Chemotherapy-induced nausea and vomiting control in pediatric patients receiving ifosfamide plus etoposide: a prospective, observational study.

PURPOSE: Little evidence exists regarding the emetogenicity of chemotherapy in pediatric patients. This study describes the prevalence of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving etoposide plus ifosfamide over 5 days, a common pediatric regimen. METHODS: English-speaking, non-chemotherapy-naïve patients aged 4 to 18 years about to receive etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day over 5 days participated. Antiemetic prophylaxis was determined by each patient's care team. Emetic episodes were recorded and nausea severity was assessed by patients beginning with the first chemotherapy dose, continuing until 24 h after the last chemotherapy dose (acute phase) and ending 7 days later (delayed phase). The proportion of patients experiencing complete acute CINV control (no nausea, no vomiting, and no retching), the primary study endpoint, was described. The prevalence of complete chemotherapy-induced vomiting (CIV) and chemotherapy-induced nausea (CIN) during the acute, delayed, and overall (acute plus delayed) phases; complete delayed and overall CINV control; and anticipatory CINV were also determined. RESULTS: Twenty-four patients participated; acute CINV was evaluable in 22. Most (75%; 18/24) received a 5-HT3 antagonist plus dexamethasone for antiemetic prophylaxis. Few (23%; 5/22) experienced complete acute CINV control. Complete acute CIV and CIN control were experienced by 57% (13/23) and 27% (6/22) of patients, respectively. Complete delayed CINV, CIV, and CIN control rates were 42% (8/19), 70% (14/20), and 42% (8/19), respectively. CONCLUSIONS: Our findings support the classification of etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day IV over 5 days as highly emetogenic. This information will optimize antiemetic prophylaxis selection and CINV control in pediatric patients.

Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline.

This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single-agent and 13 combination-agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.

Nausea and vomiting in children and adolescents receiving intrathecal methotrexate: A prospective, observational study.

BACKGROUND: The prevalence of nausea and vomiting after receipt of intrathecal methotrexate (IT-MTX) in pediatric oncology patients is unknown. METHODS: Patients (4-18 years) about to receive IT-MTX were eligible to participate in this prospective, observational study. Patients received antiemetics as prescribed by their clinical team. Nausea severity (patient-assessed), timing of emetic episodes, and administration of antiemetics were recorded beginning immediately prior to IT-MTX administration, for the next 24 hr (acute phase), and for a maximum of 7 additional days (delayed phase). Complete chemotherapy-induced nausea and vomiting (CINV) control was defined as no emetic episodes and no nausea. RESULTS: One hundred patients consented to participate in this study; 70 provided evaluable data (mean age: 8.3 years; range: 4.1-17.6). Most (94%) received propofol-containing anesthesia for IT-MTX administration. Most (89%) received a 5-HT3 antagonist prior to IT-MTX. During the acute phase, 36 children (51%) experienced complete CINV control, 67 (96%) complete vomiting control, and 36 (51%) complete nausea control. Severe acute phase nausea was reported by 12 children (17%). During the delayed phase, 35 patients (50%) experienced complete CINV control, 60 (86%) complete vomiting control, and 36 (51%) complete nausea control. Severe nausea was reported in the delayed phase by 27 (39%) patients. CONCLUSIONS: Most pediatric patients who received IT-MTX and prophylaxis with ondansetron or granisetron experienced complete acute and delayed vomiting control. However, nausea control was poor and severe nausea was reported by many children. Effective interventions to control nausea are needed.

Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: A focused update.

This update of the 2013 clinical practice guideline provides clinicians with guidance regarding the use of aprepitant and palonosetron for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) in children. The recommendations were based on three systematic reviews. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT3 antagonists recommended for children receiving highly emetogenic chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of age or older receiving HEC. To optimize CINV control in children, future work must focus on closing critical research gaps.

Guideline for the Treatment of Breakthrough and the Prevention of Refractory Chemotherapy-Induced Nausea and Vomiting in Children With Cancer.

This clinical practice guideline provides an approach to the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) and the prevention of refractory CINV in children. It was developed by an international, interprofessional panel and is based on systematic literature reviews. Evidence-based interventions for the treatment of breakthrough and prophylaxis of refractory CINV are recommended. Gaps in the evidence used to support the recommendations made in this clinical practice guideline were identified. The contribution of these recommendations to breakthrough and refractory CINV control in children requires prospective evaluation.

Poor chemotherapy-induced nausea and vomiting control in children receiving intermediate or high dose methotrexate.

PURPOSE: Chemotherapy emetogenicity is the most important known determinant of chemotherapy-induced vomiting (CIV) in children. However, direct evidence regarding the emetogenic potential of chemotherapeutic agents in children is limited. This study describes the prevalence of complete control of acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in children receiving methotrexate. The prevalence of anticipatory CINV is described, and risk factors for CINV are explored. METHODS: English-speaking children (4 to 18 years) receiving intermediate-dose (ID-MTX: >1 to <12 g/m(2)/dose) or high-dose methotrexate (HD-MTX: ≥12 g/m(2)/dose) participated in this prospective study. Emetic episodes, nausea severity, and antiemetic administration were documented for 24 h from the start of the methotrexate infusion (acute phase) and for up to a further 168 h (delayed phase). CINV prophylaxis was provided at the discretion of the treating physician. Anticipatory CINV was assessed in the 24 h preceding chemotherapy. Complete CINV control was defined as no emetic episodes and no nausea. RESULTS: Thirty children (mean age, 11.8 ± 4 years; ID-MTX, 20; HD-MTX, 10) completed the study. CINV prophylaxis included the following: ondansetron/granisetron plus dexamethasone or nabilone. Few patients experienced complete CINV control (ID-MTX: acute phase 20%, delayed phase 5%; HD-MTX: acute phase 0%, delayed phase 30%). Complete emesis control was higher (ID-MTX: acute phase 70%, delayed phase 50%; HD-MTX: acute phase 70%, delayed phase 60%). Anticipatory CINV was reported by 6/28 patients (21%). Patient age, sex, and history of motion sickness were not significant predictors of CINV. CONCLUSIONS: The poor complete CINV control rate in children receiving methotrexate confirms the classification of HD-MTX as highly emetogenic chemotherapy (HEC) and suggests that ID-MTX be reclassified as HEC.

Olanzapine for treatment and prevention of acute chemotherapy-induced vomiting in children: a retrospective, multi-center review.

BACKGROUND: This retrospective review provides preliminary data regarding the safety and efficacy of olanzapine for chemotherapy-induced vomiting (CIV) control in children. PROCEDURE: Children <18 years old who received olanzapine for acute chemotherapy-induced nausea and vomiting (CINV) control from December 2010 to August 2013 at four institutions were identified. Patient characteristics, chemotherapy, antiemetic prophylaxis, olanzapine dosing, CIV control, liver function test results and adverse events were abstracted from the health record. Toxicity was graded using CTCAEv4.03. RESULTS: Sixty children (median age 13.2 years; range: 3.10-17.96) received olanzapine during 158 chemotherapy blocks. Olanzapine was most often (59%) initiated due to a history of poorly controlled CINV. The mean initial olanzapine dose was 0.1 mg/kg/dose (range: 0.026-0.256). Most children who received olanzapine beginning on the first day of the chemotherapy block experienced complete CIV control throughout the acute phase (83/128; 65%). There was no association between the olanzapine dose/kg and complete CIV control (OR 1.01; 95% CI: 0.999-1.020; P = 0.091). Sedation was reported in 7% of chemotherapy blocks and was significantly associated with increasing olanzapine dose (OR: 1.17; 95% CI: 1.08-1.27; P = 0.0001). Of the 25 chemotherapy blocks where ALT and/or AST were reported more than once, grade 1-3 elevations were observed in five. The mean weight change in 31 children who received olanzapine during more than one chemotherapy block was 0% (range: -22 to +18). CONCLUSION: Olanzapine may be an important option to improve CIV control in children. Prospective controlled evaluation of olanzapine for CINV prophylaxis in children is warranted.

Mapping Course Assessments to Canadian Pharmacy Educational Outcomes to Ensure Pharmacy Students' Practice Readiness.

Objective. The entry-to-practice PharmD degree is designed to meet the Educational Outcomes of the Association of Faculties of Pharmacy of Canada (AFPC). We set out to evaluate how assessment strategies in a "capstone" course align with AFPC educational outcomes, their respective key and enabling competencies, and whether enough assessments exist for students to demonstrate achievement of competencies prior to embarking on advanced pharmacy practice experiences.Methods. We mapped each assessment's objectives, content, and methods to the key and enabling competencies of each role of a pharmacist. The number of enabling competencies mapped represents the extent to which the assessment addressed the associated key competency and broader role. Deidentified student performance data were analyzed to identify achievement of competencies despite failed assessments.Results. Of the seven role descriptions, the roles care provider, communicator, and collaborator were the most comprehensively assessed. The roles leader-manager and health advocate were assessed to a limited extent. The role scholar was not covered to a great depth across assessments. The role professional was not represented in most assessments except for the final examination. Students with failed assessments generally had ample opportunity to demonstrate competencies through other assessments.Conclusion. Mapping assessments to AFPC educational outcomes is an essential step to demonstrate direct evidence that students have achieved the intended learning outcomes. Our map revealed that the assessments sufficiently overlapped with most AFPC educational outcomes with a few exceptions. It is important to create multiple opportunities within a course for students to demonstrate achievement of competencies to ensure practice readiness.

The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis.

INTRODUCTION: Metoclopramide is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV) and for CINV prophylaxis in children. The drug regulatory agencies of Canada and the EU have revised the labelling of metoclopramide to contraindicate its use in children aged <1 year and to caution against its use in children aged <5 years and its duration of use beyond 5 days. OBJECTIVE: This review describes the safety of metoclopramide in children when given for any indication. METHODS: We conducted electronic searches in MEDLINE and Embase as of 9 March 2015. All studies in English reporting adverse effects associated with the use of metoclopramide in children (aged ≤18 years) were included. Adverse effects that had a cumulative incidence of at least 1 % and were reported in prospective studies were synthesized. RESULTS: A total of 108 (57 prospective) studies involving 2699 patients (2745 metoclopramide courses) were included. The most common adverse effects reported in prospective studies of metoclopramide in children were extrapyramidal symptoms (EPS; 9 %, 95 % confidence interval [CI] 5-17), diarrhea (6 %, 95 % CI 4-9), and sedation (multiple-dose studies: 6 %, 95 % CI 3-12). Dysrhythmia, respiratory distress/arrest, neuroleptic malignant syndrome, and tardive dyskinesia were rarely associated with metoclopramide use. LIMITATIONS: The definitions of adverse effects reported in the included studies were heterogeneous, and the risk of bias in most studies was moderate. CONCLUSIONS: The most commonly reported adverse effects associated with the use of metoclopramide in children-EPS, diarrhea, and sedation-were reversible and of no long-term significance. Adverse effects that were life threatening or slow to resolve were rarely associated with its use in children.

The Safety of Prochlorperazine in Children: A Systematic Review and Meta-Analysis.

INTRODUCTION: Prochlorperazine is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV). The objective of this review was to describe its safety in children when given for any indication to help define its role for CINV control in children. METHODS: Electronic searches of MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials were performed as of 9 March 2015. All studies in English reporting adverse effects (AEs) associated with prochlorperazine in children (≤18 years) were included. AEs were synthesized for prospective studies. RESULTS: Forty-nine (15 prospective) studies evaluating the use of prochlorperazine in 758 children were included. The most commonly reported AEs in prospective studies of prochlorperazine in children were sedation (multiple-dose studies: 10 %, 95 % CI 5-21) and extrapyramidal symptoms (EPS) (single-dose studies: 9 %, 95 % CI 3-29; multiple-dose studies: 4 %, 95 % CI 1-11). Serious AEs (seizure, neuroleptic malignant syndrome, autonomic collapse, tardive dyskinesia) were rarely associated with prochlorperazine use in children. Five fatalities were reported in children receiving prochlorperazine. LIMITATIONS: The limitations of this systematic review and meta-analysis were that the AEs reported in the included studies were heterogeneous, the prospective use of systematic clinical tools to identify AEs was rare, and the risk of bias in most prospective studies was moderate. CONCLUSIONS: The most common AEs reported with the pediatric use of prochlorperazine are EPS and sedation. Fatalities, life-threatening, and persistent AEs have also been reported.

Comparative effectiveness research in antineoplastic-induced nausea and vomiting control in children.

Antineoplastic-induced nausea and vomiting (AINV) is one of the most distressing adverse effects experienced by adult and pediatric patients receiving antineoplastic agents. Despite this, evidence of the efficacy and safety of antiemetic interventions in children is limited, and prevention and treatment approaches vary widely between centers. The purpose of this review is: first, to describe the barriers to comparative antiemetic effectiveness research in AINV control in children; second, to highlight limitations of the currently available pediatric AINV evidence; third, to summarize and discuss comparative effectiveness research specific to AINV control in children, with a focus on agents recommended in evidence-based guidelines developed for acute phase AINV control; and finally, to offer guidance regarding future comparative effectiveness research in this field.

The safety of olanzapine in young children: a systematic review and meta-analysis.

BACKGROUND: Olanzapine is frequently prescribed in young children for psychiatric conditions. It may be an option for chemotherapy-induced nausea and vomiting (CINV) control in children. The objective of this review was to describe the safety of olanzapine in children less than 13 years of age to determine if safety concerns would be a barrier to its use for CINV prevention. METHODS: Electronic searches were performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus. All studies in English reporting adverse effects associated with olanzapine use in children younger than 13 years or with a mean/median age less than 13 years were included. Adverse outcomes were synthesized for prospective studies. RESULTS: A total of 47 studies (17 prospective) involving 387 children aged 0.6-18 years were included; nine described olanzapine poisonings. Weight gain or sedation were reported in 78 % [95 % confidence interval (CI) 63-95] and 48 % (95 % CI 35-67), respectively. Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9 % (95 % CI 4-21) and 14 % (95 % CI 7-26), respectively. Elevation in liver function tests or blood glucose abnormalities were reported in 7 % (95 % CI 2-20) and 4 % (95 % CI 1-17), respectively. No deaths were attributed to olanzapine. LIMITATIONS: No studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous. CONCLUSIONS: Most adverse events associated with olanzapine use in children less than 13 years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials.