Women in oncology pharmacy leadership: A white paper.

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.

Corticosteroids for the management of immune-related adverse events in patients receiving checkpoint inhibitors.

INTRODUCTION: Due to enhanced T-cell activity, immune checkpoint inhibitors cause immune-related adverse effects. Corticosteroids are the mainstay of immune-related adverse effect management but the optimal strategy has not been determined, putting patients at risk for steroid-related adverse effects and potentially decreased efficacy of immunotherapy. This study aims to characterize the use of corticosteroids for the management of immune-related adverse effect. METHODS AND MATERIALS: A retrospective, single-center evaluation of patients receiving checkpoint inhibitors was conducted. The primary objective was to evaluate corticosteroid use for immune-related adverse effects, including starting dose, taper strategy, total duration, and resumption of immunotherapy. Secondary objective was to describe the incidence and significance of hyperglycemia. RESULTS: One hundred and three patients met inclusion criteria and experienced 123 immune-related adverse effects. Prednisone was used most commonly (67%) at an average starting dose of 0.88 mg/kg (range 0.07-17.0). On average, steroid tapers began 9.2 days after initiation (range 0-89) and were continued for a total of 84.2 days (range 3-693). In 21.1% of cases, checkpoint inhibitor therapy was not delayed and 68.6% resumed checkpoint inhibitors, while the patient was taking steroids (30.4 mg prednisone on average, range 5-80). On average, checkpoint inhibitor therapy was resumed 18.6 days after detection of immune-related adverse effect (range 0-150). Clinically relevant hyperglycemia occurred in 8.9%. CONCLUSION: Utilization of steroids for immune-related adverse effect at our institution is highly variable. The majority of patients received prolonged courses of steroids and resumed checkpoint inhibitor therapy with concomitant steroids above recommended doses. Additional monitoring for hyperglycemia and other steroid associated adverse effects should be considered.

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893.

BACKGROUND: The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data. PROCEDURES: Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide. Vinblastine and celecoxib were concomitantly administered. Surgical, radiotherapeutic, or combination local control therapy was given per institutional preference. RESULTS: Thirty-five eligible patients were enrolled. Ninety percent received at least 75% of planned vinblastine/celecoxib doses. There was no excess of neurologic, infectious, hemorrhagic, or cardiovascular toxicities. However, 7 of 21 patients who received pulmonary irradiation prior to experiencing pulmonary toxicity did develop grade 2 or greater pulmonary toxicity, including two deaths of apparent radiation pneumonitis. Fourteen of 16 patients with pelvic disease received local irradiation. Hemorrhagic cystitis developed in six patients, five of whom had received pelvic irradiation. The overall 24-month event free survival was 35% (19-51%); 71% (26-92%) for the seven with isolated pulmonary metastases, 26% (10-45%) for all others. CONCLUSION: The combination of vinblastine/celecoxib metronomic therapy with standard ES treatment was feasible according to the protocol definitions. However, excess toxicity in irradiated areas was noted and limits the usefulness of this protocol. The 24-month EFS for those with isolated pulmonary metastases is better than historical controls, although the number of patient number is small, follow up short and we are lacking contemporaneous controls.

Effectiveness of exogenous albumin administration for the prevention of ifosfamide-induced encephalopathy.

STUDY OBJECTIVES: To assess the effectiveness of prophylactic albumin for the prevention of ifosfamide-induced encephalopathy (IIE), and to describe risk factors for IIE and investigate the predictive potential of a novel risk-stratification model for IIE. DESIGN: Retrospective analysis. SETTING: Single academic medical center. PATIENTS: Forty-one adults who received 93 chemotherapy cycles of regimens that included ifosfamide for the treatment of hematologic or solid tumor malignancy between November 2007 and November 2008. Patients were divided into two groups based on the use of albumin for IIE prophylaxis: albumin group (32 cycles) and no albumin group (61 cycles). MEASUREMENTS AND MAIN RESULTS: Overall occurrence of neurotoxicity during therapy served as the primary outcome measure. Proposed risk factors for IIE were assessed by conducting a subgroup analysis of patients who did and those who did not experience IIE. A novel risk-stratification model was developed in an attempt to predict patients at risk for IIE. The validity of the scheme was assessed by comparing the occurrence of IIE among high- and low-risk patients as identified by the model. Overall, among the 93 cycles, six cases of IIE (6.5%) were identified. The occurrence of IIE was more common in the albumin group compared with the no albumin group (15.6% [5/32] vs 1.6% [1/61], p=0.01). Baseline albumin level was significantly lower, and serum creatinine and aspartate and alanine aminotransferase concentrations were significantly higher among patients experiencing IIE. All cases of IIE occurred among patients identified as high risk according to the risk-stratification model (p=0.01). CONCLUSION: Prophylactic therapy with exogenous albumin is not an effective strategy for the prevention of IIE. The novel risk-stratification model appears to be an effective method for predicting patients with the greatest potential for developing this adverse effect.

Obesity and outcome in pediatric acute lymphoblastic leukemia.

PURPOSE: To evaluate the effect of obesity (defined as a body mass index > 95th percentile for age and sex at diagnosis) on outcome of pediatric acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We retrospectively analyzed data from 4,260 patients with newly diagnosed ALL enrolled from 1988 to 1995 onto five concurrent Children's Cancer Group studies. Results were verified in a second cohort of 1,733 patients enrolled onto a sixth study from 1996 to 2002. RESULTS: The 1988 to 1995 cohort included 343 obese and 3,971 nonobese patients. The 5-year event-free survival rate and risk of relapse in obese versus nonobese patients were 72% +/- 2.4% v 77% +/- 0.6% (P = .02) and 26 +/- 2.4 v 20 +/- 0.6 (P = .02), respectively. After adjusting for other prognostic variables, obesity's hazard ratios (HRs) of events and relapses were 1.36 (95% CI, 1.04 to 1.77; P = .021) and 1.29 (95% CI, 1.02 to 1.56; P = .04), respectively. The effect of obesity was prominent in the 1,003 patients > or = 10 years old at diagnosis; in this subset, obesity's adjusted HRs of events and relapses were 1.5 (95% CI, 1.1 to 2.1; P = .009) and 1.5 (95% CI, 1.2 to 2.1; P = .013), respectively. In a second cohort of 1,160 patients 10 years old, obesity's adjusted HRs of events and relapses were 1.42 (95% CI, 1.03 to 1.96; P = .032) and 1.65 (95% CI, 1.13 to 2.41; P = .009), respectively. The effect of obesity on outcome was unrelated to changes in chemotherapy doses, length of intervals between chemotherapy cycles, or incidence and severity of therapy-related toxicity. CONCLUSION: Obesity at diagnosis independently predicts likelihood of relapse and cure in preteenagers and adolescents with ALL.

Obesity in pediatric oncology.

Today's obesity pandemic began in the United States, spread to Western Europe and other developed regions, and is emerging in developing countries. Its influences on outcomes of childhood cancer are unknown. A recent Children's Oncology Group symposium considered epidemiology of obesity, pharmacology of chemotherapy and outcomes in obese adults with cancer, excess mortality in obese pediatric patients with acute myeloid leukemia (AML), and complications in obese survivors. The salient points are summarized herein. Body mass index (BMI) is the accepted index of weight for height and age. In the US, obesity prevalence (BMI > 95th centile) is increasing in all pediatric age groups and accelerating fastest among black and Hispanic adolescents. Pharmacologic investigations are few and limited: half-life, volume of distribution, and clearance in obese patients vary between drugs. Obese adults with solid tumors generally experience less toxicity, suggesting underdosing. For patients undergoing bone marrow transplantation, obese adults generally experience greater toxicity. In pediatric acute myeloblastic leukemia, obese patients have greater treatment-related mortality (TRM), similar toxicity and relapse rates, and inferior survival compared with patients who are not obese. An excess of female survivors of childhood leukemia who received cranial irradiation are obese. Ongoing treatment effects of childhood cancer may predispose to a sedentary lifestyle. These findings call for measures to prevent obesity, retrospective and prospective studies of chemotherapy pharmacology of analyzed according to BMI and outcomes, additional studies of the obesity impact on outcomes in pediatric cancer, and promotion of a healthy lifestyle among survivors.