Evaluation of a Pharmacist-Developed, Nurse-Driven Protocol for Management of Parenteral Anticancer Therapy Infusion Reactions in an Ambulatory Infusion Center.

PURPOSE: Intravenous anticancer therapy can be associated with hypersensitivity- and/or infusion-related reactions (IRRs) which may result in life-threatening symptoms. As part of a quality improvement project, oncology pharmacists developed and implemented a nurse-driven, symptom-based IRR protocol. The objective of the evaluation was to evaluate IRR treatment failure after implementation of a symptom-based protocol in an ambulatory infusion center. Secondary objectives included determining the most common anticancer agents requiring IRR treatment, documentation of ED visits or hospital admissions within 72 h of treatment, documentation of mortality due to an IRR, and evaluating whether there were multiple documented IRRs to the same medication. METHODS: A total of 456 patients, who received an infusion of anticancer therapy at Grady Health System (GHS) between February 2014 and March 2018, were retrospectively evaluated. Patients were included if they received a protocol-specific medication for infusion reaction management of a parenterally administered anticancer agent. The primary outcome was the rate of treatment failure within 72 h of treatment for an IRR. RESULTS: Seventy-eight patients experiencing 108 IRRs were included in the analysis. Five percent of IRRs consisted of rigors only, 57% of IRRs were mild/moderate severity, 31% of IRRs were severe/anaphylactic severity and 7% of IRRs were rigors in addition to a mild/moderate/severe reaction. Of the 108 IRRs, treatment failure within 72 h was observed in eight reactions; six were evaluated in the emergency department and two required a hospital admission. Overall, 93% of reactions resolved in the infusion center and patients were discharged home; there were no patient deaths. The most common offending agents were paclitaxel and oxaliplatin. CONCLUSION: Following implementation of a novel pharmacist-developed, symptom-based nurse-driven protocol, infusion reaction treatment failure occurred in 7% of IRRs evaluated. Although the failure rate was low, additional nurse education and improved access to protocol-directed medications may optimize use of the protocol.

Baseline basophil and basophil-to-lymphocyte status is associated with clinical outcomes in metastatic hormone sensitive prostate cancer.

BACKGROUND: Biomarkers have the potential to provide clinical guidance, but there is limited data for biomarkers in metastatic hormone sensitive prostate cancer (mHSPC). METHODS: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014-2020) in the United States of America (USA). We collected demographics, disease characteristics, and laboratory data, including complete blood counts (CBC) at the start of upfront therapy. We evaluated overall survival (OS) and progression-free survival (PFS) associated with baseline lab values. RESULTS: 165 patients were included with a median follow-up time of 33.5 months (mo). 105 (63.6%) had Gleason scores of 8-10 and 108 (65.9%) were classified as high-volume disease. 92 patients received upfront docetaxel (55.8%) and 73 received upfront abiraterone (44.2%). Univariate analyses (UVA) and multivariable analyses (MVA) identified worse clinical outcomes (CO) associated with elevated basophils and basophil-to-lymphocyte ratio (BLR). Based on MVA, elevated basophils (defined as ≥0.1, optimal cut) were associated with a hazard ratio (HR) of 3.51 (95% CI 1.65-7.43, P 0.001) for OS and HR of 1.88 (95% CI 1.05-3.38, P 0.034) for PFS. Our MVA also found that BLR ≥0.0142 was associated with HR 2.11 (95% CI 1.09-4.10, P 0.028) for OS; however, PFS was not statistically significant. CONCLUSION: We conclude that elevated baseline basophils and BLR are associated with worse clinical outcomes in mHSPC. Although results require further validation, BLR is a potential prognostic biomarker.

Clinical Outcomes and Racial Disparities in Metastatic Hormone-Sensitive Prostate Cancer in the Era of Novel Treatment Options.

BACKGROUND: Docetaxel (DOC) and abiraterone (ABI) in the upfront setting have separately improved clinical outcomes for metastatic hormone-sensitive prostate cancer (mHSPC), but there are no studies comparing drug efficacies or the influence of racial disparities. MATERIALS AND METHODS: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014-2020) for patients with mHSPC treated with either upfront DOC or ABI. Outcomes evaluated were overall survival (OS), progression-free survival (PFS), and prostate-specific antigen complete response (PSA CR). RESULTS: A total of 168 patients were included, consisting of 92 (54.8%) Black patients and 76 (45.2%) non-Black patients (69 White and 7 Asian or Hispanic). Ninety-four (56%) received DOC and 74 (44%) received ABI. Median follow-up time was 22.8 months with data last reviewed June 2020. For OS, there was no significant difference between ABI versus DOC and Black versus non-Black patients. For PFS, DOC was associated with hazard ratio (HR) 1.7 compared with ABI for all patients based on univariate association and HR 2.27 compared with ABI for Black patients on multivariable analysis. For PSA CR, Black patients were less likely to have a CR (odds ratio [OR] = 0.27). CONCLUSION: ABI and DOC have similar OS with a trend toward better PFS for ABI in a cohort composed of 54% Black patients. Racial disparities were observed as prolonged PFS for Black patients treated with ABI, more so compared with all patients, and less PSA CR for Black patients. A prospective trial comparing available upfront therapies in a diverse racial population is needed to help guide clinical decision-making in the era of novel treatment options. IMPLICATIONS FOR PRACTICE: Overall survival is similar for abiraterone and docetaxel when used as upfront therapy in metastatic hormone-sensitive prostate cancer in a cohort composed of 54% Black patients. There is a trend towards improved progression-free survival for abiraterone in all patients and Black patients. Non-Black patients were more likely to achieve prostate-specific antigen (PSA) complete response regardless of upfront therapy.

Retrospective study evaluating the safety of administering pegfilgrastim on the final day of 5-fluorouracil continuous intravenous infusion.

BACKGROUND: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor used to prevent neutropenia, is not indicated for administration within 24 h of completion of chemotherapy. The safety of administering pegfilgrastim in gastrointestinal cancer chemotherapy regimens containing continuous intravenous infusion of 5-fluorouracil (5-FUCI) on the day of completion of 5-fluorouracil has not been adequately studied. METHODS: An institutional review board-approved retrospective analysis of patients with a gastrointestinal malignancy receiving pegfilgrastim on the final day of 5-FUCI was conducted. The primary end point was to determine the incidence of grade 3 and grade 4 neutropenia and febrile neutropenia when pegfilgrastim was administered on the final day of 5-FUCI. The secondary endpoint was to determine rate of dose reductions and treatment delays. RESULTS: A total of 300 patients were reviewed from January 2010 to May 2017. The most common cancers were colorectal (25%) and pancreatic (60%), with 77% of patients having late stage disease. The risk of a patient developing grade 3 neutropenia was 0.010 (95% CI 0.002-0.029) and grade 4 neutropenia was 0.007 (95% CI 0.001-0.024). The risk of febrile neutropenia was 0.007 (95% CI 0.001-0.024). The risks of treatment delay and treatment reduction were 0.013 (95% CI 0.004-0.034) and 0.010 (95% CI 0.002-0.029), respectively. CONCLUSION: The low risk of grade 3 and grade 4 neutropenia, febrile neutropenia, as well as dose delays and/or reduction suggests that pegfilgrastim can be administered on the final day of 5-FUCI. Limitations of this study were that it was retrospective in nature and was conducted at a single institution.

Adherence to Oral Anticancer Medications After Implementation of an Ambulatory Adherence Program at a Large Urban Academic Hospital.

PURPOSE: Oral anticancer medications (OAMs) offer convenient administration, reducing the burden of cancer treatment, but create challenges for patients and practitioners. Using data from the Quality Oncology Practice Initiative analysis, a baseline adherence rate of 30% was identified at a large public, academic hospital. To improve OAM adherence, a quality improvement initiative was conducted. METHODS: The aim was to increase OAM patient adherence by 30 percentage points. Through cause-and-effect analysis, adherence barriers were identified, leading to the development of 2 strategies: low-cost adherence tools and a pharmacist-led adherence program. Prescription refill data were collected before and after the intervention, using prescription-fill data and specialty pharmacy records. Adherence was defined as the patient having the drug available at least 80% to less than 120% of the days evaluated for 4 treatment cycles. Other indicators collected included the number of interventions, OAM-related toxicity, emergency room visits, and hospitalizations. RESULTS: OAM adherence increased from 37% to 85% (n = 20 of 54 v 44 of 52 patients; P < .0001) in 1 year. During the study, 655 interventions were documented by the pharmacist (adherence related, n = 331; treatment related, n = 324). The number of oncology-related emergency room referrals leading to hospitalization increased from 52% (n = 13 of 25) to 62% (n = 23 of 37) during the study period. CONCLUSION: A pharmacist-led adherence program, combined with low-cost adherence tools, exceeded the goal for the adherence initiative, suggesting that a multidisciplinary collaborative approach to OAM adherence can have a significant impact on outcomes.

Evaluation of Treatment-Dose Enoxaparin in Acutely Ill Morbidly Obese Patients at an Academic Medical Center: A Randomized Clinical Trial.

BACKGROUND: Enoxaparin dosing recommendations for morbidly obese patients are lacking. Retrospective and observational studies reported goal anti-Xa levels with a median dose of 0.8 mg/kg using total body weight. Further studies are needed to determine if a more conservative dosing strategy is warranted. OBJECTIVE: To determine if reduced dose enoxaparin was more effective than standard dose at achieving goal anti-Xa levels in morbidly obese patients. METHODS: A prospective, randomized, controlled study was conducted in patients with a body mass index (BMI) ≥40 kg/m2. Patients were randomized to standard (1 mg/kg) or reduced dose (0.8 mg/kg) enoxaparin every 12 hours. The primary outcome was the proportion of patients with an initial anti-Xa at goal (0.5-1.1 IU/mL). RESULTS: A total of 62 patients were enrolled and randomized to 1 mg/kg (n = 32) or 0.8 mg/kg (n = 30), and 54 patients completed the study. The study did not meet accrual for 80% power. Goal anti-Xa levels were achieved in a similar proportion for the reduced-dose (n = 25/28) and standard dose arms (n = 20/26; 89.3% vs 76.9%; P = 0.29). Overall, 9 patients required dose adjustments, of which 6 were in the 1-mg/kg arm, and all were above goal. No documented bleeding or thrombotic events were reported. CONCLUSIONS AND RELEVANCE: This was the first randomized, controlled trial of enoxaparin dosing in patients with a BMI ≥40 kg/m2. Overall, 89% of patients had a goal anti-Xa when initiated on 0.8 mg/kg. Based on the results, reduced dose enoxaparin may be a reasonable dosing strategy in morbidly obese patients.

Assessment of Provider Adherence to Recommended Monitoring Parameters for Oral Anticancer Medications.

INTRODUCTION: Oral anticancer medications (OAMs) offer convenient administration but create new challenges with unique toxicity profiles, specific monitoring parameters and non-continuous dosing schedules. We evaluated provider compliance with US Food and Drug Administration (FDA) drug labeling-specified monitoring parameters for commonly dispensed OAMs at a public academic health system. METHODS: A retrospective chart review of patients receiving OAMs was conducted at Grady Health System between July 2015 and June 2016. Patients included in the evaluation were dispensed one of the ten most common OAMs used in our cancer center. Laboratory data and provider documentation were collected and compared to FDA drug labeling-specified monitoring parameters, and the primary outcome was the percentage of fully-compliant cycles. Secondary outcomes included patient adherence assessed by provider documentation and fill history. Descriptive statistics were used to evaluate the data. RESULTS: The initial report comprised 422 patients, of which 77 patients with a total of 349 treatment cycles were included for final analysis. One hundred twenty-six (36.1%) of the treatment cycles were fully compliant with the FDA drug labeling-specified monitoring parameters. Sixty-four of the 199 (32.2%) applicable clinic notes documented patient adherence, and 15 (39.5%) of 38 patients were adherent based on fill history. CONCLUSION: This study revealed low compliance with FDA-recommended monitoring parameters for commonly dispensed OAMs at our institution. In addition, this study confirmed national concerns about adherence to oral regimens. It also suggests that provider compliance with monitoring parameters is an area that needs to be addressed in order to improve the ambulatory OAM process.

Analysis of Opioid Use Following Curative Cancer Treatment at a Large Urban Safety-net Hospital.

OBJECTIVES: This study examined the pattern of use and factors predicting prolonged prescription opioid medications among cancer patients following treatment with curative intent. MATERIALS AND METHODS: Patients diagnosed with cancer over a 3-year period at a large urban safety-net hospital were included. Univariate and multivariate analyses was used to identify factors associated with continued opioid use. RESULTS: Of the 199 patients included in the study, 38% continued to receive an opioid prescription well beyond the acute diagnosis and treatment phase. Mean age was 60.3 years, with a female preponderance (63%). Surgical resection only (31.6%) and the combination of surgery, chemotherapy, and radiation (19.7%) were the commonest treatment modalities. Pain-related comorbidities predating cancer diagnosis were reported in 53.3% of the patients, and about 33% were also on pain-modifying medications (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.92-6.77; Fisher exact test P<0.001). Average number of prescriptions received per patient was 4.8 (range, 1 to 31), over an average of 9.5 months (range, 1.2 to 28.1 mo). Mean morphine milligram equivalents prescribed per prescription was 319 mg (range, 48 to 2475 mg). According to multivariate model, patients who received chemotherapy (OR, 7.25; 95% CI, 2.09-25.17; P=0.0018), or pain-modifying medications (OR, 4.61; 95% CI, 2.25-9.44; P<0.0001) were significantly more likely to continue to receive prescriptions for opioids. DISCUSSION: Treatment with chemotherapy, pain-modifying medications, cancer stage, and interval between diagnosis and treatment are the best predictors for continuous opioid use. The current epidemic of opioid misuse and abuse makes examination current practices and identifification of areas of improvement imperative.

Antibiotic allergies in the medical record: effect on drug selection and assessment of validity.

STUDY OBJECTIVES: To determine the frequency with which reported antibiotic allergies alter drug selection and to assess the validity of these allergies. DESIGN: Retrospective medical record review, with concurrent interviews conducted in a selected subgroup of patients. SETTING: Tertiary care academic medical center. PATIENTS: Three hundred patients with at least one documented antibiotic allergy and who received an antibiotic while hospitalized. MEASUREMENTS AND MAIN RESULTS: Data were collected to determine the patients' allergies documented in the medical record. The first antibiotic regimen that each patient received while hospitalized was evaluated for deviation from the standard of care as determined from institutional protocols, recommendations in the literature, and expert opinion. A total of 416 allergies to antibiotics were reported. Penicillins were the agents most commonly reported (198 reports), followed by sulfonamides, cephalosporins, macrolides, and fluoroquinolones. The reported allergies altered antibiotic therapy in 91 (30.3%) patients. Report of a penicillin or cephalosporin allergy and use of antibiotics for prophylaxis were strong predictors of altered therapy. The subgroup consisted of 100 patients who were interviewed to determine the specific details of their reported allergic reactions. For 22 of the 100 patients, major discrepancies were found between their verbal reports and medical record documentation. The Naranjo adverse drug reaction probability scale was used to determine the validity of their reactions. Among these 100 patients, 109 (78.4%) of 139 reported reactions to antibiotics were deemed to be allergic in nature. For 55 (50.5%) of the 109 allergic reactions, the Naranjo score was 5 or greater, which correlates with probable to definite validity. CONCLUSION: Discrepancies between the medical record and in-depth allergy histories are common, and the validity of reported allergic reactions is frequently questionable. Because documentation of an antibiotic allergy frequently alters therapy, increased effort to verify these reactions may be beneficial.