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.

Using Electronic Health Record Technology to Teach Inpatient Medication Order Verification to Pharmacy Students.

Objective. To measure Doctor of Pharmacy (PharmD) students' confidence and assess their performance when processing inpatient medication orders, and to determine students' opinions regarding electronic health record (EHR) technology. Methods. Using an EHR platform, students processed inpatient medication orders during two laboratory sessions and one assessment. Each student was assigned one unique patient per session and was given three inpatient orders to process. Medication errors were randomly imbedded in the medication orders. Students needed to determine if the order was acceptable or required flagging because of an identified error. Pre- and post-activity surveys were administered to assess students' level of confidence and perceptions regarding the simulated EHR activities. Aggregate performance scores were compared between a cohort of PharmD students that used an EHR for the activity versus those who completed the activity the previous year using a paper-based medication form. Results. One hundred eight of 158 students (68%) in the course had pre- and post-activity survey data that could be paired. Less than one quarter (24%) of students had prior work experience in a hospital setting. For the medication verification questions, the confidence levels of students who used the EHR doubled and in some cases tripled pre- and post-EHR implementation. In each of the areas surveyed, results for all medication order processing statements were significant. Student performance improved significantly compared with that of those who completed the activity the previous year using a paper-based medication form. Post-EHR implementation, a significantly lower number of students felt that learning to use EHR technology would prepare them for advanced pharmacy practice experiences. Conclusion. Exposure to EHR technology improved PharmD students' confidence and performance scores related to processing inpatient medication orders. These findings support the continued use of an EHR platform in skills-based activities.

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.

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.

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

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.

Board-Certified Oncology Pharmacists: Their Potential Contribution to Reducing a Shortfall in Oncology Patient Visits.

PURPOSE: With an aging US population, the number of patients who need cancer treatment will increase significantly by 2020. On the basis of a predicted shortage of oncology physicians, nonphysician health care practitioners will need to fill the shortfall in oncology patient visits, and nurse practitioners and physician assistants have already been identified for this purpose. This study proposes that appropriately trained oncology pharmacists can also contribute. The purpose of this study is to estimate the supply of Board of Pharmacy Specialties-certified oncology pharmacists (BCOPs) and their potential contribution to the care of patients with cancer through 2020. METHODS: Data regarding accredited oncology pharmacy residencies, new BCOPs, and total BCOPs were used to estimate oncology residencies, new BCOPs, and total BCOPs through 2020. A Delphi panel process was used to estimate patient visits, identify patient care services that BCOPs could provide, and study limitations. RESULTS: By 2020, there will be an estimated 3,639 BCOPs, and approximately 62% of BCOPs will have completed accredited oncology pharmacy residencies. Delphi panelists came to consensus (at least 80% agreement) on eight patient care services that BCOPs could provide. Although the estimates given by our model indicate that BCOPs could provide 5 to 7 million 30-minute patient visits annually, sensitivity analysis, based on factors that could reduce potential visit availability resulted in 2.5 to 3.5 million visits by 2020 with the addition of BCOPs to the health care team. CONCLUSION: BCOPs can contribute to a projected shortfall in needed patient visits for cancer treatment. BCOPs, along with nurse practitioners and physician assistants could substantially reduce, but likely not eliminate, the shortfall of providers needed for oncology patient visits.

White blood cell growth factor use in an outpatient oncology clinic: Lessons and opportunities learned.

The increased use and high cost associated with white blood cell growth factors at our outpatient oncology clinic has prompted this evaluation. The objectives of this study were to categorize the indication for use of pegfilgrastim and filgrastim; evaluate the administration of these white blood cell growth factors; identify opportunities for cost savings; and identify ways to increase prescriber adherence to evidence-based practice guidelines. This medication use evaluation study involved retrospective data collection from patient medical records. Adult oncology patients treated in the outpatient oncology clinic who received filgrastim or pegfilgrastim were identified and included in this study. Computerized patient records were used to collect data on patient demographics, risk factors for febrile neutropenia, prescribing patterns for filgrastim and pegfilgrastim, and chemotherapy regimens. The number of pegfilgrastim and filgrastim doses were predominately used for primary prophylaxis following chemotherapy treatment. Of the 234 total doses of pegfilgrastim used in the setting of primary prophylaxis, 28 (12%), 134 (57%), and 72 (31%) doses were given to patients receiving chemotherapy regimens associated with a high risk (>20%), intermediate risk (10-20%), and low risk (<10%) of febrile neutropenia, respectively. The total number of pegfilgrastim doses used in secondary prophylaxis was 78; 20 (26%) and 58 (74%) of these doses were given to patients receiving chemotherapy regimens associated with an intermediate risk and low risk of febrile neutropenia, respectively. This study revealed a significant portion of prescribed growth factor use that was not in accordance with clinical practice guidelines.

Oral chemotherapy handling and storage practices among Veterans Affairs oncology patients and caregivers.

PURPOSE: This questionnaire-based study was designed to identify the oral chemotherapy medication handling, storage, and disposal practices among cancer patients and their caregivers. METHODS: This was a single-center observational survey study approved by the Investigational Review Board and VA Research & Development Committee. Patients were eligible for inclusion if they had an active order for an oral antineoplastic medication and an appointment at the oncology clinic. A questionnaire related to the storage, handling, disposal, patient education and counseling, and patients' perception of safety of oral antineoplastic medications was developed and given to patients in the clinic. Survey responses were analyzed using descriptive statistics. RESULTS: A total of 45 surveys were given to eligible patients in the oncology clinic and 42 surveys were returned to the study team. The majority, 40 participants (95%) were male. Participants ranged in age from 51 to 85 years (median, 65 years). Thirty-eight patients (90.5%) responded that the medication was stored away from extreme heat, cold, and humidity. Thirty-two patients (76%) reported keeping their medications in the original container. Hand washing was not a consistent practice among patients. Eleven patients (26%) reported always washing their hands after handling their anticancer medication; another 6 (14%) responded "sometimes". Of the 42 participants who answered, only 6 patients (14%) reported always or sometimes wearing gloves. CONCLUSION: The majority of patients responding to this survey store their oral anticancer medications appropriately, but patients' and caregivers' handling and disposal practices are inconsistent and frequently do not follow the published recommendations.

An interprofessional web-based approach to providing breast cancer education.

This paper describes the process that nursing, social work, and pharmacy faculty at a state university undertook to develop interprofessional web-based breast cancer education modules for incorporation into required curriculum. Eight web modules initially developed to educate baccalaureate nursing students on breast cancer were revised and expanded at each health professional school to include discipline-specific information pertinent to social work and pharmacy scope of practice. A specialized internet-accessible web-delivered application was constructed consisting of eight reusable learning objects, or modules, including epidemiology, risk factors and screening, diagnosis, staging and grading, treatment, survivorship, disparities, and metastatic breast cancer. These modules were organized for easy integration into existing courses and allowed for an efficient means of providing expert, evidence-based content. Innovative methods to integrate nursing, social work, and pharmacy education are needed to achieve an effective interprofessional educational approach to teaching breast cancer content.

New developments in management of oral mucositis in patients with head and neck cancer or receiving targeted anticancer therapies.

PURPOSE: Issues surrounding the prevention and management of severe oral mucositis in patients with head and neck cancer and patients receiving targeted anticancer therapies are reviewed. SUMMARY: Cancer therapy-related mucositis is associated with many negative and potentially life-threatening sequelae. Patients receiving chemoradiotherapy for head and neck cancer are at high risk for severe oral mucositis, but there are currently no definitive recommendations on pharmacologic preventive strategies. Recently published evidence on the use of palifermin to combat oral mucositis during chemoradiotherapy for head and neck cancer is encouraging, with two randomized controlled trials indicating an absolute risk reduction of about 15%; however, palifermin use was not associated with lower rates of mucositis-related treatment delays or chemotherapy dosage reductions, and concerns about optimal dosage and cost-benefit issues persist. Oral mucositis due to targeted therapies for renal cell carcinoma and other disorders (e.g., kinase inhibitors, mammalian target of rapamycin inhibitors) is generally less severe than mucositis caused by conventional cytotoxic chemotherapy. For both types of mucositis, recommended management strategies include good oral hygiene and optimal pain control. Research in this area continues to be complicated by investigators' use of varying terminology and mucositis classification schemes. CONCLUSION: Palifermin appears to reduce the frequency of oral mucositis in patients treated for head and neck cancer, but its place in therapy has not been determined. Although the oral complications of targeted therapies are clinically distinct from those of conventional cytotoxic therapy, the literature recommends similar palliative management strategies for both.

Racial/ethnic and age disparities in chemotherapy selection for colorectal cancer.

OBJECTIVES: To test the hypotheses that African American patients and older patients with stage IV colorectal cancer were less likely to receive newer chemotherapy agents. STUDY DESIGN: Retrospective cohort design. METHODS: Among 5068 Surveillance, Epidemiology, and End Results-Medicare patients diagnosed as having stage IV colorectal cancer between 2000 and 2002, a total of 2466 received chemotherapy and were included in the analysis. Irinotecan hydrochloride was the first of the "newer" chemotherapy agents and was marketed in 2000 as a first-line add-on agent. Descriptive statistics were generated, and a multivariable logistic regression was run to estimate the odds of receiving irinotecan among African American patients and older patients and within 2 months of chemotherapy initiation. RESULTS: African American patients had lower odds of initiating treatment with a newer chemotherapy than white patients (adjusted odds ratio, 0.641; 95% confidence interval, 0.453-0.907). An age disparity was also found, with all older age groups being significantly less likely to initiate treatment with a newer chemotherapy than the youngest age group: the adjusted odds of receiving newer chemotherapy agents (relative to patients aged 66-70 years) were lower and significant among patients aged 71 to 75, 76 to 80, and older than 80 years (odds ratios, 0.708, 0.527, and 0.213, respectively). CONCLUSIONS: Disparities in chemotherapy selection exist among patients receiving chemotherapy for stage IV colorectal cancer. On initiating chemotherapy, African American patients and older patients were less likely to receive a newer agent.

Efficacy of aprepitant in patients receiving high-dose chemotherapy with hematopoietic stem cell support.

PURPOSE: This study describes the efficacy of aprepitant in preventing nausea and vomiting associated with high-dose chemotherapy in hematopoietic stem cell transplant (HSCT) patients. Our hypothesis is the addition of aprepitant to 5-HT3 antagonists and dexamethasone would result in a 20% increase in complete response (CR) rates compared to CR rates from published studies evaluating antiemetic regimens without aprepitant. METHODS: Adult HSCT patients receiving high-dose chemotherapy and aprepitant as part of their antiemetic regimen were included following written informed consent. CR was defined as no emesis, none to mild nausea, and no breakthrough antiemetic use. Daily patient diaries were used on days 1 through 7 following high-dose chemotherapy to collect severity of nausea, emetic episodes, breakthrough antiemetic use, and any antiemetic related side effects. RESULTS: We accrued a total of 42 patients. CR rates ranged from 42.9% to 73.8% for the 7 days. The average CR rate for days 1 through 7 was 54%. Fourteen patients (33%) maintained a complete emetic response on each of the 7 days. The average CR rate for published studies in HSCT patients receiving an antiemetic regimen without aprepitant is 57%. Most common adverse effects reported by patients receiving aprepitant were hiccups (33%) and drowsiness (33%). CONCLUSIONS: The addition of aprepitant failed to meet our primary endpoint of increasing CR rates by 20%. The lower than expected CR rate was attributed to use of breakthrough antiemetics. Aprepitant did result in preventing emesis in the majority of patients and was associated with minimal side effects.

Lapatinib: a dual tyrosine kinase inhibitor for metastatic breast cancer.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug and food interactions, dosage and administration, and role in therapy of lapatinib in metastatic breast cancer are reviewed. SUMMARY: Lapatinib is a small-molecule tyrosine kinase inhibitor that dually targets human epidermal growth factor receptors 1 and 2 (HER2). Unlike trastuzumab, lapatinib enters the cell and binds to the intracellular domain of the tyrosine kinase receptor, allowing for complete blockage of the autophosphorylation reaction and a complete halt to the downstream cascade of events. After oral administration, lapatinib reaches peak plasma levels within approximately 4 hours, steady-state levels within six to seven days, and has a half-life of 24 hours. Combination therapy with lapatinib and capecitabine has demonstrated superior time to progression compared with capecitabine monotherapy for the treatment of HER2-positive metastatic breast cancer refractory to anthracycline-, taxane-, and trastuzumab-containing regimens. Unlike trastuzumab, lapatinib is an orally active agent with promising clinical activity in metastatic breast cancer and is associated with a better adverse-effect profile. The most frequently reported adverse events in patients receiving combination therapy with lapatinib and capecitabine were diarrhea and hand-foot syndrome. Ongoing research has further evaluated the safety of lapatinib regarding cardiac effects and found that the majority of left ventricular ejection fraction decreases from baseline were asymptomatic and reversible. CONCLUSION: Lapatinib has demonstrated efficacy in combination with capecitabine in patients with previously treated HER2-positive metastatic breast cancer. In patients with metastatic disease refractory to trastuzumab-, anthracycline-, and taxane-containing regimens, the addition of lapatinib to capecitabine may extend the time to disease progression and progression-free survival.