Dinutuximab: An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations for dinutuximab. DATA SOURCES: MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma. Other information was identified from package insert, Biologics License Application, abstracts, news releases, and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: Identified English-language articles were reviewed. Selected studies included phase I through III. DATA SYNTHESIS: High-risk neuroblastoma is primarily a childhood cancer with 5-year survival rates of 40% to 50%. Treatment for high-risk neuroblastoma includes induction chemotherapy, surgery, myeloablative chemotherapy with autologous hematopoietic stem cell transplant, and radiation therapy. For patients achieving clinical remission, limited treatments exist for preventing relapse. Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. In phase III trials, dinutuximab increased 2-year event-free survival and overall survival when compared to standard treatment. Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension. CONCLUSIONS: Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. Ongoing research will determine if dinutuximab could be used earlier in treatment, in nonresponders to initial therapies, in combination with chemotherapy, or in other cancers.

Correlation of a Vancomycin Pharmacokinetic Model and Trough Serum Concentrations in Pediatric Patients.

BACKGROUND: Vancomycin trough concentrations specific to pediatric patients have yet to be validated that achieve an area under the curve (AUC) over 24 hours to minimum inhibitory concentration (MIC) ratio ≥400. The primary objective of this study was to validate a pharmacokinetic model in a pediatric hospital and determine the correlation between a calculated AUC/MIC ratio and measured trough vancomycin concentration. METHODS: A retrospective evaluation of patients aged 3 months to 18 years prescribed vancomycin at a pediatric hospital between January 2012 and June 2013. The correlation between patient-specific AUC/MIC and measured vancomycin trough concentration was assessed. RESULTS: Forty pediatric patients with 40 vancomycin trough concentrations and documented Staphylococcus aureus cultures were included in the study. Median age was 8.5 (interquartile range, 2-14.3) years, median weight 28.7 (range, 14-50.2) kg, and mean baseline serum creatinine 0.51 ± 0.3 mg/dL. The mean daily dose of vancomycin prescribed was 58 ± 13.8 mg/kg/d. The mean vancomycin trough concentration was 11 ± 5.5 mcg/mL, and the mean AUC/MIC was 534 ± 373. No correlation was found between trough concentration and AUC/MIC (r = 0.082, p = 0.07). CONCLUSIONS: This study validates the clinical applicability of a pharmacokinetic model for calculating vancomycin clearance to determine patient-specific AUC over 24 hours in pediatrics. Trough concentrations associated with proposed therapeutic AUC/MIC ratios were lower than reported in the adult population. Further research is needed to determine if AUC/MIC, trough concentration, or both is best for monitoring therapeutic efficacy of vancomycin in pediatrics.

Prevalence of depression and antidepressant therapy use in a pediatric cystic fibrosis population.

BACKGROUND: Depression is associated with significant morbidity and mortality. In recent years reports of depression in cystic fibrosis (CF) patients of all ages have increased. As awareness of depression in CF increases, there remains limited data regarding the prevalence and management of depression in the pediatric CF population. OBJECTIVES: To assess the prevalence of depression, describe depression treatment regimens, and identify risk factors for depression in the pediatric CF population at a single care center. METHODS: A retrospective chart review was conducted on 190 patients at 1 accredited CF center. Patient demographics and clinical characteristics were collected and compared between patients with depression and patients without depression. In addition, the treatment strategies of patients with depression were recorded. RESULTS: The number of patients with a documented diagnosis of depression was found to be 9%, and 50% of these patients were prescribed antidepressant therapy. The most common class of medication prescribed for depression in these patients was the selective serotonin reuptake inhibitors, where fluoxetine was the most common medication. Patients with depression had a lower mean absolute forced expiratory volume in 1 s (1.88 vs 2.48 L; P = .042), more than 5 total hospitalizations per year (4 vs 1; P = .012), and more outpatient CF exacerbations requiring treatment (1.5 vs 0; P = .023) per year than patients without depression. CONCLUSION: Identified risk factors may be used to increase depression screening of CF pediatric patients, allowing for early detection and screening in this potentially high-risk patient population. More studies are needed to determine efficacious treatment for depression in pediatric CF patients.