Impact of pegaspargase dose capping on incidence of pegaspargase-related adverse events in adults.

INTRODUCTION: Asparaginase derivatives are essential components of the treatment of acute lymphoblastic leukemia in adolescent and young adult patients. However, their associated toxicities limit wider use in older populations. This study seeks to determine if the practice of capping the pegaspargase dose at 3750 units reduces the risk of related adverse events in adults. METHODS: Adverse event data were retrospectively collected 28 days following each administration of pegaspargase in a single center. Doses were categorized as either capped (≤3750 units) (n = 57, 47.5%) or non-capped (>3750 units) (n = 63, 52.5%). The primary endpoint of this study was the composite incidence of serious pegaspargase-related adverse events, defined as grade 3 or higher. RESULTS: Of the 120 doses administered, 47 (39.2%) were administered to patients > 39 years. For the primary endpoint, 26 doses (45.6%) in the dose capped group versus 22 doses (34.9%) in the non-dose capped group were associated with serious pegaspargase-related adverse events (p = 0.23). Isolated laboratory abnormalities accounted for all hepatotoxicity and pancreatic toxicity events, while venous thromboembolism and bleeding occurred after 8.3% and 13.3% of doses, respectively. Multivariate analysis of the primary outcome to adjust for differences in baseline characteristics found no difference between groups (OR 2.56 (0.84, 7.77, p = 0.098)). CONCLUSIONS: The incidence of serious clinical toxicities was low in this study, particularly pegaspargase-related venous thromboembolism. This suggests that the practice of capping pegaspargase doses at 3750 units, coupled with vigilant monitoring and prophylaxis for pegaspargase-related adverse events, can allow for the inclusion of this drug in the treatment of older individuals.

Use of active learning and simulation to teach pharmacy students order verification and patient education best practices with oral oncolytic therapies.

INTRODUCTION: The primary objective of this study was to describe the incorporation of the flipped classroom model and use of real-life oncology patients to facilitate student learning of oral oncolytic best safety practices and patient counseling. The secondary objective was to assess the impact of the flipped classroom learning activity on students' perceived confidence. METHODS: This study was a prospective, single center, flipped classroom learning activity and pre/post assessment survey administered to third year doctor of pharmacy students enrolled in the Oncology Pharmacotherapy didactic elective in 2016 and 2017. A pre/post survey was used to assess student's perceived confidence with oral oncolytic best practice competencies. RESULTS: Ten students participated in the flipped classroom learning activity and survey. Five students completed both the pre- and postsurvey. The overall change in student's mean scores for their confidence of oral oncolytic competencies improved significantly from 3 to 4.1 on a 6-point Likert Scale (p = 0.03) following the learning activity. Students perceived confidence in performing oral oncolytic order verification increased following the implementation of a flipped classroom learning activity and use of real-life cancer oncology patients. CONCLUSION: This study describes the development and implementation of a flipped classroom learning activity and use of real-life patients with cancer that can be implemented at other institutions of higher education in a didactic or experiential learning environment. Additionally, this study demonstrated a potential benefit in student learning.

Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia.

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management.

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

Student confidence with oncology pharmacy competencies.

OBJECTIVE: The purpose of this study was to assess the change in student confidence to perform oncology pharmacy competencies before and after completing oncology didactic instruction using a flipped classroom approach. METHODS: First year doctor of pharmacy students completed a survey prior to the Applied Science and Therapeutics (AST) oncology module (pre-survey) and the same survey following the completion of the oncology module (post-survey). The survey consisted of questions addressing prior oncology pharmacy experience related to employment (research or patient care) and education, level of interest in oncology pharmacy, and level of confidence to perform thirteen oncology pharmacy competencies. RESULTS: One-hundred sixteen students completed the pre-survey and 35 completed the post-survey. Students completing both surveys reported greater confidence in all oncology pharmacy competencies (p < 0.0001) after instruction. The greatest increases in student confidence were related to chemotherapy dose calculations, patient education, and drug-drug interactions. CONCLUSIONS: The delivery of oncology content using flipped classroom instruction in the AST course successfully increased student confidence in ability to perform oncology pharmacy competencies. Cancer screening, cancer risk factors, and the preparation and dispensing of chemotherapy were competencies identified as needing greater emphasis in classroom instruction. Future studies are needed to assess student's knowledge and application of oncology pharmacy competencies in both the experiential and classroom settings.

Case report of capecitabine toxicity and use of uridine triacetate.

Fluorouracil and capecitabine are fluoropyrimidine chemotherapy agents that are commonly used for various cancers. These agents are generally well tolerated at standard doses; however, it has been reported that 31-34% of patients develop dose-limiting toxicities. Dihydropyrimidine dehydrogenase and thymidylate synthase play a major role in fluorouracil and capecitabine activity and toxicity. Uridine triacetate has shown promising results for the emergency treatment of patients who either receive an overdose of the cancer treatment fluorouracil or capecitabine or to treat patients who exhibit early-onset, severe, or life-threatening toxicity. We describe a case of a patient who developed capecitabine toxicity and was unsuccessfully treated with uridine triacetate.

Facilitating Home Hospice Transitions of Care in Oncology: Evaluation of Clinical Pharmacists' Interventions, Hospice Program Satisfaction, and Patient Representation Rates.

BACKGROUND: The importance of medication reconciliation and the pharmacist's role within the interdisciplinary team at the point of transition to home hospice is understudied. A transitions of care pilot initiative was developed to streamline the transition for patients at end of life from inpatient cancer center care to home hospice. The initiative consisted of using a hospice discharge checklist, pharmacist-led discharge medication reconciliation in consultation with the primary team responsible for inpatient care, review of discharge prescriptions, and facilitation of bedside delivery of discharge medications. METHODS: This was a single-center, prospective, pilot initiative. The objectives of this study were to characterize pharmacist interventions at the time of transition, to assess changes in hospice organizations' perceptions of discharge readiness, and to evaluate differences in representation rates with the implementation of the pilot discharge process. RESULTS: Fifteen patients in the preimplementation period and 12 patients in the postimplementation period were included. One hundred eleven pharmacist interventions were captured, an average of 9.3 interventions per patient, with an acceptance rate of 82.9% by providers. There was a statistically significant ( P = .035) improvement in hospice organizations' perceptions of discharge readiness. There was no difference in 30-day representation rates postdischarge ( P = 1). CONCLUSION: This well-received pilot initiative demonstrated an improvement in local hospice's perception of patient readiness for discharge and a high percentage of accepted pharmacist interventions during discharge medication reconciliation. A larger sample size of patients and longer follow-up period may be needed to demonstrate statistically significant improvements in representation rates postintervention.

Assessing the need for improved strategies and medication-related education to increase adherence for oral anticancer medications in the young adult oncology population.

Rationale Oral anticancer medication adherence is a critical factor in optimizing cancer treatment outcomes and minimizing toxicity. Although potential adherence barriers exist, it is not well understood how these factors impact adherence. Methods This is a prospective, single-center, patient survey-based study conducted at the University of Maryland Greenebaum Comprehensive Cancer Center including 18- to 39-year-old patients who have been actively taking an oral anticancer medication for at least one month from 1 April 2013 to 1 April 2016. The primary objective of this study is to describe institutional practices for medication education and adherence monitoring practices as perceived by young adult patients at the University of Maryland Greenebaum Comprehensive Cancer Center and to describe practice consistency with recommendations from the American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. The secondary objectives include patient-reported facilitators and barriers to oral anticancer medication adherence. Results Seventeen patients completed the survey; 24% ( n = 4) of patients denied receiving information about what to do in case of a missed dose. The most common facilitators of adherence include understanding of disease and treatment (88%, n = 15), perceived severity of illness (82%, n = 14), and use of oral anticancer medications (82%, n = 14). The most common barriers to adherence are side effects (59% n = 10), forgetfulness (47%, n = 8), and depressive symptoms (35%, n = 6). Conclusion Based on patient-reported guideline adherence, improvement is needed in including family, caregivers, and others in the education process as well as providing education about plan for missed doses and drug-drug and drug-food interactions. The strengths of the current medication education and adherence monitoring practices as perceived by the young adult patient population include education about the purpose and goals of treatment, the planned duration and schedule, side effects, and when to seek medical attention. The data collected from this survey can aid in future development and implementation of interventions aimed at improving medication adherence, such as integrating clinical pharmacy services into oral chemotherapy monitoring and education process.

Drug-drug interactions in patients receiving tyrosine kinase inhibitors.

Rationale Tyrosine kinase inhibitors are increasingly used in the treatment of cancer. Drug interactions involving tyrosine kinase inhibitors are commonly encountered in clinical practice. The objective of this study was to describe the frequency of tyrosine kinase inhibitor-associated drug interactions among a cohort of oncology patients. Methods Adult patients were included who presented to either of two outpatient oncology practices and were prescribed a tyrosine kinase inhibitor during 2 January 2013 to 1 January 2015. Demographic and medication data were abstracted from electronic medical records. Lexicomp®, Micromedex Solutions®, and medication labeling were utilized to identify potential interactions between tyrosine kinase inhibitors and concomitant medications. Interactions were then assessed by the investigators for clinical significance. The primary outcome was the frequency of significant drug interactions involving tyrosine kinase inhibitors and concomitant medications. Secondary outcomes included describing the nature and clinical impact of interactions, and describing interactions by medication class. Results A total of 356 patients were identified for analysis, in whom 244 potential interactions were identified, and 109 (44.7%) of which were considered severe. Decreased tyrosine kinase inhibitor absorption due to acid suppressive therapy and CYP3A4 interactions were the most frequent mechanisms of potential subtherapeutic and supratherapeutic concentrations, respectively. Potential clinical consequences included QTc prolongation ( n = 53, 48.6%), decreased tyrosine kinase inhibitor concentration ( n = 53, 48.6%), and increased tyrosine kinase inhibitor concentration ( n = 3, 2.8%). Conclusions Safer alternative therapy and/or more frequent clinical monitoring should be considered if an interaction poses a significant risk of increased tyrosine kinase inhibitor toxicity or decreased tyrosine kinase inhibitor efficacy. Oncology pharmacists can play a role in screening for tyrosine kinase inhibitor-associated interactions, recommending alternative therapies or dosing strategies, and monitoring tyrosine kinase inhibitor efficacy and toxicity.

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.