Control Of Vomiting Research Articles

Comparison of granisetron and palonosetron in triplet anti-emetic prophylaxis in non-small cell lung cancer patients receiving cisplatin-based highly emetogenic chemotherapy.

We compared the efficacy of first-generation granisetron and second-generation palonosetron in triplet anti-emetic prophylaxis in patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based high emetogenic chemotherapy (HEC). This prospective, multicenter, non-randomized, observational study was conducted between June 2018 and December 2021. Patients diagnosed with NSCLC who received triplet anti-emetic prophylactic treatment with aprepitant and dexamethasone plus granisetron or palonosetron before the first cycle of chemotherapy were included in the study. At the end of the first week after chemotherapy, the emesis scale was applied to the patients during the outpatient control. The primary endpoint was complete response (CR) and total control (TC). One hundred twenty-one patients were included in the study. Sixty-one patients were in the granisetron group and 60 patients were in the palonosetron group. CR was higher with granisetron in the acute phase (70.5% vs. 58.3%, p = 0.16; respectively) and higher with palonosetron in the delayed phase (61.7% vs. 55.7%, p = 0.5; respectively), although not statistically significant. The TC rates were also not significantly different between the groups (54.1% vs.57.6%, p = 0.69). There was no significant difference between granisetron and palonosetron in both acute and delayed control of emesis in NSCLC patients receiving cisplatin-based HEC.

Exploring the role of ghrelin and des-acyl ghrelin in chemotherapy-induced nausea and vomiting

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 μg/day), DAG (0.2, 1.0, and 5.0 μg/day), or saline (14 μL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg). At the end, the anti-apoptotic potentials of ghrelin and DAG were assessed by measuring Bax expression and cytochrome C activity. Neurotransmitter changes in the brain were evaluated using liquid chromatography–mass spectrometry analysis. Ghrelin and DAG reduced cisplatin-induced emesis in the delayed (24–72 h) but not the acute phase (0–24 h) of emesis. Ghrelin also partially reversed the inhibitory effects of cisplatin on food intake without affecting gastrointestinal myoelectrical activity or causing hypothermia; however, ghrelin or DAG did not prevent these effects. Ghrelin and DAG could attenuate the cisplatin-induced upregulation of Bax and cytochrome C in the ileum. Cisplatin dysregulated neurotransmitter levels in the frontal cortex, amygdala, thalamus, hypothalamus, and brainstem, and this was partially restored by low doses of ghrelin and DAG. Our findings suggest that ghrelin and DAG exhibit protective effects against cisplatin-induced delayed emesis. The underlying antiemetic mechanism may involve GHSR and/or unspecified pathways that modulate the neurotransmitters involved in emesis control in the brain and an action to attenuate apoptosis in the gastrointestinal tract.

Pharmacotherapy Considerations in Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting

Objectives. Although several guidelines are available aiming for optimal chemotherapy-induced nausea and vomiting (CINV) control, there still remain critical therapeutic challenges: (i) recommendations are mainly drug-based, not protocol-based; (ii) the risk of antiemetics-related interactions is not highlighted; (iii) the emetogenicity of a regimen may vary over the cycle; and (iv) the impact of the underlying malignancy is overlooked. Apparently, the existing approach seems not to be generally efficient and puts patients at risk of insufficient use of antiemetics as well as poor emesis control. Evidence Acquisition. This study has re-evaluated the emetogenicity of chemotherapy regimens based on administered medications on each day, drug-drug interactions, combination therapy, and delayed CINV. Results. A literature review was done to re-evaluate the emetogenicity of the commonly accepted chemotherapy regimens based on administered medications on each day, drug interactions, combination therapy, and delayed CINV. Conclusion. The revised CINV prophylaxis protocols with sorted recommendations for hematologic malignancies and solid tumors have been represented, with respect to the availability of prophylactic medications.

Screening study of anti-emetics to improve GDF15-induced malaise and anorexia: Implications for emesis control

Considerable preclinical and clinical attention has focused on the food intake and body weight suppressive effects of growth differentiation factor 15 (GDF15) and its elevated blood levels as a consequence of disease states and disease treatment therapeutics. We have previously reported that exogenous administration of GDF15 induces anorexia through nausea and emesis in multiple species. Importantly, GDF15 signaling as a meditator of chemotherapy-induced anorexia and emesis has recently been demonstrated in both murine and nonhuman primate models. The mechanism, however, by which GDF15 induces malaise and the utility of existing therapeutic targets to counteract its effects remain largely unknown. Using a dose of GDF15 that mimics stimulated levels following chemotherapy administration and reliably induces malaise, we sought to screen anti-emetics that represent distinct pharmacotherapeutic classes hypothesized to reduce GDF15-induced effects in rats. Strikingly, our results showed that none of the tested compounds were effective at preventing GDF15-induced malaise. These results illustrate the complexity of GDF15 signaling mechanism and may have important implications for medical conditions characterized by elevated GDF15 levels and incomplete symptom control, such as chemotherapy-induced nausea and vomiting.

Evaluation of contemporary olanzapine- and netupitant/palonosetron-containing antiemetic regimens for chemotherapy-induced nausea and vomiting.

This post-hoc analysis retrospectively assessed data from two recent studies of antiemetic regimens for chemotherapy-induced nausea and vomiting (CINV). The primary objective was to compare olanzapine-based versus netupitant/palonosetron (NEPA)-based regimens in terms of controlling CINV during cycle 1 of doxorubicin/cyclophosphamide (AC) chemotherapy; secondary objectives were to assess quality of life (QOL) and emesis outcomes over four cycles of AC. This study included 120 Chinese patients with early-stage breast cancer who were receiving AC; 60 patients received the olanzapine-based antiemetic regimen, whereas 60 patients received the NEPA-based antiemetic regimen. The olanzapine-based regimen comprised aprepitant, ondansetron, dexamethasone, and olanzapine; the NEPA-based regimen comprised NEPA and dexamethasone. Patient outcomes were compared in terms of emesis control and QOL. During cycle 1 of AC, the olanzapine group exhibited a higher rate of 'no use of rescue therapy' in the acute phase (olanzapine vs NEPA: 96.7% vs 85.0%, P=0.0225). No parameters differed between groups in the delayed phase. The olanzapine group had significantly higher rates of 'no use of rescue therapy' (91.7% vs 76.7%, P=0.0244) and 'no significant nausea' (91.7% vs 78.3%, P=0.0408) in the overall phase. There were no differences in QOL between groups. Multiple cycle assessment revealed that the NEPA group had higher rates of total control in the acute phase (cycles 2 and 4) and the overall phase (cycles 3 and 4). These results do not conclusively support the superiority of either regimen for patients with breast cancer who are receiving AC.

Pharmacokinetics of maropitant citrate in Rhode Island Red chickens (Gallus gallus domesticus) following subcutaneous administration.

Maropitant citrate is a synthetic neurokinin‐1 receptor antagonist and substance P inhibitor used for control of emesis in dogs in cats. Maropitant citrate is used empirically in birds, despite a lack of pharmacokinetic data in avian species. The objective of this study was to determine the pharmacokinetic profile of a single dose of maropitant citrate 1 and 2 mg/kg subcutaneously (SC) in eight Rhode Island Red hens (Gallus gallus domesticus). A crossover study design was used with 1‐week washout between trials. Blood samples were collected over 36 h after drug administration. Plasma concentrations were measured using liquid chromatography–tandem mass spectrometry and pharmacokinetic parameters were determined via non‐compartmental analysis. The mean maximum plasma concentration, time to maximum concentration, and elimination half‐life following 1 and 2 mg/kg SC were 915.6 ± 312.8 ng/ml and 1195.2 ± 320.2 ng/ml, 0.49 ± 0.21 h and 1.6 ± 2.6 h, and 8.47 ± 2.24 h and 8.58 ± 2.6 h, respectively. Pharmacokinetic data suggests doses of 1 or 2 mg/kg SC may be administered every 12–24 h to maintain above target plasma concentration similar to dogs (90 ng/ml). These data provide a basis for further investigation of maropitant citrate pharmacokinetics and pharmacodynamics in birds.

Efficacy of olanzapine, netupitant, and palonosetron in controlling nausea and vomiting associated with highly emetogenic chemotherapy in patients with breast cancer (OLNEPA).

12104 Background: Chemotherapy induced nausea and vomiting (CINV) is a highly prevalent adverse event1,2 that can result in decreased quality of life, dose reduction and interruptions of treatment.3 Four drug protocol including Olanzapine, 5-hydroxytryptamine type 3 receptor (5HT3) antagonist, a neurokinin 1 receptor (NK1) antagonist and dexamethasone is the current standard of care for highly emetogenic chemotherapy (HEC) 2,4-6. Corticosteroids are associated with side effects like insomnia and weight gain. To our knowledge, total Dexamethasone omission has not been addressed previously. Methods: This is a prospective single arm phase II study designed to evaluate the efficacy of Olanzapine, Netupitant and Palonosetron in controlling nausea and vomiting induced by highly emetogenic chemotherapy. Eligible patients were women with histologic confirmed breast cancer, planned to start treatment with Doxorubicin and Cyclophosphamide. Exclusion criteria included use of opioids or antipsychotic medications, medical condition that could potentially cause vomiting or inability to take oral medications. Patients were assigned to take Olanzapine 5mg QD, days 1 – 5, Netupitant 300mg and Palonosetron 0.5mg on day one. No corticosteroid use was allowed. The null hypothesis considered that the scheme containing Olanzapine, Netupitant and Palonosetron could not effectively control nausea. Based on a previous phase III study with Olanzapine (Navari et al.), we set the control of nausea at 20% and the expected control rate at 40% for the present study. To reach 5% (two-sided) significance and 80% statistical power, we calculated that a minimum sample size of 50 patients was required, assuming a 5% dropout rate. We used the one-sample T-test of proportion to analyze the data, based on intent-to-treat (ITT) The primary endpoint was complete control of nausea in the first 5 days after chemotherapy administration. Secondary endpoints were complete emesis control (no emesis, no use of rescue medication) and complete control (no emesis, no rescue and no nausea) Results: Fifty patients were enrolled from January 2020 to December 2021. The median age was 47.6 years-old (range: 29 – 78 years) and 48 patients (96%) received chemotherapy with curative intent. For the primary endpoint, complete nausea control rate was 46% (IC 32 – 59%) and p < 0.0001. The emesis control rate was 68% (IC 55 – 80%) and overall control rate was 46% (IC 32 – 59%). One patient dropped out for dizziness and drowsiness following administration of Olanzapine. Conclusions: Omitting Dexamethasone for highly emetogenic chemotherapy is feasible and showed similar control of nausea and vomiting compared to standard four-drug protocol. This could be a potential prophylactic regimen of choice for patients who have a contraindication for Dexamethasone use. Clinical trial information: NCT04669132.

Postoperative pain management in gynecologic oncology: regional anesthesia effects on time to pain control and achieving postoperative milestones

<h3>Objectives:</h3> We investigated the time to achieve postoperative milestones in patients who underwent exploratory laparotomy for suspected gynecologic malignancy and received either patient-controlled analgesia alone (PCA), PCA with transversus abdominus plane block (TAP), or PCA with continuous epidural infusion (CEI). <h3>Methods:</h3> A retrospective cohort study of patients who underwent open gynecologic oncology surgery in a university was conducted over 18 months. Our primary outcomes included time to achieve the following postoperative milestones: pain control (mean pain score ≤ 5), foley catheter removal, ambulation, flatus, tolerating a regular diet, and control of nausea and emesis. All milestones, except for foley catheter removal, were measured using postoperative day (POD). Foley catheter removal was measured in hours after insertion and analyzed as a categorical variable using quartiles. All postoperative milestones were compared using Fisher's Exact Test. <h3>Results:</h3> Of 214 eligible patients, 127 received PCA alone, 76 received additional TAP block, and 11 received additional CEI. 19 patients without PCA or regional, and 13 patients without PCA, were excluded. Pain control took longer in the CEI group as over half of those who received PCA alone (54%) or TAP (57%) achieved pain control on POD 0 compared to 30% in CEI (p=0.02). Similarly, by POD 3, only 80% of the CEI group had pain controlled compared to 96% in PCA and 85% in TAP (p=0.02). CEI also lagged in time to foley removal as none (0%) of the CEI group had foley removal within the first quartile, 0-15 hours, whereas 23% of the PCA group and 27% of the TAP group had achieved successful removal by that time (p=0.02). This trend continued with 73%, 28%, and 20% of the CEI, PCA, and TAP groups, respectively had foley removal within the last quartile, 41-503 hours (p=0.02). The CEI group also took longer to ambulate with 18% ambulating by POD 1 compared to 59% in PCA and 64% in TAP (p=0.01). Similarly, by POD 2, only 54% of the CEI patients were ambulating compared to 89% in PCA and 90% in TAP (p=0.01). The CEI group lagged in time to regular diet, as only 9% were eating by POD 1 vs 35% in PCA and 29% in TAP, although this finding was not statistically significant (p=0.07). The CEI group also experienced increased time to flatus with 9% on POD 1 compared to 17% in PCA and 7% in TAP (p=0.02). Only 9% of the CEI patients had nausea controlled by POD 1, whereas 48% in PCA and 49% in TAP groups met that milestone by then (p=0.02). It took 3 or more postoperative days for 82% of the CEI group to have controlled nausea. When reviewing these results in the combined regional group (TAP and CEI) vs PCA alone, there were no statistically significant differences except in time to flatus, with 17% of the PCA group passing flatus by POD 1 compared to 7% in the regional group (p=0.03). <h3>Conclusions:</h3> Our study showed that regional anesthesia increased time to flatus in patients who underwent open gynecologic surgery. Although limited by small sample size, CEI was an outlier in time to postoperative milestones, including pain control, ambulation, control of nausea and emesis, and foley removal. Benefits and drawbacks of CEI anesthesia should be considered using full assessment of the effect on postoperative milestones. Further study of costs of CEI vs TAP anesthesia, while not in the scope of this study, can provide further context for decision making. Our results merit future investigation into the effects of regional anesthesia, especially epidural, on time to postoperative milestones.

Perioperative Fluid Management as a Component of Early Recovery after Surgery (ERAS) Protocols for Pediatric Patients

Sentinel studies by Bartram and Kehlet challenged the acceptance of the inevitable consequences of the adverse physiologic effects of the stress response to surgery. This led to the evolution of Enhanced Recovery after Surgery (ERAS) protocols. ERAS is a multi-disciplinary approach aimed at improving care of the surgical patient? ERAS protocols/pathways were developed by the application of sound scientific knowledge to perioperative care. ERAS protocols have been shown to reduce postoperative complications, reduce hospital length of stay, and reduce costs. Although some ERAS protocols are highly specific to the type of surgery, issues common to most of the protocols are pain management, perioperative nutrition, control of nausea and emesis, antimicrobial therapy, thromboembolism prophylaxis, and precise perioperative fluid administration. Protocols often introduce multiple changes to clinical practice simultaneously and, if a positive effect is found, it is difficult to determine the contribution of each component.

Addition of aprepitant improves acute emesis control in children and adolescents receiving induction chemotherapy for acute myeloid leukaemia: a randomised, open-label trial

ObjectivesMore than 50% patients develop emesis during induction therapy for acute myeloid leukaemia (AML). The addition of aprepitant for emesis control in children receiving induction for AML have not been...

Efficacy and Safety of Aprepitant for the Prevention of Nausea and Emesis During Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC): A Phase 2 Trial

Few studies reported effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This prospective phase II study was performed to assess the safety and efficacy of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant in LA-HNSCC patients receiving CCRT with high-dose cisplatin. Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concurrent cisplatin 100 mg/m2 in 6.5 weeks. Cisplatin was divided into 3 days on day 1-3 every 3 weeks, in company with the antiemesis regimen. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR) in the overall phase, defined as no emesis and no use of rescue therapy in this period. Rescue medication was permitted for ≥ grade 2 nausea and emesis. Per the Simon two-stage design, 17 patients are enrolled in stage 1; if ≥ 13 patients are CR, 26 additional patients are enrolled in stage 2. If CR rate is ≥ 80%, the trial is deemed positive. The study was registered with ClinicalTrials.gov, number NCT03572829. Between Jan 2018 and Jan 2020, 44 LA-HNSCC patients were enrolled. The median age was 53 years old (range, 18-66), and 86.4% were male. All patients fulfilled the radiotherapy and the first cycle of cisplatin. Cisplatin dose changes were reported in 11 (28.9%) of 38 patients during the second cycle, while other 6 patients terminated chemotherapy owing to the hematotoxicities and hepatotoxicities. Sixteen of 17 patients were CR in stage 1 and 27 patients were enrolled in stage 2. The overall CR rates was 88.6% (39/44). The CR rates in cycles 1 and 2 were 90.9% (40/44) and 92.1% (35/38), respectively. The overall rates of no emesis and no nausea were 88.6% (39/44) and 61.4% (27/44). Grade 2 emesis occurred in 3 patients (1 patient was rescued) and grade 1 in 2 patients. The median score of nausea was 4 (range, 1-10). The rates of no emesis in cycle 1 and 2 were 90.9% and 92.1%, respectively. The corresponding rates of no nausea were 61.4% and 78.9%, respectively. There was no ≥ grade 3 antiemesis treatment related adverse event. The major toxicities were constipation (17 patients, 38.6%) and hiccough (7 patients, 15.9%). Aprepitant in addition to ondansetron and dexamethasone significantly improve control of emesis and nausea in patients with LA-HNSCC receiving concomitant high-dose cisplatin and radiotherapy. Randomized phase 3 studies are necessary to further define the potential role of NK1-RA in this setting.

1814MO Addition of aprepitant improves acute emesis control in children and adolescents receiving induction chemotherapy for acute myeloid leukaemia: A randomized, open-label trial

1814MO Addition of aprepitant improves acute emesis control in children and adolescents receiving induction chemotherapy for acute myeloid leukaemia: A randomized, open-label trial

Revisiting the physiology of nausea and vomiting-challenging the paradigm.

The predominant neurotransmitters and receptors for acute and delayed chemotherapy-induced nausea and vomiting (CINV) are represented in the current paradigm, which reflects successful control of emesis. However, control of nausea (N) lags behind management of vomiting (V). This review aims to re-examine and incorporate new information about the mechanisms of V and N. The initial literature search focused on CINV. Keywords in articles led to subsequent discovery of publications focused on N&V in other medical and scientific fields (e.g., gastroenterology, neurology, cannabinoid science, neuropharmacology, and motion sickness). Using keywords to identify other sources continued until no further recent, meaningful publications were found. More than 86% of references were from recent non-oncology journals and books, suggesting there are many areas for cross-fertilization research into mechanisms and management of N&V-particularly of N, which involves overlapping and dissimilar CNS areas from V. Information from cited articles was incorporated into visual representation of N&V, which is certainly not exhaustive but supports highly complex processes in the stomach and gut, the vagus nerve and spinal cord neurons, the nucleus tractus solitarii, and the anterior insular cortex and anterior cingulate cortex with input from the amygdala. These data support the idea that mechanisms for N, whatever the cause, must be highly similar. Continued research into nausea, including patient-reported evaluation and outcomes, is important; interventions for nausea could be considered adjuvants to current standard of care antiemetics and be individualized, depending on patient-reported efficacy and adverse effects and preferences.

Evaluation of the Use of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients.

A neurokinin-1 (NK1) receptor antagonist is recommended with a 5-HT3 receptor antagonist and dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving highly emetogenic chemotherapy. Data for fosaprepitant use in pediatric patients is lacking. A retrospective chart review was conducted using an electronic medical record to characterize the use of fosaprepitant in patients aged 10 months to 18 years at a single institution from August 2015 to January 2017. Thirty-nine patients received fosaprepitant 4 mg/kg (maximum, 150 mg) for prevention of CINV, and 35 were included in the analysis. Ten patients 5 years of age or older who received fosaprepitant after October 2016 were eligible for a follow-up phone call to assess control of delayed CINV. Complete control of emesis was observed in 89% of patients during the acute phase, 63% during the delayed phase, and 60% overall. Overall incidence of nausea as documented in the medical record was 43%. Among the 10 patients who completed follow-up phone calls, 30% experienced emesis and 50% experienced nausea after discharge. Fosaprepitant may be safe and effective in the prevention of CINV in pediatric patients as young as 10 months of age.

Revised antiemetics guidelines and the impact on nutritional status during induction chemotherapy in children with high‐risk neuroblastoma

High-risk neuroblastoma (HR NBL) treatment requires intensive induction chemotherapy. The profoundly emetogenic agents used can compromise nutritional status. Our institution introduced a new antiemetic guideline in 2010 incorporating regular dexamethasone, in addition to ondansetron, for all highly emetogenic protocols. A retrospective comparative review of pediatric patients diagnosed with HR NBL who received rapid COJEC induction chemotherapy as per HR-SIOPEN NBL trial. Prophylactic antiemetics were prescribed regardless of chemotherapy emetogenicity in group A (2004-2010) but for defined time periods considering chemotherapy emetogenicity in group B (2010-2017). Sixty-three children were eligible for inclusion (median age, 31 months; range, 1-88 months). Group A had more episodes of emesis than group B (189 vs. 116, P<0.0001). There was a significant difference in weight-for-age Z score change between the groups by induction end (P=0.0027). Four children (13%) in group A lost >10% body weight versus none in group B. Nutrition support (NS) was utilized by 29 children (94%) in group A and 22 children (69%) in group B. Group A had a median of 3 (range, 1-7) admissions for febrile neutropenia (FN) versus a median of 1.5 (range, 0-4) for group B (P=0.003) during induction. The review of our guidelines led to reduced emesis frequency for group B. They also required less NS, followed expected growth trajectories more closely and had fewer FN admissions. We propose that this may have occurred due to better emesis control resulting in improved nutritional status and associated enhanced immune function.

Mo1560 - Central GLP-1 Receptors are Differentially Involved in Emesis and Feeding Control in Suncus Murinus (House Musk Shrew)

Mo1560 - Central GLP-1 Receptors are Differentially Involved in Emesis and Feeding Control in Suncus Murinus (House Musk Shrew)

Efficacy and Safety of Aprepitant in Combination with Dexamethasone, Granisetron and Metoclopramide as a Prophylaxis of Chemotherapy-Induced Nausea and Vomiting in a Acute and Delayed Emesis in Arab Cancer Patient

Background: Chemotherapy Induced Nausea and Vomiting (CINV) is one of the greatest sources of distress for patients. Severe CINV may force interruption of chemotherapy, it is important to control CINV to achieve successful chemotherapy. Objective: This study to evaluate the efficacy and safety of aprepitant in a regimen containing aprepitant in combination with dexamethasone, granisetron and metoclopramide (APRDGM) versus a regimen dexamethasone, granisetron and metoclopramide (DGM) only, as a prophylaxis in (CINV) in highly emetogenic chemotherapy(HEC) in Arabic cancer patients. Setting: This study was conducted at King Abdul-Aziz Medical city (Eastern Region, AlHasa, Saudi Arabia). Methods: 309 patients all Arab population, treated with HEC, were enrolled in a retrospective, cohort study to investigate the efficacy and safety of (APR-DGM) compared to (DGM) regimen. Main outcome measure: The primary efficacy endpoint was the complete response (CR) for acute emesis and determines the adverse drug events. Secondary endpoint was the CR for delayed emesis. Results: The APR-DGM regimen showed a significantly improved control in the management of CINV in patients treated with HEC in acute emesis compared to the DGM regimen (P=0.0021). No significant difference was observed between the two regimens regards to delayed emesis (P=0.145). Both regimens were well tolerated, and the rates of adverse events were not significantly different between the regimens. Conclusion: The addition of aprepitant to the standard regimen of dexamethasone, granisetron and metoclopramide was found to be significantly better than dexamethasone, granisetron and metoclopramide alone, but only in the control of acute emesis, with no significant change in delayed emesis in Arab population.

Direct modification of the 5-HT3 receptor current by some anticancer drugs

The serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor is an important target in the control of emesis, and 5-HT3 receptor antagonists are effective against the early phase chemotherapy evoked vomiting. We recently reported that the anticancer drugs irinotecan and topotecan directly modulate the 5-HT-mediated 5-HT3 receptor current in vitro. In addition, the drug response depends on the 5-HT3 subunit composition. Here, we explored the effects of 35 anticancer drugs on the 5-HT3 receptor current. We microinjected Xenopus laevis oocytes with human 5-HT3A cRNA or a combination of human 5-HT3A and human 5-HT3B cRNA, and performed two-electrode voltage clamp recordings of 5-HT3A and 5-HT3AB receptor currents in the presence of each of the 35 drugs. Over 25% of the drugs we tested inhibited or potentiated the 5-HT3 receptor current. The drugs that modulated the 5-HT3 receptor current had molecular weights of approximately 500. These results implied that these anticancer drugs could affect 5-HT3 receptor.

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew).

Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control.

Medication-related issues associated with adherence to long-term tyrosine kinase inhibitors for controlling chronic myeloid leukemia: a qualitative study.

PurposePoor adherence to tyrosine kinase inhibitors (TKIs) could compromise the control of chronic myeloid leukemia (CML) and contributes to poorer survival. Little is known about how medication-related issues affect CML patients’ adherence to TKI therapy in Malaysia. This qualitative study aimed to explore these issues.Patients and methodsIndividual face-to-face, semistructured interviews were conducted at the hematology outpatient clinics of two medical centers in Malaysia from August 2015 to January 2016. CML patients aged ≥18 years who were prescribed a TKI were invited to participate in the study. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed.ResultsFour themes were identified from 18 interviews: 1) concerns about adverse reactions to TKIs, 2) personal beliefs regarding the use of TKIs, 3) mismanagement of TKIs in daily lives, and 4) financial burden in accessing treatment. Participants skipped their TKIs due to ineffective emesis control measures and perceived wastage of medication from vomiting. Participants also modified their TKI therapy due to fear of potential harm from long-term use, and stopped taking their TKIs based on belief in curative claims of traditional medicines and misconception about therapeutic effects of TKIs. Difficulty in integrating the dosing requirements of TKIs into daily lives led to unintentional skipping of doses, as well as the risk of toxicities from inappropriate dosing intervals or food interactions. Furthermore, financial constraints also resulted in delayed initiation of TKIs, missed clinic appointments, and treatment interruptions.ConclusionMalaysian CML patients encountered a range of medication-related issues leading to a complex pattern of nonadherence to TKI therapy. Further studies should investigate whether regular contact with patients to improve understanding of treatment rationale, to elicit and address patients’ concerns about adverse reactions, and to empower patients with skills to self-manage their medications might promote better adherence to TKIs and improve CML patients’ outcome.