Excellent Tolerability of Ifosfamide and Mesna Via Continuous Infusion in a Pediatric Patient Population.

Ifosfamide is an antitumor agent with activity against various malignancies in pediatric patients. As a prodrug, ifosfamide requires metabolic activation, which occurs via a saturable, multistep equilibrium-based process. Due to these metabolic characteristics, the method of administration can affect its therapeutic and toxic effects. This single-center, retrospective review describes the tolerability of continuous infusion and bolus administration of ifosfamide in 10 pediatric patients with Ewing sarcoma. The primary objective was to report the hematologic toxicities of patients with differing administration methods. Secondary objectives included collecting information on nonhematologic toxicities and incidence of treatment delays and dose reductions. Ultimately, 48 cycles of ifosfamide were administered as bolus administration and 24 as continuous infusion. Patients receiving bolus administration had lower hemoglobin and platelet nadirs resulting in more transfusions and treatment delays when compared proportionally to continuous infusion. With the results of this case series, continuous infusion ifosfamide appears to be safe and feasible for outpatient administration and may offer an advantage from a hematologic adverse event profile but would need to be confirmed in a larger cohort.

Rapid-Infusion Rituximab in a Pediatric Population.

OBJECTIVES: The use of rapid rituximab infusion in certain pediatric populations has generally been regarded as safe. The safety of our institution's rapid rituximab protocol was evaluated. METHODS: The primary end point was the number of and severity of adverse drug reactions. Secondary end points included a description of the patient population defined by the indication, dose, and number of rituximab infusions administered. Additionally, the difference in infusion times in hours of those receiving rapid rituximab infusions versus the theoretical infusion time of subsequent administration rate schedules was defined. RESULTS: A total of 88 infusions for 22 patients were reviewed. No dose-limiting adverse reactions were observed. Three patients experienced grade 1 isolated infusion-related adverse events during a single infusion encounter. Two of the three patients received additional doses of rapid rituximab infusions without incident, whereas the other patient no longer required rituximab therapy. CONCLUSIONS: The use of a 90-minute rituximab infusion protocol in pediatric patients with non-rheumatic diseases was well tolerated.

Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome.

Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.

Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations.

Individuals who carry the CYP2C19*17 gain-of-function allele have lower voriconazole exposure and are therefore at risk of failing therapy. Utilizing CYP2C19 genotype to optimize voriconazole dosage may be a cost-effective method of improving treatment outcomes. However, there are limited data describing what initial voriconazole dosage should be used in those with increased CYP2C19 metabolic capacity. Herein, we present a case report of a pediatric CYP2C19 rapid metabolizer (i.e., CYP2C19*1/*17) requiring a voriconazole dosage of 14 mg/kg twice daily (usual pediatric dosage ranges from 7 to 9 mg/kg twice daily). This case report supports the clinical utility of using CYP2C19 genotype to guide voriconazole dosing, and provides data for establishing an initial voriconazole dose in pediatric CYP2C19 rapid metabolizers.