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Although initially successful, treatments with chemotherapy often fail because of the recurrence of chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response to chemotherapy. However, alternative mechanisms of intrinsic chemoresistance in the chemotherapy-naïve setting may exist but remain poorly understood. Here, we study drug-naïve murine breast cancer brain metastases (BCBMs) to identify how cancer cells growing in a secondary site can acquire intrinsic chemoresistance without cytotoxic agent exposure. We demonstrate that drug-naïve murine breast cancer cells that form cancer lesions in the brain undergo vascular mimicry and concomitantly express the adenosine 5'-triphosphate-binding cassette transporter breast cancer resistance protein (BCRP), a common marker of brain endothelial cells. We reveal that expression of BCRP by the BCBM tumor cells protects them against doxorubicin and topotecan. We conclude that BCRP overexpression can cause intrinsic chemoresistance in cancer cells growing in metastatic sites without prior chemotherapy exposure.

Purpose: Our objective was to determine what vial sharing techniques and other strategies were being used globally to reduce wastage from partially used single-use drug vials, what barriers are preventing these strategies being employed, and what savings are being achieved., Methods: A survey, comprising 19 questions, was distributed to the membership of the International Society of Oncology Pharmacy Practitioners and British Oncology Pharmacy Association. Questions asked included how parenteral cancer drugs are obtained and prepared, what vial sharing strategies are used, what means are employed to extend stability, how prepared products are reused and what cost savings are achieved., Results: In all, 74 responses were received from 20 countries, most from the United Kingdom. Some manufacturing is done by 60.8% of institution, with 41.9% making all products. Vial sharing strategies, for frequently used drugs, were employed in 53% of cases. Barriers preventing vial sharing being used included government legislation, USP 797 guidelines, and health insurance companies. Extension of stability was possible for 70.2% of centres. Most respondents reported reduction in cytotoxic and biological waste, and alleviation of drug shortages from vial sharing utilisation. Cost savings were achieved in 74% of cases and was significant in one third., Conclusions: The survey has determined that drug vial wastage and expenditure can be reduced, and vial sharing facilitates this. International collaboration plus the assistance of governments and the pharmaceutical industry is vital in achieving this aim. These findings can hopefully guide oncology pharmacy in establishing appropriate strategies to reduce wastage internationally.

Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial-to-mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro- or antitumorigenic. In this review, we will focus on recent evidence regarding therapy-induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Medication errors involving look alike sound alike (LASA) medications have widely been recognized to contribute to patient harm. Oncology biosimilars are considered to be LASA medications and require additional measures for operational safety. The Cancer Care Alberta (CCA) Pharmacy Educators developed an education strategy to ensure operational and patient safety during the implementation phase for oncology biosimilars in Alberta, Canada. This resulted in a smooth adoption of oncology biosimilars. As future oncology biosimilars are introduced, this framework will serve as the foundation to educate and train oncology pharmacy staff.

Chemotherapy checking is a complex task and requires a high level of alertness and attention to detail. Learning tools are required to teach the fundamental principles of chemotherapy checking. In conjunction with a graphic design team and with input from Human Factors specialists, an online chemotherapy checking training module was created. A variety of learning methods were incorporated including pre-reading, hands on training, case scenarios, and exam questions. The necessary skills to safely complete chemotherapy checking can be enhanced by the use of this training module.

Increasingly stringent pharmacy standards for preparation of sterile products necessitated a review of the feasibility of continuing to maintain chemotherapy sterile production facilities across the provincial cancer programme. The concept of centrally produced chemotherapy that could be shipped to various locations as a remote service delivery model was explored. Key planning principles were established and detailed processes were developed to test this change in service delivery at one small cancer centre. Following the successful implementation and evaluation of the remote service delivery model at one centre, the programme was rolled out to an additional four centres.

Aim: To identify cancer drugs amenable to strategies for reducing expenditure and avoiding drug wastage., Methods: Information was sourced from product information in 20 countries on parenteral cytotoxic agents, and cancer and noncancer monoclonal antibodies. Data were collected on vial sizes, overage, stability and presentation forms., Results: Vial size availability varied significantly between countries, with often only single vial sizes for numerous medications. Overage was poorly reported. Stability data were inconsistent and variable between countries, with most drugs only having a 24 h expiry. Three cancer-indicated monoclonal antibodies, thought suitable for prefilled syringe administration, were only available as vials., Conclusion: Many expensive cancer drugs are suitable for global cost-reduction strategies. Collaboration is vital to affecting change and reducing expenditure.

Background: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS., Methods: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes., Results: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005)., Conclusions: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Following a review of a chemotherapy medication adverse event where the incorrect medication was prepared by a pharmacy, a number of steps were taken to review the literature and best practice information related to checking processes for the preparation of parenteral chemotherapy. Concepts such as identification of critical stop check points, independent double checks, and human factors principles were reviewed and incorporated into newly designed chemotherapy preparation worksheets with embedded checklists. Usability testing and staff feedback during implementation revealed a number of key learning points that resulted in additional work to further improve the chemotherapy worksheets with embedded checklists and highlighted the need for a culture of continuous quality improvement., (© The Author(s) 2014.)

Introduction: Chemotherapy-induced nausea and vomiting (CINV) has been shown to adversely impact patient anxiety, quality of life, treatment adherence, and use of health care resources. CINV control still remains a challenge, and lack of effective communication between the patient and clinician has been highlighted in the literature as the main barrier to optimal control. The Multinational Association of Supportive Care in Cancer (MASCC) has developed a tool (MASCC Antiemesis Tool (MAT)) to improve assessment and subsequent management of CINV by enhancing communication between patients and their clinicians. This study assessed the feasibility of using the MAT in patients at the Tom Baker Cancer Centre. The secondary objective was to describe the incidence of CINV as identified by the tool., Methods and Materials: This study involved a prospective survey using the MAT in patients receiving intravenous chemotherapy. Subjects completed the MAT twice post-chemotherapy regarding CINV symptoms and returned it at their next clinic appointment. Participants were also surveyed to evaluate feasibility with regard to using the MAT., Results: Of the 50 patients recruited, 56% returned surveys. The majority of patients reported that the MAT facilitated communication with their clinician, particularly those who had experienced CINV. Fifty-four percent of patients who returned the MAT reported CINV; however, less than half of them had received American Society of Clinical Oncology-recommended antiemetic regimens. Only four patients with CINV had antiemetic changes made for subsequent cycles., Conclusion: The MAT is a feasible tool which can improve communication of CINV symptoms between patients and clinicians, a foundational step toward improving CINV management., (© The Author(s) 2014.)

Background: Oral tyrosine kinase inhibitors are the standard of care for chronic myeloid leukemia. Tyrosine kinase inhibitors are administered in an outpatient setting for an indefinite period which may negatively impact adherence. Non-adherence to tyrosine kinase inhibitors is associated with disease progression., Objectives: To evaluate the need for adherence-enhancing interventions, this study was designed to determine the proportion of chronic myeloid leukemia patients non-adherent to their tyrosine kinase inhibitor regimen. The secondary objective was to identify the influence of patient characteristics on tyrosine kinase inhibitor adherence., Methods: Cross-sectional retrospective chart and dispensing record reviews were performed to identify patients receiving a tyrosine kinase inhibitor from 1 June 2010 to 31 January 2012. Adherence was evaluated using the medication possession ratio., Results: A total of 124 patients were included. Thirty-eight (31%) patients were non-adherent to their tyrosine kinase inhibitor regimen. Patients not receiving concurrent medications were more likely to be non-adherent (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.05-5.13, p=0.04). The median medication possession ratio was 0.95 (IQR=0.83-1.07). Median medication possession ratio was lower in patients receiving imatinib compared to dasatinib or nilotinib (0.95 vs. 1.00, p=0.01) and in those less than 50 years old compared to those greater than 50 years old (0.92 vs. 0.97, p=0.02)., Conclusions: Optimal tyrosine kinase inhibitor adherence in chronic myeloid leukemia patients poses a significant obstacle in achieving best possible outcomes while reducing healthcare costs. In this study, one in three chronic myeloid leukemia patients treated with a tyrosine kinase inhibitor were non-adherent to their regimen. Those at higher risk of non-adherence were on no concurrent medications, less than 50 years old, and those treated with imatinib. Active intervention to improve tyrosine kinase inhibitor adherence should be developed, implemented, and evaluated to improve patient outcomes at our center., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: A randomized trial carried out by Shepherd et al. in patients with advanced or metastatic non-small-cell lung cancer showed statistically significant benefit of erlotinib over placebo in prolonging overall survival and progression-free survival., Objectives: The primary outcome was to compare overall survival of patients treated with erlotinib for non-small-cell lung cancer at Alberta Health Services - Cancer Care to the overall survival seen in the pivotal trial. Secondary outcomes included comparing progression-free survival, overall response rate, and duration of response between the two patient populations., Methods: A retrospective review of charts was conducted for patients with locally advanced or metastatic non-small-cell lung cancer who received erlotinib therapy after failure of at least one prior chemotherapy regimen between 1 August 2006 and 31 July 2009. Survival data was analyzed using the Kaplan-Meier method., Results: Median overall survival and progression-free survival were 5.19 months and 2.46 months, respectively, in Alberta Health Services - Cancer Care patients. The rate of response was 11% (median duration of response, 6.7 months). The likelihood of a response to erlotinib was higher among nonsmokers (p < 0.0001) and those with response to prior chemotherapy (p = 0.0896). In multivariate analysis, good performance status (p = 0.0109) and response to prior therapy (p < 0.0001) were favorable factors for survival., Conclusions: In a clinical setting, erlotinib does not perform as well in terms of median overall survival as reported in the pivotal trial (5.19 vs. 6.70 months).

Objective: To continue with workplace contamination monitoring in the Alberta Cancer Board (ACB) pharmacy practice environment., Setting: The ACB in the Canadian province of Alberta which includes two public tertiary centers and 19 associated community satellite sites based around the province in existing hospitals., Methods: After the completion of a Phase 1 and Phase 11 study,(1) which investigated the feasibility of routine monitoring of antineoplastic agent contamination in the pharmacy practice environment, it was decided to launch a Phase III study. The Phase III study would be done at the Cross Cancer Institute in the main pharmacy department as well as at a brand new satellite pharmacy within the CCI hospital. Samples would be taken in these areas as well as on the outer exterior of latex gloves worn to prepare cyclophosphamide and other antineoplastics., Results: The result determined that the area in front of the biological safety cabinet in the main CCI pharmacy department as well as the exterior of the latex gloves showed evidence of cyclophosphamide contamination. The results from the sample taken in the new satellite pharmacy showed no evidence of cyclophosphamide contamination., Conclusion: results from this study prompted a decision to launch a Phase IV study to determine the feasibility within our network, for routine monitoring as well as sampling throughout the clean room beyond the BSC.

Background: The safe use of medications is a major concern in oncology practice. Three organizations collaborated on a survey to determine if practitioners had implemented current recommended safe practices for IV vincristine administration, general oncology safe practices, and safe practices for oral chemotherapy., Methods: A survey was distributed to members of the Hematology Oncology Pharmacy Association (HOPA) and the International Society of Pharmacy Practitioners (ISOPP) using Survey Monkey. The Institute of Safe Medication Practices (ISMP) also solicited readers of its Medication Safety Alert! to respond to the survey. A comparison to results from a survey conducted by ISMP in 2006 on safe practices for IV vincristine was also conducted., Results: The majority of respondents were aware of the WHO recommendations for IV vincristine, although the rate of implementation of the guidelines ranged from 24.1 to 53.6%. When compared to the ISMP 2006 survey there was a 25.8-37.4% improvement in following many of the safe practice guidelines. Administering IV vincristine via a minibag showed the lowest rate of adoption (less than 40%). Of the 35 survey items on general chemotherapy safety strategies, 80% of respondents had implemented at least 21 items in the survey. Overall 32.4% of respondents did not consider oral chemotherapy as requiring the same safety concerns as parenteral therapy., Conclusions: The results of this survey will provide a new baseline for the adoption rate of safe medication practice recommendations related to oncology. Further work on addressing barriers in adopting identified safe practice recommendations needs to be conducted.

Study Objective: To investigate the feasibility of routine monitoring for workplace antineoplastic agent contamination in the Alberta Cancer Board (ACB) pharmacy practice environment., Setting: The ACB in the Canadian province of Alberta, which includes two public tertiary centres and 17 associated community satellite sites based around the province in existing hospitals., Methods: Obtained organizational support and input prior to launching the feasibility study (Phase I). Samples were analysed for a common cytotoxic agent - cyclophosphamide. Surfaces chosen were within the biological safety cabinets, workplace counter tops and on external surfaces of vials provided by manufacturers. Blank samples and known contaminated controls were included in Phase I to reconfirm the methodology in a previously published study. Feasibility aspects of logistics and financial expenses were examined. A second phase (Phase II) was completed to test other areas of the pharmacy and vials, with blank samples included to reconfirm previously mentioned methodology., Results: The results determined that the samples tested were below acceptable detection limits with the exception of the known contaminated sample (Phase I) and exterior surfaces of vials (Phase II)., Conclusion: This project has increased staff awareness of the sources for antineoplastic agent workplace contamination. Some practice changes were instituted during the project itself. Logistics and expenses were realistic for routine monitoring to be adopted.