Antiemetic Therapy Research Articles

Antiemetic Effectiveness and Cost-Saving of Aprepitant plus Granisetron Is Superior to Palonosetron in Gastrointestinal Cancer Patients Who Received Moderately Emetogenic Chemotherapy.

Purpose The therapeutic benefit of a three-drug combination of antiemetics has not been established in moderately emetogenic chemotherapy (MEC). The aim of this study was to compare the antiemetic effectiveness and cost-saving of palonosetron plus dexamethasone (control group) with aprepitant, granisetron, and dexamethasone (study group) in cancer patients who received MEC.Methods We switched the standard antiemetic treatment from the control group to the study group in gastrointestinal cancer patients who received MEC after October 2015. The antiemetics in both groups were modified using salvage antiemetic therapy at the clinicians' discretion, according to the severity of chemotherapy-induced nausea and vomiting. We retrospectively reviewed the electronic medical records from patients, before and after switching groups, from between April 2014 and March 2016.Results We evaluated 443 treatment courses in 83 patients. The proportion of courses that included salvage antiemetic therapy in the control group and the study group was 34.8 % (116/333) and 8.2 % (9/110), respectively, and was statistically significant (p < 0.001). The mean integrated costs of antiemetics per course in the control group and the study group were 193 ± 55 USD and 143 ± 38 USD, respectively. Multivariate logistic regression analysis revealed that the study group was significantly associated with a reduced risk of requiring salvage antiemetic therapy (p = 0.038).Conclusions These results suggest that the antiemetic effectiveness and cost-saving of a three-drug combination of aprepitant, generic granisetron, and dexamethasone was superior to a two-drug combination of palonosetron plus dexamethasone in gastrointestinal cancer patients who received MEC.

The preventive effect of the impaired liver function for antiemetic therapy against chemotherapy-induced nausea and vomiting in hepatocellular carcinoma patients.

Transarterial chemoembolization and hepatic arterial infusion chemotherapy are recommended for the treatment in patients with intermediate stage of hepatocellular carcinoma. Impaired liver function was sometime observed in patients with hepatocellular carcinoma after transarterial chemoembolization or hepatic arterial infusion chemotherapy. However, what kinds of factors deeply influence in impaired liver function are not clear. A retrospective study was performed to evaluate the risk factors of impaired liver function in cisplatin-naïve patients treated with these therapies using cisplatin. Prior to and 2 months after these therapies, we analyzed the liver function by Child-Pugh score in these patients. For assessing the severity of chemotherapy-induced nausea and vomiting, we utilized the Common Terminology Criteria for Adverse Events ver. 4.0. In hepatocellular carcinoma patients received these therapies using cisplatin, the cancer stage and treatment without neurokinin-1 (NK1) antagonist were found to be independent risk factors of the impaired liver function. The treatment with NK1 antagonist was effective in reducing chemotherapy-induced nausea and vomiting and patients treated with NK1 antagonist kept their liver functions after cisplatin-used these therapies. The treatment with NK1 antagonist was effective in chemotherapy-induced nausea and vomiting and prevented the impaired liver function associated with cisplatin-used these therapies in hepatocellular carcinoma patients.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

Background/Aims: Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

P3.05-007 Prospective Evaluation for Combination Antiemetic Therapy on CINV in NSCLC Receiving Carboplatin-Based Chemotherapy of MEC: Topic: Symptoms, Therapeutic Interventions

The incidence of delayed chemotherapy-induced nausea and vomiting (CINV) for non-small cell lung cancer (NSCLC) patients receiving carboplatin (CBDCA) -based chemotherapy (CBDCA+pemetrexed (PEM) / CBDCA+ paclitaxel (PTX)) has not been clearly controlled. We used the combined data from the two prospective observational studies; A nationwide survey of CINV study group and the other prospective observational study in Japan. We assessed whether delayed CINV were controlled with combination antiemetic treatment. We also evaluate risk factors by logistic regression analysis. A total of 240 patients were evaluable in this study. The median age was 66 (range: 34-82) with 173 males and 67 females. Three antiemetics were used in 54 (22.5%) patients. Delayed nausea and vomiting were experienced more commonly in women than in men. Delayed nausea was well controlled with 3 antiemetics than with 2 antiemetics for women (45.0% vs. 72.3%; P=0.0506). Delayed vomiting was well controlled with 3 antiemetics than with 2 antiemetics for overall (11.1% vs. 23.1%; P=0.0571) and for women (20.0% vs. 44.7%; P=0.0962). We identified several risk factors; women (OR=2.903; 95% confidence interval [CI], 1.607-5.242; P=0.0004) and age (OR=0.968; 95% CI, 0.938-0.999; P=0.0442) for delayed nausea, and women (OR=4.252; 95%CI, 2.154-8.394; P<0.0001) and 2 antiemetics (OR=3.140; 95%CI, 1.205-8.179; P=0.0192) for delayed vomiting. Three antiemetics combination are encouraged for NSCLC patients treated with CBDCA-based chemotherapy to alleviate delayed vomiting.

Chemotherapy-Induced Nausea and Vomiting (CINV) in Hematologic Malignancy Patients Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC)

INTRODUCTIONDespite recent advances in CINV prophylaxis, many questions remain unanswered including optimal treatment for hematologic malignancy (HM) patients receiving multi-day chemotherapy regimens. As preparation for stem cell transplant (SCT) and for high grade HM, highly emetogenic chemotherapy (HEC) containing regimens are often utilized. International guidelines recommend a three-drug combination of a 5-HT3receptor antagonist (5-HT3 RA), an NK-1 receptor antagonist (NK-1 RA) and dexamethasone (dex) before HEC. Little is known about CINV prevention in HM multi-day regimens.METHODSWe conducted a prospective observational study in U.S. research centers with expertise in HM and SCT surveying providers and adult patients receiving up to 7 consecutive days of chemotherapy including at least one HEC drug. Those receiving concurrent radiation therapy were excluded as were patients taking antiemetics or having nausea and vomiting prior to initiation of chemotherapy. Patients completed a diary and a modified Functional Living Index - Emesis (FLIE) questionnaire daily, beginning at screening, during chemotherapy, and for up to 5 days after the last day of treatment. Daily use of scheduled antiemetics and rescue medication was collected. The primary objective was to survey patterns of CINV care for multi-day chemotherapy in HM and assess efficacy of the intervention.RESULTSSeventy-six patients were enrolled at 5 centers (range 8 -25 patients per center) between May 2015 and February 2016. Of the patients, 72 underwent pre-SCT conditioning and 4 multi-day chemotherapy for HM. Forty-nine (68%) were male and 58 (81%) were Caucasian; median age was 58 (range 22-74). The most common diagnoses were NHL, 27 (36%); multiple myeloma, 19 (25%); and AML, 15 (20%). Seventy-one patients completed all surveys. All received ≥ 1 HEC drug on day 1. The most common chemotherapy regimens were BEAM, 28 (37%), high-dose melphalan, 18 (26%), melphalan, fludarabine, and campath, 8 (11%) and fludarabine and cyclophosphamide, 4 (5%). Anti-emetic therapy was highly variable, both prior to day 1 chemotherapy and throughout multi-day treatment. On day 1 the most common regimens included: a combination of 5-HT3 RA, NK-1 RA, dex in 28 (37%); 5-HT3 RA + dex in 24 (32%); 5-HT3 RA alone in 9 (12%); 5-HT3 RA and metoclopramide in 2 (3%); other 10 (13%) and none documented 3 (4%). Complete response rate (defined as no vomiting and no use of rescue medications) was observed in 15 patients (20%); complete response by day ranged from 95% on day 1 to 46% on end of study day (p=0.041). Mean±SD nausea scores by FLIE increased from 19.9±3.1 pretreatment to 22.4±3.3 overall (p=0.0031).CONCLUSIONApproaches to CINV in SCT and HM patients receiving multi-day HEC regimens are highly variable. A large majority of patients receiving multi-day chemotherapy are not achieving adequate control of nausea or vomiting. Additional clinical trials and development of evidence-based approaches to CINV prophylaxis in HM patients throughout multi-day chemotherapy are critical to improve supportive care. DisclosuresSchwartzberg:Helsinn: Consultancy, Research Funding; Eisai: Consultancy; Tesaro: Consultancy; Heron: Consultancy. Roeland:Teva: Speakers Bureau; Insys: Consultancy; Helsinn: Consultancy; Heron: Consultancy; AstraZeneca: Consultancy, Research Funding; Eisai: Speakers Bureau.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

BackgroundChemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among published guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assessed the efficacy and safety of triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy comprising palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication [complete response (CR)] in the acute phase (0–24 h), late phase (24–168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication [complete control (CC)].ResultsPrevalence of a CR during the acute phase, delayed phase, and overall was 100, 91.9 and 91.9%, whereas that of CC was 100, 84.4 and 84.4%, respectively. The most common adverse event was mild constipation; severe adverse events related to antiemetic treatment were not observed.ConclusionTriple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in the prevention of CINV in patients receiving a carboplatin-containing regimen.

Comparative Pharmacology and Guide to the Use of the Serotonin 5-HT3 Receptor Antagonists for Postoperative Nausea and Vomiting.

Since the introduction of the serotonin 5-hydroxy tryptamine 3 (5-HT3) receptor antagonists in the early 1990s, the incidence of postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) has decreased, yet continues to be a problem for the surgical patient. The clinical application of the 5-HT3 receptor antagonists has helped define the approach and role of these antiemetics in the prevention and treatment of PONV and PDNV. Pharmacological and clinical differences exist among these medications resulting in corresponding differences in effectiveness, safety, optimal dosage, time of administration, and use as combination and rescue antiemetic therapy. The clinical application of the 5-HT3 receptor antagonist antiemetics has improved the prevention and treatment of PONV and PDNV. The most recent consensus guidelines for PONV published in 2014 outline the use of these antiemetics. The 5-HT3 receptor antagonists play an important role to help prevent PONV and PDNV in perioperative care pathways such as Enhanced Recovery After Surgery (ERAS). Comparisons and guidelines for use of the 5-HT3 receptor antagonists in relation to the risk for PONV and PDNV are reviewed.

Predicting morphine related side effects in the ED: An international cohort study

Study objectivesMorphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid-related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs. MethodsIn this prospective, observational, pharmaco-epidemiological international cohort study, all patients aged 18years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid-induced ADRs within 6h after treatment. ResultsA total of 1128 patients were included over 10months. Median baseline initial pain scores were 8/10 (7–10) versus 3/10 (1–4) after morphine administration. Median titration duration was 10min (IQR, 1–30). The occurrence of opioid-induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01–2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29–6.51) were independent predictors of morphine related ADRs. ConclusionSerious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration.

The Ambulatory management of hyperemesis in a contemporary set up – an observational study of 386 women

Introduction: Nausea and vomiting in early pregnancy affect up to 90% of women, with 10,000 seek medical advice every year in the UK. The cost to the NHS in the year 2006/2007 was £41,815,000. The concept of “fast hydration protocol” in outpatient setting is a novel admission avoidance model to improve women's care and satisfaction, and reduce bed occupancy. This study evaluates the outcome of management of women with hyperemesis treated in a standalone contemporary “Emergency Gynaecology Unit” where outpatient fast hydration is offered as the first line management. Material and methods: The study included 386 women who presented to the “Emergency Gynaecology Unit” of a large teaching hospital, West Midlands, UK from 1st January 2014 till 12th December 2014. The data were extracted from the case notes to a predesigned profroma, and were analysed using Microsoft Access and Excel. Results: The majority of women were managed successfully in the outpatient setting only 36 (10%) required admission. The main indication of inpatient admissions was refractory hyperemesis not responding to fluid and anti-emetic therapy or coexisting indication such as gall stones. Of the 386 women, 239(62%) were multiparas, 190 (49%) presented at 8–12 weeks of gestation, 374 (97%) had singleton pregnancy on ultrasound scan, 271 (70%) required only one antiemetic drug, 292 (83%) received the standard 3 l of IV fluids as per the fast hydration protocol, and 270 (70%) represented to the unit for a repeat fast hydration (free access is given as part of the protocol). The main electrolyte abnormality noted was hypokalaemia (n = 46, 12%) which was treated with IV Potassium Chloride added to fluids. The majority of women 338 (96%) were fit for nurse discharge and the initial medical review was conducted in 248 (71%). Conclusion: Successful implementation of “fast hydration protocol” reduced admissions by 90%. Ambulatory management of hyperemesis in early pregnancy is safe, efficient, cost-effective and convenient to women. We are conducting a prospective patient survey to assess satisfaction with the service.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

226 Background: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assess efficacy and safety of triple antiemetic therapy consist palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Methods: Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy consist palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication (complete response (CR)) in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication (complete control (CC)). Results: Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Conclusions: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in preventing CINV in patients receiving a carboplatin-containing regimen. Clinical trial information: UMIN000017877.

Disparities in the availability of and access to antiemetics recommended by the international antiemetic guidelines in Serbia, Japan, and Nepal.

117 Background: Guideline-consistent antiemetic therapy requires 4 classes of antiemetics (AEs) to be available and accessible for the optimal prevention of chemotherapy induced nausea and vomiting (CINV): serotonin3 receptor antagonists (5HT3RAs), neurokinin 1 receptor antagonists (NK1RAs), dopamine receptor antagonists (DOPRAs) and dexamethasone. To evaluate disparities in the availability and accessibility of AEs recommended by the international antiemetic guidelines for the prevention of CINV inpatients treated in governmental hospitals in Nepal (low), Serbia (upper-middle) and Japan (high-income). Methods: Availability was evaluated by the formulary availability and marketing authorization (MA) in Serbia (RS), Japan (JP) and Nepal (NP). Accessibility was assessed by the National Health Insurance Fund (NHIF) coverage in Serbia and Japan and by the affordability in Nepal. Off-label use of medications is not legitimate in Serbia and Japan. Results: Barriers are presented in Table. Serbia has no access to NK1RAs and palonosetron for the prevention of CINV after HEC-AC and carboplatin. There are no barriers in Japan to provide all 4 classes of AEs. In Nepal all AEs are payed out of pocket and the guideline implementation completely depends on the affordability. Olanzapine is accessible in Nepal, but not in Japan and Serbia due to restricted off-label use of medications. Conclusions: The real life implementation of antiemetic guidelines for the prevention of CINV in various countries depends on the availability of and access to AEs recommended by the guideline. Identified barriers in Serbia and Nepal preclude physicians from providing optimal supportive care. [Table: see text]

Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers.

199 Background: Dronabinol, a pharmaceutical tetrahydrocannabinol (THC), capsule is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-induced nausea/vomiting in patients with inadequate response to conventional antiemetic therapy. Food effects on absorption and bioavailability of a new dronabinol oral solution was compared with marketed capsules. Methods: In an open-label, single-dose, 3-period crossover study, healthy volunteers were randomized to receive dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted), after a 7-day washout period. Doses were administered under a fasted (overnight) or fed state (high-fat/calorie meal 30 minutes pre-dose). Plasma pharmacokinetics was evaluated for dronabinol and the major metabolite, 11-OH-Δ9-THC. Results: Pharmacokinetic data of 54 volunteers were analyzed. In the fed state, initial dronabinol absorption was rapid with oral solution versus capsules (mean Tlag, 0.15 vs 2.02 h), and 100% and 15% of volunteers receiving oral solution and capsules, respectively, had detectable plasma dronabinol levels 30 minutes post-dose. Inter-individual variability in plasma dronabinol concentrations during early absorption was less with oral dronabinol solution (%CV: 82.79%, 83.94%, and 90.68%) versus capsules (%CV: 318.54%, 250.33%, and 182.01%) observed at 0.5, 1, and 2 h, respectively, after dosing. Food increased mean AUC0-t similarly for dronabinol oral solution and capsules, versus capsules with fasting, increasing exposure to oral solution and capsules 2.1- to 2.4-fold. Mean Tmax was similarly delayed for dronabinol oral solution (7.7 h) and capsules (5.6 h) with food relative to fasting (1.7 h). On the basis of 11-OH-Δ9-THC plasma levels, AUC0-t up to 48 h postdose and AUC0-inf were found to be similar for the oral solution and capsules under fed conditions. Conclusions: An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients given its rapid absorption and lower inter-individual variability compared with dronabinol capsules. Clinical trial information: NCT01448772.

1453P - Antiemetic prophylaxis (AP) in our clinical practice: are we doing it right?

In recent years several national and international guidelines about AP have been drafted; they suggest a different AP according to chemotherapeutic agents' emetic potential (that is, high [HEC], AC/EC regimen, moderate [MEC], low [LEC], or minimal [mEC]). We then decide to perform a survey to assess our adherence to these recommendations. We analysed AP prescribed to our patients (pts) who underwent chemotherapy (CT), both oral and intravenous, during 5 days in our Day Hospital Service. We compared it to 2016 MASCC Guidelines with the exception of carboplatin, which was still considered MEC (although the recent “upgrade” to HEC). We analysed 322 pts, of which 11 (3.4%), 11 (3.4%), 99 (30.8%), 126 (39.1%), and 75 (23.3%) received HEC, AC/EC, MEC, LEC, and mEC regimens, respectively. 82 pts (25.5%) received appropriate AP, whereas 240 (74.5%) had an inconsistent AP. Among HEC regimens, only 9.1% of pts received correct AP, whereas 91.9% had a wrong AP (70% in both acute and delayed AP). For AC/EC schemes, 100% pts received inconsistent AP, of which 36.4% in delayed AP, and 63.6% in both acute and delayed AP. Among MEC schemes, 96% pts received an inconsistent AP (45.3% in delayed AP, and 53.7% in both). For LEC schemes, 93.6% pts received inconsistent AP, among which 96.6% in acute AP. In mEC regimens, 92% pts received inconsistent AP (of which 66.6% in acute AP). The main errors are the abuse of corticosteroids, mainly in the acute AP (46.3% of all pts), and of anti-5HT3 (35.1%).Tabled 1Total (%)HEC (%)AC/EC (%)MEC (%)LEC (%)mEC (%)Consistent25.59.1046.392Inconsistent, of which: - Only acute - Only delayed - Both acute and delayed74.5 49.6 21.2 29.290.9 0 30 70100 0 36.4 63.696 1 45.3 53.793.6 96.6 0 3.48 66.6 16.7 16.7 Open table in a new tab Although the existence of specific AP guidelines, there is still a lack of adherence to evidence-based literature, both in the way of under- and over-prescription. This underlines the need of implementing education for healthcare professionals and usage of informatics tools for antiemetic therapies in everyday clinical practice to reduce inconsistencies and to increase adherence to guidelines.

Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemical stability, low cost, high purity, and versatility. However, the physical stability of niosomes, like other vesicular systems, is limited by vesicle fusion, aggregation, and leakage. Proniosomes (dehydrated powder or gel formulations that spontaneously form niosomes on hydration with aqueous media) can overcome these physical stability problems and are more convenient for sterilization, storage, transport, distribution, and dosing. Proniosomes have mostly been explored for their potential to enhance transdermal and oral absorption. In this study we assess, for the first time, the potential for hydrated proniosomes to sustain systemic exposure and therapeutic effect after intravenous delivery. Proniosomes carrying the anti-inflammatory drug, flurbiprofen, were prepared by spraying different nonionic surfactants (span 20, span 40, and span 60 in varying ratios with span 80) and cholesterol onto a sorbitol carrier. The proniosome powders were characterized for surface morphology and flow properties. Niosome formation was assessed at three different hydration temperatures (25, 37, and 45 °C), and the niosomes were assessed for vesicle size, entrapment efficiency, and sterility. OLP proniosomes prepared with a high ratio of span 80 to span 20 were found to spontaneously form vesicles of small size and high drug loading on hydration with aqueous media. The OLP derived niosomes successfully sustained in vitro drug release, in vivo pharmacokinetics, and the anti-inflammatory effect of flurbiprofen in an acute (rat paw edema) model of inflammation when compared to a control solution formulation. The study demonstrates that hydrated proniosomes can prolong systemic drug exposure over 3 days and provide a sustained therapeutic effect. The developed proniosomes represent a novel approach to treat acute pain and inflammation with the potential to be administered as a single intravenous dose by a clinician at the time of injury or surgery that provides adequate relief for several days and reduces fluctuations in therapy. Similar systems loaded with different drugs have potential for broader application in anesthesia, anti-infective, antiemetic, and cancer therapy.

Антиэметическая терапия раннего токсикоза у беременных с врожденными пороками сердца

Objective — to study the effectiveness of the Yunorm (Yuria-Farm) in the treatment of early severe toxicity in pregnant women with cardiovascular disease and anemia. Patients and methods. We examined 28 women with congenital heart disease and anemia who had received Yunorm (Yuria-Farm) intravenously by 2 ml (4 mg of ondansetron) per day (in severe cases twice a day) for the relief of emesis and nausea as a manifestation of moderate and severe early toxicity in pregnant women. Results. The high efficiency and safety of Yunorm (ondansetron) preparation, which was administrated intravenously for the treatment of nausea and vomiting during pregnancy is found. The safety of the use during gestation period was confirmed by the absence of significant side effects in women, significant changes in the fetus state and newborn. Conclusions. According to its safety profile ondansetron is qualified as B according to the FDA classification and can be recommended as an effective and safe anti-emetic preparation for use in obstetric practice. Key words: toxemia of pregnancy, cardiovascular disease, anemia, antiemetic therapy.

Effect of Acupressure on Nausea-Vomiting in Patients With Acute Myeloblastic Leukemia.

The aim of this study was to assess the effect of acupressure, applied at P6 (Neiguan) acupuncture point, on chemotherapy-induced nausea and vomiting in patients with acute myeloblastic leukemia. This was a randomized controlled trial conducted on patients with myeloblastic leukemia. A total of 90 patients, who received the same chemotherapy regimen and antiemetic therapy, were included in the study as 30 patients in the control group, 30 patients in the band group, and 30 patients in the pressure group. Although acupressure was applied by placing wristbands at P6 acupuncture point of both wrists in patients of the band group for totally 4 days, acupressure was applied with the use of finger pressure in patients of the pressure group for totally 4 days. No intervention was made in patients of the control group other than the routine antiemetic therapy. The data of the study were collected by using a questionnaire and nausea-vomiting chart. Severity of nausea-vomiting was assessed by using the visual analog scale on this chart. It was determined that the acupressure band applied to the patients included in the study reduced number and severity of nausea-vomiting (P < .05); however, the acupressure applied with pressure did not affect number and severity of nausea-vomiting (P > .05). It was found that the acupressure band was effective for reducing the chemotherapy-induced nausea and vomiting.

S51 - Oncogeriatric Unit: our experience

In developed countries, more than half of all tumor's cases occurs in patients aged 65 or more, for this reason a (multidisciplinary approach)combinated work between oncologist and geriatric is becoming more and more usefull in pratical oncology. At the same time, however, the oncological treatment results in elderly are far from satisfactory; treatment varies from therapeutic obstinacy to therapeutic abandonment. The understanding of elderly pantient condition and his needs become very important to allow healt, political and social strategies. Aim of the study: 150 patients were submitted to oncogeriatric evaluation, from February 2015 to March 2016. All were evaluatde for:-recognize patients fit for standard oncological treatments and patients in whome the risk of toxicity overcome potential benefits.-organize all medical, psycological and social support to improve treatment tolerance. Material and methods: all patients ( aged 65 or more) were screened with G8 (evaluation tool for geriatric patient); G8 allows to divide patients in 2 groups; those below the cut off score of 14 were sended oncogeriatric unit. Those with score 14 or more were sended directly to the oncology unit. We used CGA as instrument of geriatric evalutation. Results: 150 patients with a score <14 were sended for oncogeriatric evalutation; we identified 106 patients aged >65 that would have required chemoterapy (adiuvant and metastatic setting) 81/106 patients started chemioterapy with an adequate dose reduction (mono- or polychemotherapy) 25 resulted unfit for chemotherapy and were sended to palliative care unit. 52 well tollerated chemotherapy with adequate supportive therapy (myeloid stimulating factors, antiemetic therapy) toxicity was mild (1multifocal pneumonia an 1 anafilactic reaction) 27 patients dead after progression disease. no patient stopped treatment for toxicity, nor was hospitalized Conclusions: oncogeriatric evaluation is important to select patients fit for chemotherapy, getting better the clinical outcome, the management, the assistance and the therapeutical iter so reducing the frequency hospitalization.

Abstract PR377

Background & Objectives: Perioperative administration of carbohydrates is considered as one of the non pharmacological strategies to decrease PONV.However due to the variation in the dose, route and timing of administration of carbohydrate supplementation there has been conflicting results of it’s efficacy on nausea, vomiting and state of well being. The aim of this study was to evaluate the effect of postoperative administration of IV dextrose on PONV in patients undergoing Laparoscopic Cholecystectomy. Materials & Methods: 150 ASA I OR II patients undergoing laparoscopic surgery were randomly allocated to Group 1 (N=75) to receive one litre of 5% dextrose or Group 2 (N=75) to receive one litre of Ringer Lactate (RL) over a period of 30-40 min after surgery in PACU. All episodes of PONV (nausea, vomiting, retching) for 0-6 hours and 6-24 hours were recorded. Blood glucose was measured before and after completion of study fluid infusion. Requirement of rescue antiemetic therapy, postoperative pain, state of well being and length of stay in PACU were also evaluated as secondary objectives. Results: The incidence of nausea in Group 1 and 2 was (30.3% Vs 57.6%, p=0.041) at 0-6 hrs,(12.5% Vs 18.6%, p=0.364) at 6-24 hours and (42.8% Vs 72.8%, p<0.001) at 0-24 h. The incidence of vomiting was 10.7% Vs 11.8%, 3.5% Vs 5% and 14.2% Vs 16.9% at 0-6h, 6-24h and 0-24h in Group 1 and 2 respectively. Complete response and requirement of rescue antiemetic were comparable in both the groups. Requirement of analgesics were higher in group II as compared to group I between 0-24 h (p=0.042). Incidence of fatigue and hunger were significantly higher in group II as compared to group I. Conclusion: Postoperative administration of iv dextrose reduced the incidence and severity of nausea during the first 24 postoperative hours. It resulted in lesser requirement of rescue analgesics,lesser hunger and fatigue but more thirst postoperatively

Rolapitant improves quality of life of patients receiving highly or moderately emetogenic chemotherapy

PurposeAddition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE).MethodsIn three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18–126]). We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies.ResultsIn the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p < 0.001), nausea score (55.3 vs 53.5, p < 0.05), and vomiting score (59.2 vs 55.8, p < 0.001) versus control; similar results were observed in the MEC/AC study for FLIE total score (112.7 vs 108.6, p < 0.001), nausea score (54.1 vs 52.3, p < 0.05), and vomiting score (58.6 vs 56.3, p < 0.001). A higher proportion of patients reported no impact on daily life with rolapitant than with control in the MEC/AC study (73.2 vs 67.4, p = 0.027).ConclusionsCompared with control, rolapitant improved quality of life in patients receiving HEC or MEC.

Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting Associated with Chemotherapy.

Intravenous fosaprepitant dimeglumine (Emend(®) for injection, IVEmend(®); henceforth referred to as fosaprepitant) is a prodrug of and is rapidly converted to the antiemetic aprepitant, and is approved in several countries worldwide (as part of an antiemetic regimen) for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy (HEC and MEC). This narrative review discusses the pharmacological properties of intravenous fosaprepitant and its clinical efficacy and tolerability in the prevention of nausea and vomiting associated with HEC and MEC. In large, randomized phase III clinical trials, a single intravenous dose of fosaprepitant 150mg was an effective and generally well tolerated addition to an antiemetic regimen that included dexamethasone and a serotonin 5-HT3 receptor antagonist in adult cancer patients undergoing treatment with HEC or MEC. It was also noninferior to an oral aprepitant-based regimen in adult cancer patients undergoing HEC treatment. The tolerability profile of a fosaprepitant-based regimen was typical of that in patients receiving emetogenic chemotherapy, and adverse events were generally consistent with those observed with an aprepitant-based regimen. Fosaprepitant provides a useful addition to antiemetic therapy regimens.