Search

The endocannabinoid system (ECS) is a complex cell-signaling system. To address the growing need of analytics capturing endocannabinoid levels to investigate the ECS, we developed and validated an assay for the quantitative analysis of 14 endocannabinoids and congeners. A simple extraction using protein precipitation with acetonitrile followed by online-trapping high-performance liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS) was used to monitor the levels of 14 endocannabinoids in plasma. The assay was validated and intra-run and inter-run accuracies and imprecisions as well as matrix effects, recoveries, and sample stabilities were determined. As a proof of concept, a subset of study samples after naturalistic administration of Cannabis flower and concentrate was analyzed. With the exception of N-oleoyl dopamine and oleamide, all endocannabinoids fulfilled the predefined acceptance criteria. Reproducible recoveries and no significant matrix effects were observed. Sample stability was an issue. Analysis of the proof-of-concept study samples revealed a significantly (p = 0.006) higher concentration of docosatetraenoyl ethanolamide in concentrate users (300 ± 13 pg/mL) compared to flower users (252 ± 11 pg/mL). A robust, sensitive high-throughput assay for the quantitation of 14 endocannabinoids and congeners was successfully validated. Our study showed that it is mandatory to (A) appropriately stabilize samples and (B) separate and separately quantify 1-AG and 2-AG; otherwise, study results are unreliable. The analysis of study samples from Cannabis flower users versus Cannabis concentrate users revealed higher levels of docosatetraenoyl ethanolamide and anandamide (n.s.) in high THC concentrate users in accordance with the existing literature, supporting the validity of the assay measurements. Graphical abstract.

Introduction Filgrastim is a human granulocyte colony-stimulating factor (G-CSF). There is limited data on dosing filgrastim in obesity. The objective of this study was to compare filgrastim pharmacokinetic parameters for morbidly obese and non-obese patients after a single subcutaneous dose of filgrastim dosed per actual body weight. Methods This prospective, matched-pair study (NCT01719432) included patients ≥18 years of age, receiving filgrastim at 5 mcg/kg with a weight >190% of their ideal body weight (IBW) for "morbidly obese" patients or within 80-124% of IBW for matched control patients. The control group was prospectively matched for age (within 10 years), degree of neutropenia, and gender. Filgrastim doses were not rounded to vial size, to allow more accurate assessment of exposure. Blood samples were collected at 0 (prior to dose), 2, 4, 6, 8, 12, and 24 hours after the first subcutaneous administration of filgrastim. Results A total of 30 patients were enrolled in this prospective pharmacokinetic study, with 15 patients assigned to each arm. Non-compartmental analysis showed that the systemic clearance (Cl) was 0.111 ± 0.041 mL/min in the morbidly obese group versus 0.124 ± 0.045 mL/min in the non-obese group (p=0.44). Additionally, the mean area under the curve (AUC0-24h ) was 49.3 ± 13.9 ng/mL x min in the morbidly obese group versus 46.3 ± 16.8 ng/mL x min in the non-obese group (p=0.6). No differences were seen in maximum concentrations (Cmax ) between the two groups (morbidly obese: 48.1 ± 14.7 ng/mL vs. non-obese: 49.2 ± 20.7 ng/mL (p=0.87)). The morbidly obese group had a numerically higher, but not statistically significant, increase in time to maximum concentration (Tmax ) compared to the non-obese group (544 ± 145 min vs 436 ± 156 min (p=0.06), respectively). Conclusion Calculating subcutaneous filgrastim doses using actual body weight appears to produce similar systemic exposure in morbidly obese and non-obese patients with severe neutropenia.

Gender disparity exists in leadership roles within healthcare. While the majority of the healthcare workforce is comprised of women, significantly fewer women occupy leadership positions, particularly at executive and board levels. As the field of oncology pharmacy continues to rapidly expand and evolve, an assessment of the current state of women in oncology pharmacy leadership roles is vital to the growth and development of the profession. In the fall of 2017, the Hematology/Oncology Pharmacy Association (HOPA) hosted a summit to explore leadership issues facing women in oncology pharmacy which have the potential to affect our membership and our profession. This meeting included invited participants from across the fields of oncology and pharmacy and was part of HOPA’s strategic leadership initiative developed through the work of the HOPA Leadership Development Committee in 2016. This promotes a primary goal of HOPA, which is to support oncology pharmacists as they assume leadership roles within their practices and within healthcare to assure oncology pharmacy is integrated into cancer care. The purpose of this white paper is to (1) summarize key issues that were identified through a membership survey; (2) review ongoing efforts to address the needs of female oncology pharmacists in leadership development; (3) serve as a call to action for individuals and professional organizations to assist with and disseminate these efforts and highlight available resources, and (4) to provide practical steps to meet the needs of individuals, training programs, and institutions/employers.

The development of BCR-ABL-targeting tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia (CP CML) from a disease with a terminal prognosis to a treatable chronic illness. Long-term treatment with tyrosine kinase inhibitors means that patients have to be clinically managed and monitored over extended periods of time, thus a patient-centered, medically integrated, and multidisciplinary oncology healthcare team is required to support patients through their journey. Pharmacists work with patients, physicians, and the wider support team to select the optimum therapy plan for a given patient. These decisions are based on risk factors, comorbidities, concomitant medications, and personal circumstances and pharmacists advise on the efficacy and safety of different treatment options. Additionally, pharmacists are a key point-of-contact and resource for monitoring patient response to treatment, identifying and managing adverse events and drug–drug interactions, any subsequent therapy plan modifications, and, potentially, treatment-free remission. Pharmacists also assist with patient education, medication adherence, and financial discussions with patients throughout the long course of the disease. This review provides an overview of BCR-ABL tyrosine kinase inhibitors, discusses the role of the medically integrated pharmacy team, and suggests strategies that pharmacists can use in patient management and clinical decision-making to optimize the treatment of CP CML.

Mucositis is a significant complication of intensive chemotherapy or hematopoietic cell transplantation (HCT), with few treatment options. Ketamine mouthwashes have been used for pain relief, but supporting evidence is limited. The primary objective of this study was to assess the reduction in pain intensity of stomatodynia and odynophagia compared to baseline assessment. This open-label, prospective, phase II interventional study (NCT01566448) was conducted from February 2012 through July 2015. Patients with grade 3 or 4 oral mucositis according to the World Health Organization (WHO) scale as a result of chemotherapy were treated with ketamine mouthwash 20 mg/5 mL four times daily and every 4 h as needed. Thirty patients were enrolled and a total of 136 assessments were conducted. A statistically significant reduction in pain scores of 2 and 3 points was achieved after 1 h and 3 days, respectively (p

For an outpatient cancer center to operate efficiently, optimizing the use of chair time is essential. Allogeneic hematopoietic cell transplant (allo-HCT) recipients are seen frequently in this setting after hospital discharge and regularly for several months thereafter. Aggressive electrolyte replacement is commonly required in these patients, primarily due to renal wasting with calcineurin inhibitor use. Frequent intravenous (IV) magnesium repletion, requiring several hours of infusion time, is often needed in these patients to adequately manage their magnesium deficiencies. The purpose of this study is to explore the impact of extending the infusion rate of intravenous magnesium sulfate on the frequency and degree of IV magnesium replacements required in allo-HCT recipients. We conducted a retrospective study to compare two cohorts of patients administered IV magnesium sulfate at a rate of 4 g/1 h versus 4 g/2 h. A total of 103 continuous patients were assessed in two groups as cohort 1 at the 4 g/1 h rate and cohort 2 at the 4 g/2 h rate. Cohort 1 required less IV magnesium per outpatient visit (median 2.2 vs. 2.9 g/visit, P = 0.0211) and less total IV magnesium replacement through day +100 (median 68 vs. 85 g, P = 0.0479) than cohort 2. These data suggest that there is no apparent benefit of prolonging magnesium infusion from 1 to 2 h in our outpatient allo-HCT population.

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.

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.

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/m2intravenously 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.

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.

Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P .001). The median day 1 yield of CD34(+) cells was not significantly different (median, 2.2 × 10(6) cells/kg in ICE versus 1.9 × 10(6) cells/kg in upfront plerixafor versus 1.7 × 10(6) cells/kg in JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P .001) and mean time to platelet engraftment was 13.7 days (±.7) in ICE versus 20.3 days (±1.6) in routine plerixafor versus 17.1 days (± .9) in JIT group (P .001). Red blood cell transfusions were significantly higher in the chemo-mobilization group (34.3% versus 0 versus 3.2% versus 1, P .001) and so were the platelet transfusions (22.9% versus 0 versus 0, P .001). Excluding the cost of chemotherapy administration, chemo-mobilization was associated with significantly less mobilization cost (average cost $17,601.76 in ICE versus $28,963.05 in routine and $25,679.81 in JIT, P .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.

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. © 2013 Wiley Periodicals, Inc.

The 95 degrees angled blade plate is an accepted standard for plating subtrochanteric femoral fractures but can be technically demanding and often requires extensive soft tissue exposure. Proximal femoral locking plates (PFLPs) have been developed for subtrochanteric and pertrochanteric fractures and are potentially easier to apply with less soft tissue dissection. Clinical experience has raised concerns regarding the strength of the PFLP. The purpose of our study was to compare the relative stability of two designs of PFLP with the 95 degrees angled blade plate under loads simulating the first 3 months of progressive weight bearing after fracture fixation.A comminuted subtrochanteric femoral fracture model was created with a 2-cm gap below the lesser trochanter in 15 synthetic femora. Fracture fixation of three plates (95 degrees angled blade plate [blade plate], the original version of the PFLP [O-PFLP], and the newest version of the PFLP [N-PFLP]), all manufactured by Synthes, Inc., Paoli, PA, was tested under progressive cyclic loading to reproduce progressive weight bearing during 3 months after fracture fixation. The force and number of cycles to reach 5 mm of displacement of the femoral head or failure of the implant were compared for each implant.N-PFLPs were significantly stiffer than blade plates and O-PFLPs (P = 0.01) and had a trend toward withstanding more cycles before failure (P = 0.06). All five O-PFLPs demonstrated catastrophic fatigue failure before completion of the protocol. One each of the blade plates and the N-PFLPs failed to complete the protocol (P = 0.04).In the model studied, N-PFLPs were shown to have biomechanical properties that were at least equivalent to those of the blade plate. The fatigue failures of O-PFLPs mirrored our clinical experience. Use of the N-PFLP might be a viable alternative fixation method for comminuted subtrochanteric femoral fractures that currently are treated with blade plates.

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 ( C ss ) 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 C ss 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 C ss assessment after at least 7 days of therapy were eligible. The median C ss 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 C ss and with the probability of achieving therapeutic goals without worsening of adverse effects.

Drug-induced immune hemolytic anemia (DIIHA) is rare, with only 1 patient in 1 million affected by the condition.1 Garratty identified 125 drugs indicated in DIIHA of which 11% were antineoplastic agents, and neither paclitaxel nor albumin-bound paclitaxel were included.2 In addition, we did not find any reports in our own search of the literature. Taxanes are known to cause anemia as a result of their myelosuppressive effects, but an immune hemolysis is rare. To our knowledge, we present here the first case of DIIHA with nab-paclitaxel.