- and radiotherapy have been updated by representatives of nine oncological organizations.

Introduction Itching is a common dermatologic side effect of anti-epidermal growth factor receptor antibodies and tyrosine kinase inhibitors and may have a dramatic impact on patients' quality of life. Aprepitant, a neurokinin receptor inhibitor, showed efficacy in treating refractory pruritus. We designed a pilot single-center phase-II study evaluating the effects of aprepitant in managing biological therapy-induced pruritus. Methods Forty-five cancer patients treated with biological therapies were enrolled and divided in: 1) patients affected by itch refractory to standard treatment (“refractory-group”) and 2) patients who did not receive any treatment for pruritus (“naive-group”). The intensity of itch was evaluated with Visual Analogue Scale (VAS)-score. All included patients had severe pruritus (VAS-score ≥ 7). In the refractory group aprepitant (125 mg on day 1; 80 mg on day 3 and on day 5) was administered after at least 1-week of standard systemic treatment (steroid and/or antihistaminics). In the naive-group aprepitant was administered, with the same schedule, after first severe pruritus onset. Results Forty-five (25 males and 20 females) patients were enrolled, 24 in the refractory group and 21 in the naive-group. The median age was 64 years. Among the enrolled patients, 38% (n = 17) were affected by lung cancer, 44% (n = 20) by colorectal cancer, and 18% (n = 8) by other tumors. Severe itching occurred in 16 patients treated with erlotinib, 23 with cetuximab, 1 with lapatinib, 3 with sunitinib, 1 with imatinib and 1 with gefitinib. The median decrease in pruritus intensity at 1-week after aprepitant introduction was 93% (p Conclusions This single-center phase-II study showed a new therapeutic activity of aprepitant in treating biological therapy-induced pruritus, both after standard antipruritic-medication failure and as a first-line therapy. Disclosure All authors have declared no conflicts of interest.

Background: Chemotherapy-induced nausea and vomiting (CINV) are one of the most unpleasant non-haematological adverse effects that affect the well-being of cancer patients. The aim of this study was to evaluate the association between the antiemetic efficacy and the ABC genetic polymorphisms and clarify the risk of CINV. Methods: Patients receiving highly emetogenic chemotherapy were examined for antiemetic responses to aprepitant in combination with granisetron and dexamethasone. The efficacy endpoint of this study was complete response (no vomiting and no use of rescue medications). Patient DNA samples were genotyped for ABCB1 and ABCG2 single nucleotide polymorphism. In this study, the impact on complete response of treatment and a number of prespecified risk factors, including gender, age, performance status (PS) and alcohol use was assessed. Complete response and the associations with patients factor including genetic polymorphisms were evaluated in acute and in delayed phases using univariate and multivariate analyses. Results: Sixty-eight patients receiving doxorubicin plus cyclophosphamide chemotherapy and 30 patients receiving cisplatin containing chemotherapy were evaluated. The multivariate logistic regression analyses showed that female gender (odds ratio [OR], 7.17; 95% confidence interval [CI] 1.43-35.82), age Conclusions: In addition to gender and age known to be risk factors for CINV, ABC transporter polymorphisms may influence the extent of acute CINV control in aprepitant, granisetron and dexamethasone-treated patients. ABC genotypes might be a predictor of antiemetic response in acute phase.

Chemotheraphy-Induced Nausea and Vomiting in cancer (CINV) is a factor which significantly reduces the quality of life (QOL) of patients by physical pain and emotional distress. For the purpose of making appropriate supportive care, “antiemetics proper use guidelines” was created in 2010.It has become possible to use granisetron and aprepitant, palonosetron from 2010 in Japan. In recent years, studies of antiemetics has been studied, but studies on the chemotherapy of hematopoietic malignancies still low. We thought in the chemotherapy of hematopoietic malignancies, and you want to consider the supportive care more effective. We have compared the effect of palonosetron and granisetron in consolidation therapy and remission induction of Acute Myeloid Leukemia. The incidence of nausea Grade 2 or more of acute, 24/47 cases of granisetron group (51%), 12/40 cases of palonosetron group (30%) P = 0.053. The incidence of nausea Grade 2 or more of Delayed 15/47 cases of granisetron group (32%), 7/40 cases of palonosetron group (30%) P = 0.144, As explained above and tended to the incidence of nausea Grade 2 or more of palonosetron group is small. However, both showed no significant difference. Comparing the price of each formulation, granisetron 3mg pack is 2874 yen, palonosetron 0.75mg is 14,522 yen. Granisetron be cheaper as unit price, but palonosetron be cheaper in the administered regimen consecutive days for one week before and after. Therefore, for the use of antiemetics in the treatment of acute myeloid leukemia, resulted palonosetron group is superior in cost-effective.

Purpose: There is room for discussion of the optimal method of antiemetic therapy in moderately emetogenic chemotherapy (MEC). We compared palonosetron (Palo) and Dexamethasone (Dex) with fosaprepitant (Fapr), granisetron (Gran) and Dex as antiemetic therapies in MEC. Methods: We enrolled 15 patients who underwent the MEC for the first time in our hospital between April 2013 and January 2014. Participants were randomized to the group preceding Fapr + Gran + Dex therapy and Palo + Dex therapy as a cross-over design. The patients underwent both therapies at the end of the second course. On day 1, we administrated Fapr 150mg, Dex 4.95mg, Gran 3mg in the Fapr + Gran + Dex therapy, and Palo 0.75mg, Dex 9.9mg in the Palo + Dex therapy. We used the Japanese version of MAT (MASCC Antiemesis Tool), and evaluated mainly the Complete Response rate of vomiting (CR rate) of every day for 5 days from the start of the treatment. We also evaluated the Complete Control rate of emetic events (CC rate) and the Total Control rate of nausea and vomiting (TC rate). Results: Full 5 day CR rates were 66.7% (Palo + Dex therapy) and 73.3% (Fapr + Gran + Dex therapy) (P = 0.690). CC rate were 53.3% and 66.7% (P = 0.456), TC rates were 46.7% and 60.0% (P = 0.464). We observed a tendency of Fapr + Gran + Dex therapy being better than Palo + Dex therapy in all evaluation points. Conclusion: It has been suggested that the three-drug combination therapy of Fapr + Gran + Dex might be superior to the two-drug combination therapy including Palo as antiemetic therapy in MEC. We will continue collecting data and studying the problem in more detail.

Background: Introduction of oral fluoropyrimidine eliminates the need for central vein catheter placement in patients who receive fluoropyrimidine-containing regimen. However, patients some time experience phlebitis attribute to administration of agents other than fluoropyrimidine through peripheral vein. Methods: The incidence of phlebitis was investigated in 80 patients with colorectal cancer who were treated with oral fluoropyrimidine plus oxialiplatin or irinotecan regimens through peripheral vein between January 2013 and December 2013. All data were retrospectively collected from the electronic medical record system. Results: The phlebitis was observed in 13 of 80 patients (16.3%) including induration in 12, redness in 4 and pain in 3. All phlebitis cases were defined as grade 1 by Common Terminology Criteria for Adverse Events version 4.0. None of them postponed the treatment due to phlebitis. The phlebitis improved in 11 of 13 patients. Fosaprepitant Meglumine was used in higher number of patient who developed phlebitis in comparison to these who did not (92.3% vs. 52.2%, p Conclusions: The significant number of patients development phlebitis when oral fluoropyrimidine plus oxialiplatin or irinotecan was given through peripheral vein, but all of them were mild. Intravenous administration of fosaprepitant might be involved in the development of phlebitis.

Aim: As emesis is more difficult to suppress once it occurs, preventing chemotherapy-induced nausea and vomiting from the initial cycle through repeated cycles is essential for an optimal patient-centered approach to cancer management. NEPA is a novel, fixed-dose combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA is designed to overcome barriers hindering guideline adherence by targeting two molecular pathways with a single, oral fixed-dose product. NEPA was previously shown to be superior to PALO after a single chemotherapy (CT) cycle; maintenance of efficacy over multiple cycles has been evaluated in a combined dataset from 2 pivotal trials. Methods: These large multinational, randomized studies assessed the efficacy/safety of a single oral dose of NEPA (vs PALO or aprepitant+PALO) in chemotherapy-naive patients receiving multiple cycles of either anthracycline-based (AC) moderately emetogenic CT (MEC) [study 1] or non-AC based MEC or highly emetogenic CT (HEC) [study 2]. All patients also received oral dexamethasone (DEX). Efficacy endpoints were complete response (CR: no emesis, no rescue) and no significant nausea (max Results: 1033 NEPA-treated patients participated in 4428 total cycles in these two trials; 76% completed at least 4 cycles. Overall CR and no significant nausea rates were high and were maintained across 4 cycles of CT with rates being modestly lower in patients receiving AC MEC compared to non-AC MEC and HEC. CR No Significant Nausea (N=AC/non-AC/HEC) AC MEC Non-AC MEC HEC AC MEC Non-AC MEC HEC Cycle 1 (N=724/235/74) 74% 80% 84% 75% 85% 82% Cycle 2 (N=635/212/68) 80% 88% 79% 77% 87% 87% Cycle 3 (N=598/196/63) 84% 91% 91% 78% 89% 92% Cycle 4 (N=551/181/52) 84% 92% 85% 80% 94% 85% The type/incidence of AEs was typical for a diverse cancer population receiving chemotherapy and raised no safety concerns. Conclusions: This is the largest multiple cycle dataset for an antiemetic and provides confidence in the preservation of benefit with NEPA over multiple cycles of AC- and non-AC MEC and HEC. NEPA, a highly convenient, guideline-based antiemetic combination may result in greater adherence and consequently improved emetic control. Disclosure: M.S. Aapro: Consultant, Research Funding, Honoraria: Helsinn Healthcare; R. Gralla: Consultant: Helsinn Healthcare and Eisai Inc.; M. Karthaus: Consultant: Helsinn Healthcare; L. Schwartzberg: Consultant: Helsinn Healthcare & Eisai Inc.; G. Rossi: Employee: Helsinn Healthcare; G. Rizzi: Employee: Helsinn Healthcare; M.E. Borroni: Employee: Helsinn Healthcare; M. Palmas: Employee: Helsinn Heathcare; H.S. Rugo: Consultant and Research Funding: Helsinn Healthcare; K. Jordan: Consultant and Honoraria: Helsinn Healthcare, Merck.

Aim: This analysis aimed at describing the usage of antiemetic treatments (tx) to prevent chemotherapy-induced nausea and vomiting (CINV) in the acute onset across EU5 countries (France, Germany, Italy, Spain, United Kingdom). CINV is known to be one of the most distressful side effects in over 70% of patients (pts) receiving chemotherapy (ct) and can be prevented in up to 70-80% of pts. The emetogenic potential (ep) of the chemotherapeutic agents used is the main risk factor for developing CINV. Methods: This study is based on IMS Oncology Analyzer™, a quarterly physician panel survey that provides a broad perspective of cancer pts care, across all cancer types and treatment modalities. Pts receiving a ct (defined at ATC L1 EphMRA classification) were analyzed from Jan to Dec 2013 in EU5 countries. Projected estimates for the number of pts currently being treated were provided. Results: The antiemetic tx (aet) patterns are summarized in the table. 35'874 pts (representing a total treated prevalence of 2'027'394 pts) were identified as currently receiving a ct. Overall, only 52% of those pts received an aet. Among them, 65% of pts received either a setron (setr) or aprepitant (apr) in the first day of ct administration. In that population 2.5% of pts received a combination of both palonosetron (palon) and apr. In 61% of cases this combination was used in breast cancer. Antiemetic tx patterns - 2'027'394 ct treated pts in EU5 High Moderate Moderate AC * Non-AC * ep of ct** (20%) (8%) (32%) Apr d1 15% 18% 4% apr mono 20% 22% 24% + palon 10% 28% 6% + other setr 69% 50% 71% Setr d1 no apr 39% 35% 44% palon 7% 18% 7% other setr 93% 82% 93% No setr/apr d1 but other aet 3% 3% 4% aet not d1 13% 9% 18% No aet 30% 35% 31% * Only breast cancer, AC: anthracycline (doxorubicin/epirubicin) + cyclophosphamide ** 34% of pts treated with low or minimal emetogenic ct, 6% of pts with unknown emesis risk. Conclusions: This analysis shows that there is still a significant lack of prophylactic aet. Currently, only about 12% of pts receiving high emetogenic ct, 14% of pts receiving AC and 47% non-AC pts are treated according to antiemetic guidelines (MASCC/ESMO 2013). Further research is necessary to understand the barriers to guideline adherence in clinical practice. Disclosure: All authors have declared no conflicts of interest.

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

Aim: Aprepitant, a neurokinin 1 antagonist, showed efficacy for chemotherapy-induced nausea and vomit(CINV). Antiemetic guidelines recommend aprepitant for high emetogenic chemotherapy(HEC). This prospective, randomized, cross-over trial aimed to evaluate the efficacy of aprepitant for patients(pts) receiving moderate emetogenic chemotherapy(MEC). Methods: Gastrointestinal cancer pts receiving MEC were randomly assinged to GroupA and B. We administered as follows; in GroupA; on first course, pts received palonosetron (0.75mg iv on day 1) and dexamethasone (9.9mg on day 1, and 8mg p.o. on days 2-3) (control premedication) and on second course, pts received oral aprepitant (125mg on day 1 and 80mg on days 2-3) with control premedication (dexamethasone; 4.95mg iv and 4mg p.o.). In GroupB, pts received aprepitant with control premedication on the first course and they received control premedication on second course. The primary endpoint was rate of CR (complete response; neither emesis nor rescue therapy) and degree of nausea. Results: From January 2011 to March 2013, 100 pts were enrolled, and 83 pts were analyzed(female/male, 35/48; median age, 65 years; colorectal/gastric, 64/19; irinotecan/oxaliplatin 53/30). The CR rates of aprepitant/control were 73.5%/60.2%(p = 0.064). The degree of nausea was(more than intermediate) was 4.9%/19.0%(p = 0.02). Conclusions: Adding aprepitant significantly reduced moderate and severe emesis compared with standard premedication. Although the rate of CR was not statistically significant, aprepitant reduced the degree of nausea. Adding aprepitant is promising for gastrointestinal cancer pts receivig MEC. Disclosure: All authors have declared no conflicts of interest.

Aim: Aprepitant is a new neurokinin-1 receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). Several reports have shown that aprepitant is very effective for the prevention of CINV with highly emetogenic chemotherapy (HEC) in cisplatin-based regimens. However the efficacy of aprepitant for moderately emetogenic chemotherapy (MEC), such as paclitaxel plus carboplatin (TC), is still unclear. We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese gynecologic patients who received a TC regimen. Methods: This phase III, randomized, double-blind study enrolled patients from nine institutions with a diagnosis of ovarian, endometrial, or cervical cancer who were scheduled to receive paclitaxel (175-180mg/m2) and carboplatin (AUC=5-6) for the first time. Patients received aprepitant or placebo with a 5-HT3 antagonist (except palonosetron) and dexamethasone before chemotherapy. Patients recorded nausea and vomiting episodes in a diary. Endpoints were proportions of patients with no vomiting, no significant nausea and complete response ( no vomiting and no rescue medication) for five days after chemotherapy. Results: Of 324 randomized patients, 297 patients (151 in the aprepitant group; 146 in the placebo group) were evaluable for efficacy and toxicity. The percentages of patients with no vomiting (84.8% vs 61.6%, p Conclusions: The combination of aprepitant, a 5-HT3 antagonist, and dexamethasone demonstrated efficacy for CINV prevention with MEC in patients with gynecologic cancer receiving a TC regimen. Disclosure: All authors have declared no conflicts of interest.

– In the primary analysis from this study, treatment with aprepitant resulted in a greater proportion of patients achieving complete response (CR) in the delayed phase (25–120 hours after chemotherapy initiation) than the standard regimen alone (51% vs 26%, P < 0.0001) 7 • CR was defined as “no vomiting or retching and no use of rescue medication” – CR was also greater with the aprepitant regimen vs the control regimen in the acute (66% vs 52%; P = 0.0135) and overall phases (40% vs 20%; P = 0.0002) 7

Aim: Aprepitant, in combination with a 5HT3-antagonist and a corticosteroid, is indicated for prevention of CINV due to highly/moderately emetogenic chemotherapy (chemo) in adults. To evaluate aprepitant for CINV prevention in children, a phase III, randomized, double-blind, active-comparator study was conducted in pediatric patients (NCT01362530). Methods: Patients ages 12-17 years (y) undergoing highly/moderately emetogenic chemo received aprepitant capsule 125 mg + ondansetron before chemo (Day 1) + aprepitant capsule 80 mg (Days 2-3), OR placebo (Days 1-3) + ondansetron (Day 1). Patients 6 months to Results: Efficacy and safety were evaluated in 152 aprepitant and 150 control patients. The proportion of patients experiencing no emetic episodes was higher in the aprepitant regimen vs the control regimen during both acute (71.1% vs 53.3%) and delayed (55.3% vs 28.0%) phases. The median time to first vomiting (overall) was significantly longer for aprepitant vs control (94.5 vs 26.0 hours; P Conclusions: In pediatric patients with cancer receiving emetogenic chemo, the 3-day aprepitant regimen prevented emetic episodes and reduced the need for rescue medication compared with a 5HT3-antagonist regimen without aprepitant. Disclosure: H.J. Kang: Received research funding from Merck & Co., Inc. MK869 PN208 study involvement; S. Loftus: Full-time employee of Merck & Co., Inc., with stock ownership; A. Taylor: Full-time employee of Merck & Co., Inc.; C. Dicristina: Full-time employee of Merck & Co., Inc.; S. Green: Full-time employee of Merck & Co., Inc., with stock ownership. All other authors have declared no conflicts of interest.

Aim: Few side effects of chemotherapy are more feared by patients than nausea and vomiting (CINV). For certain patients, it causes distress, morbidity and in some cases hospital admission. CINV can be Anticipatory (as a conditioned response), Acute (within hours of chemotherapy and peaking in the first four to six hours) and Delayed (occurring 24hrs after treatment). The aim of this audit was to assess current prescribing practice and outcomes at one of Europe's major cancer centres, and to benchmark practice against established international guidelines from the MASCC/ESMO 2009 Perugia consensus. We were also interested in what proportion of patients required admission due to CINV. Methods: Prospective study of case notes and e- prescribing records of 360 patients from four primary cancer disease sites (Head and Neck, Breast, Colorectal, and Ovarian). Each cohort was followed through three cycles of chemotherapy. Data on severity of nausea and vomiting, anti-emetic use, hospital admission and concordance with international guidelines was recorded. Results: Concordance with MASCC guidelines ranged from 88% (Head and Neck) to 0% (colorectal and ovarian. 57% of the total cohort reported nausea and 32% vomiting. 11% of patients were admitted to hospital with CINV a contributory factor. Aprepitant was added at a later cycle in 15% patients, which resulted in better symptom control. Conclusions: The objective of antiemetic therapy is the complete prevention of CINV. Treatment should individualise to the patient's regime, and other factors such as physical and psychological comorbidity. Patients should have access to information and alternative treatments. Admission as a consequence of CINV should be considered as a treatment failure. Where control is poor other causes such as CNS or gastrointestinal pathology, metabolic problems, and drugs should be considered prior to changing antiemetics. In our Centre the introduction of MASCC guidance, comprehensive clinical assessment prior to and after the first cycle (with the early addition of aprepitant for symptomatic patients), could reduce debilitating symptoms, improve QOL, and reduce unnecessary admissions. Disclosure: All authors have declared no conflicts of interest.

Aim: FOLFIRINOX has proven effective in advanced PDAC. In order to overcome toxicity issues, dose/schedule modifications and additional supportive measures are being considered. Methods: We reviewed the clinical charts of 270 PDAC pts receiving classic FOLFIRINOX (group 1) or mFOLFIRINOX (group 2) at 7 Italian Institutions. Results: Patient characteristics are shown in the table. Fifty seven pts/590 cycles and 213 pts/1127 cycles were available for analysis in groups 1 and 2, respectively. Overall toxicity was mild; significant differences in G2-4 toxicities between the two groups: asthenia (10% vs 6%, p = 0.001), diarrhea (7% vs 4%, p = 0.01), and thrombocytopenia (4% vs 0.5%, p N. of Pts (%) Pts 270 Median age (range) 59 yrs (37-76) M/F 146 (54) / 124 (46) ECOG PS 0 1 2 na 189 (70) 75 (28) 7 (1) 3 (1) T location head body-tail 132 (49) 138 (51) Stage I-II III IV 21 (8) 86 (32) 163 (60) Biliary Stent 57 (21) Biliopancreatic derivation 31 (12) Folfirinox schedule classic (group 1) modified (group 2) 82 (30) 188 (70) Locoregional treatment for inoperable disease 36 (13) Second line chemotherapy 120 (44) Conclusions: FOLFIRINOX/mFOLFIRINOX are well tolerated and easily manageable on an outpatient basis and can be safely used in pts carrying biliary stents. Differences in toxicity and efficacy with modified schedules deserve further investigation. Disclosure: All authors have declared no conflicts of interest.