Alexandra Shillingburg

Superior Serum Concentrations with Posaconazole Delayed-release Tablets Compared to Suspension Formulation in Hematological Malignancies.

ABSTRACT Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

Safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting in pediatric patients: a prospective, observational study.

Pediatric patients between the ages of 12 months and 17 years with a confirmed malignancy who were scheduled to receive aprepitant as part of triple therapy antiemetic prophylaxis for a cycle of moderately‐ or highly emetogenic chemotherapy were eligible for enrollment. Patients were evaluated for the incidence of nausea, episodes of emesis, interference with activities of daily living (ADLs), and appetite through utilization of a patient survey. Eleven patients were enrolled for a total of 20 patient encounters, mean age 9.55 ± 4.85 (range, 12 months–17 years). Aprepitant was well‐tolerated and complete response (CR) rate was 38.9%. Pediatr Blood Cancer 2014;61:1111–1113.

Evaluation of Serum Posaconazole Concentrations in Patients with Hematological Malignancies Receiving Posaconazole Suspension Compared to the Delayed-Release Tablet Formulation

Posaconazole (PCZ) is frequently used for prophylaxis against invasive fungal infections (IFI) in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is commercially available as an oral suspension (PCZ-susp) and as a delayed-release tablet (PCZ-tab). Differences in absorption and bioavailability between these formulations may result in variability in serum posaconazole concentrations. The primary objective of this retrospective analysis was to compare attainment of goal serum posaconazole steady state concentrations (Css) ≥ 700 ng/ml in patients with AML/MDS undergoing induction chemotherapy receiving PCZ-susp 600–800 mg per day (N = 118) versus PCZ-Tablet 300 mg twice daily for one day, followed by 300 mg daily (N = 64). Sixty-two patients (97%) in the PCZ-tab group compared to 20 patients (17%) in the PCZ-susp group achieved goal Css  (P < 0.0001). Median posaconazole serum Css was 1,665 ng/ml (522–3,830 mg/ml) in the PCZ-tab group versus 390 ng/ml (51–1,870 ng/ml) in the PCZ-susp group (P < 0.0001). There was no difference in hepatotoxicity, QTc prolongation, or breakthrough IFI. Patients receiving PCZ-tab were significantly more likely to achieve goal Css and demonstrated higher Css versus patients receiving PCZ-susp. Prospective studies are needed to assess the potential correlation of serum concentrations with efficacy and toxicity.

Aprepitant and Fosaprepitant Use in Children and Adolescents at an Academic Medical Center

OBJECTIVE To describe the use of aprepitant and fosaprepitant, a neurokinin 1 (NK-1) receptor inhibitor, in children and adolescents at a large academic medical center, for the prevention and management of chemotherapy-induced nausea and vomiting (CINV). METHODS A retrospective chart review was conducted using an electronic medical record system to evaluate the use of aprepitant and fosaprepitant in all pediatric patients that were discharged from a single academic medical center between February 25, 2009 and May 25, 2012. RESULTS Twenty-six patients were included in this review and received a total of 287 doses over the span of 114 cycles. Mean age was 10.1 years, with a range of 11 months to 17 years old. In 16 of 26 patients, aprepitant was used as the primary prophylaxis. Of those patients who received primary prophylaxis, 6 of 16 received it for highly emetogenic chemotherapy, and 10 of 16 received it for moderately emetogenic chemotherapy. Intravenous fosaprepitant was used in 7 of 26 patients, ages 13 to 17 (median 14) years old. No adverse effects attributable to aprepitant were reported. CONCLUSIONS Use of aprepitant and fosaprepitant in pediatric patients appeared to be well tolerated. No currently published reports data using aprepitant in a patient younger than 32 months old, whereas we reported its use in patients as young as 11 months old.

Outcomes of Six-Dose High-Dose Cytarabine as a Salvage Regimen for Patients with Relapsed/Refractory Acute Myeloid Leukemia

Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10–12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy. We present a retrospective review of 26 consecutive patients with RR-AML receiving single agent cytarabine 3 g/m2 intravenously every 12 hours on days 1, 3, and 5 for a total of six doses (HiDAC-6). Median follow-up for surviving patients was 10.4 months (range 1.6–112.2 months). Complete remission was obtained in 62% (54% CR and 8% CRi) of the patients. The median relapse-free survival (RFS) was 22.3 months (range 0.7–112 months), event-free survival (EFS) was 4.7 months (range 0.5–112 months), and the overall survival (OS) was 9.6 months (range 1–112 months). Thirty-five percent of patients were able to subsequently proceed to allo-HCT. Treatment-related toxicities included neutropenic fever (38%), infection (35%), neurotoxicity (8%), and skin toxicity (8%). This is the first study to demonstrate HiDAC-6 as an active treatment option for younger patients with RR-AML which can effectively serve as a bridge to allo-HCT without significant toxicity.

Oral Antineoplastic Agents: Assessing the Delay in Care

The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additional information, including prescribed medication, indication, insurance coverage, patient assistance program use, dispensing pharmacy, and prior authorization requirements. The data was analyzed through multivariate statistical analysis and used to identify risk factors that may significantly increase the time to medication receipt. A total of 58 patients were included in the study. A median of 8 days elapsed between when the medication was prescribed and when it was received by the patient. Medication prescribed, absence of a Risk Evaluation Mitigation Strategies (REMS) program, and insurance type are factors that increased time to medication receipt. An understanding of the median time involved, as well as factors affecting the time to delivery of prescriptions, will help healthcare providers better plan and prepare for the use of oral antineoplastic agents.