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PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild-Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild-Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23-89/34-74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle-1 (96%), average 5-7 days from sample collection. PGx-dosing for DPYD variant allele carriers reduced high-grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01-0.97, p = 0.024). High-grade toxicities among Wild-Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64-1.54, p = 0.490). PGx-dosing reduced FP-related hospitalizations (-22%) and deaths (-3.7%) compared to controls. There were no high-grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Regulatory pathways adopted by the United States Food Drug and Administration (FDA) and Australian Therapeutic Goods Administration (TGA) enable expedited approval of medicines that are thought to offer significant clinical advantage over existing options for severe diseases., Objectives: To review Australian accessibility to medicines approved through the FDA breakthrough therapy designation (BTD) process including timelines and approvals by the TGA and Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the Pharmaceutical Benefits Scheme (PBS)., Methods: Retrospective review of published reports from the FDA, TGA, PBAC and PBS for BTDs from 1 January 2013-31 August 2023. Uniform data about BTD and milestone dates were collected. Analysis included all BTDs approved by FDA until 31-August-2022. Main outcome measures: Rates of approval by TGA and PBAC, and PBS-listing; and median (interquartile range, IQR) time from FDA submission to FDA approval, and FDA approval to TGA approval, PBAC approval and PBS listing for cancer and non-cancer medicines., Results: Of 237 BTDs across 156 medicines, 68% were approved by the TGA, and 37% were listed on the PBS. Median (IQR) time from FDA submission to FDA approval was shorter for cancer compared to non-cancer; 179 days (140-210) vs 232 days (181-245), p  < 0.02. Time from FDA approval to PBS listing was similar for cancer and non-cancer; median 744 days (IQR, 549-1136) and 733 days (IQR 440-960) respectively, with improvements for cancer BTDs noted for 2018-2022 compared to 2013-2017; 566 days (IQR 319-831) vs 880 days (IQR 620-1362), p  < 0.02 but not for non-cancer BTDs., Conclusion: BTD medicines are accessible in Australia approximately 2 years after FDA approval. Since 2018, time to PBS listing for cancer therapies improved, mirroring shorter FDA approval times for this category. Further understanding of clinical studies and context by therapeutic area may improve timely and safe access to life-saving medicines., Competing Interests: SL is the secretary of the Pharmacy & Therapeutics Advisory Committee at the Peter MacCallum Cancer Centre and has oversight of the hospital medicines formulary. JZ holds leadership positions in ICON Group and Lipotek; has pecuniary interests in Biomarin, Ophthea, Amarin, Frequency Therapeutics, Gilead, UniQure, Orphazyme and Moderna Therapeutics; is on Advisory Boards for Merck Sharp & Dohme, Specialized Therapeutics, Deciphera, Revolution Medicine, FivePHusion, Genorbio, 1Global, Novotech and Alloplex Biotherapeutics Inc; and has received research funding from Bristol-Myers Squibb, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology, Servier and Astellas Pharma. All other authors declare no conflicts of interest., (© 2024 Peter MacCallum Cancer Centre. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: 30-day mortality after systemic anti-cancer therapy (SACT) has been suggested as a quality indicator primarily for measuring use of chemotherapy towards the end of life. Utility across different cancer types is unclear, especially when using immunotherapy and targeted therapies., Methods: This retrospective study included patients with a diagnosis of lung cancer who received palliative-intent SACT at an Australian metropolitan cancer center between 2015 and 2022. Using a prospectively maintained lung cancer database, patient, disease, and treatment characteristics were evaluated against annual 30-day mortality rates following SACT., Results: 1072 patients were identified. Annual 30-day mortality rate after palliative-intent SACT for lung cancer ranged between 9% and 15%, with significant variance between treatment types. Calculated rates of 30-day mortality are higher if longer reporting time periods are used. Patients who died within 30 days of SACT were more likely to have received targeted therapies or immunotherapy as their final line of treatment, have a poorer performance status at diagnosis, and have received multiple lines of treatment., Conclusions: Our data support differential interpretation of 30-day mortality for quality assurance, especially with regard to lung cancer. Consistency in population and reporting time periods, and accounting for treatment type is crucial if 30-day mortality is to be utilized as cancer care performance quality indicator. Relevance to quality care is questionable in the lung cancer setting., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Investigation of infection risk with subcutaneous versus intravenous trastuzumab and rituximab administration in an individual patient data (IPD) and published data meta-analysis of randomised controlled trials (RCTs)., Methods: Databases were searched to September 2021. Primary outcomes were serious and high-grade infection. Relative-risk (RR) and 95% confidence intervals (95%CI) were calculated using random-effects models., Results: IPD meta-analysis (6 RCTs, 2971 participants, 2320 infections) demonstrated higher infection incidence with subcutaneous versus intravenous administration, without reaching statistical significance (serious: 12.2% versus 9.3%, RR 1.28, 95%CI 0.93to1.77, P = 0.13; high-grade: 12.2% versus 9.9%, RR 1.32, 95%CI 0.98to1.77, P = 0.07). With exclusion of an outlying study in post-hoc analysis, increased risks were statistically significant (serious: 13.1% versus 8.4%, RR 1.53, 95%CI 1.14to2.06, P = 0.01; high-grade: 13.2% versus 9.3%, RR 1.56, 95%CI 1.16to2.11, P < 0.01). Published data meta-analysis (8 RCTs, 3745 participants, 648 infections) demonstrated higher incidence of serious (HR 1.31, 95%CI 1.02to1.68, P = 0.04) and high-grade (HR 1.52, 95%CI 1.17to1.98, P < 0.01) infection with subcutaneous versus intravenous administration., Conclusions: Results suggest increased infection risk with subcutaneous versus intravenous administration, although IPD findings are sensitive to exclusion of one trial with inconsistent results and identified risk-of-bias. Ongoing trials may confirm findings. Clinical surveillance should be considered when switching to subcutaneous administration. PROSPERO registration CRD42020221866/CRD42020125376., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta-analysis aim to evaluate the safety outcomes of reported PGx-guided strategies (Analysis 1) and identify well-studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to January 2023 for clinical trials or comparative studies evaluating PGx strategies or unconfirmed pharmacogenomic variants. The primary outcomes were severe adverse events (SAE; ≥ grade 3) or symptom burden with pain and vomiting as defined by trial protocols and assessed by trial investigators. We calculated pooled overall relative risk (RR) and 95% confidence interval (95%CI) using random effects models. PROSPERO, registration number CRD42023421277. Of 6811 records screened, six studies were included for Analysis 1, 55 studies for Analysis 2. Meta-analysis 1 (five trials, 1892 participants) showed a lower absolute incidence of SAEs with PGx-guided strategies compared to usual therapy, 16.1% versus 34.0% (RR = 0.72, 95%CI 0.57-0.91, p = 0.006, I 2  = 34%). Meta-analyses 2 identified nine medicine(class)-variant pairs of interest across the TYMS, ABCB1, UGT1A1, HLA-DRB1, and OPRM1 genes. Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine-variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti-cancer and supportive care medicine safety and efficacy., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians' views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation., Methods: A study-specific 17-question survey was emailed (01 February-12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics., Results: Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation., Conclusion: PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians' hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

This study explored the acceptability of a novel pharmacist-led pharmacogenetics (PGx) screening program among patients with cancer and healthcare professionals (HCPs) taking part in a multicenter clinical trial of PGx testing (PACIFIC-PGx ANZCTR:12621000251820). Medical oncologists, oncology pharmacists, and patients with cancer from across four sites (metropolitan/regional), took part in an observational, cross-sectional survey. Participants were recruited from the multicenter trial. Two study-specific surveys were developed to inform implementation strategies for scaled and sustainable translation into routine clinical care: one consisting of 21 questions targeting HCPs and one consisting of 17 questions targeting patients. Responses were collected from 24 HCPs and 288 patients. The 5-to-7-day PGx results turnaround time was acceptable to HCP (100%) and patients (69%). Most HCPs (92%) indicated that it was appropriate for the PGx clinical pharmacist to provide results to patients. Patients reported equal preference for receiving PGx results from a doctor/pharmacist. Patients and HCPs highly rated the pharmacist-led PGx service. HCPs were overall accepting of the program, with the majority (96%) willing to offer PGx testing to their patients beyond the trial. HCPs identified that lack of financial reimbursements (62%) and lack of infrastructure (38%) were the main reasons likely to prevent/slow the implementation of PGx screening program into routine clinical care. Survey data have shown overall acceptability from patients and HCPs participating in the PGx Program. Barriers to implementation of PGx testing in routine care have been identified, providing opportunity to develop targeted implementation strategies for scaled translation into routine practice., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type)., Methods: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life)., Results: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27-0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24-0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93-1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66-2.44], p = 0.47)., Conclusion: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response., Registration Number: The study is registered with PROSPERO, registration number CRD42020223768., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Patient understanding of medicines information and adherence to medication instructions are important variables for ensuring optimal cancer care. This randomised controlled trial (RCT) aimed to evaluate the impact of an outpatient clinical pharmacy service on medication adherence and symptom burden in cancer patients., Methods: In this single-centre RCT, 115 patients were randomised 1:1 to a pharmacist-led pharmaceutical care program (intervention, n = 59) versus standard of care (control, n = 56) within an outpatient multidisciplinary radiotherapy clinic. The primary endpoint was medication adherence as assessed by Medication Understanding and Use Self-Efficacy (MUSE) scale and Teach-Back assessment. Secondary endpoints were patient-reported symptom burden assessed by the Edmonton Symptom Assessment Scale (ESAS). Patients were assessed at baseline (weeks 1-2) and at discharge from radiotherapy (weeks 5-7)., Results: Polypharmacy (use of five or more medications) was observed in 26% of patients at baseline compared to 97% at discharge. Patient self-efficacy and medication adherence was higher in the intervention arm compared to the control arm, with a mean MUSE score difference of 2.70 (95% CI 1.24, 4.17) after adjustment for baseline, and a higher proportion of patients with average Teach-Back score of four or more (86% vs 14%; odds ratio (OR) 46.09, 95% CI 14.49, 146.56). The mean (SD) scores for aggregate ESAS (0-100) at discharge were 26.2 (14.0) in the intervention arm and 32.0 (15.8) in the control arm demonstrating lower overall symptom burden associated with the intervention (mean score difference adjusted for baseline - 0.52; 95% CI - 1.03, - 0.01)., Conclusion: A structured outpatient clinic pharmacy service significantly improved medication adherence and reduced overall symptom burden in patients receiving radiotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients receiving radiotherapy for the treatment of cancer can have complex medication requirements related to the management of side-effects and impaired swallowing ability. This study surveyed patients and clinicians to identify service gaps and unmet medication management needs., Methods: Patient and clinician surveys were developed by a multidisciplinary team based on previously validated questionnaires. The patient survey focused on medication use and adherence. The clinician survey was based around a clinical case study and focused on identifying service gaps and practice variations. This survey was disseminated to radiation oncologists, pharmacists and nurses involved with the care of head and neck or lung cancer patients in Victoria., Results: A total of 93 surveys were completed including 53 patient surveys and 40 clinician surveys. Radiotherapy patients reported high medication usage with up to 53% taking five or more medications daily. When asked the same set of questions relating to medication education requirements, patients receiving polypharmacy reported greater needs (72%) than recognised by the surveyed multidisciplinary clinician group (58%). They also reported a non-adherence rate of 46%. In addition, further disparities were identified in clinician practices and their approach to clinical situations which may result in conflicting advice and confusion for patients., Conclusion: While recognising deficiencies relating to the provision of medication information, oncologists, nurses and pharmacists underestimated patient needs for medication information, education and follow-up. Findings support the rationale for integration of pharmacy services within the radiotherapy clinics to support patient care and bridge service gaps relating to medication management.

Background: Patients receiving anticancer therapies are frequently prescribed complex and high-risk medication regimens, which at times can result in medication misadventures. The objective of this review was to assess the effect of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies, including patients undergoing radiotherapy., Methods: A systematic review of original publications indexed in EMBASE, MEDLINE and Cochrane Library from June 2007 to June 2017. Eligible studies evaluated outpatient pharmacy clinic services for cancer patients and reported at least one medication-related quantitative outcome measure. Two authors independently reviewed full-text articles for inclusion, then extracted data and performed quality and risk of bias assessments., Results: Of 908 identified publications, 13 met predefined eligibility criteria; 1 randomised control trial, 2 controlled cohort studies and 10 uncontrolled before-after studies. Many excluded studies described outpatient pharmacy services but lacked medication-related outcomes. All included studies had informative practice model designs, with interventions for drug-related problems including drug dose optimisation ( n = 8), reduced drug interaction ( n = 6) and adverse drug reaction reporting ( n = 3). Most studies ( n = 11) reported on symptom improvement, commonly nausea ( n = 7) and pain ( n = 5). Of four studies in radiotherapy cohorts, pharmacist involvement was associated with improved symptoms, satisfaction and wellbeing scores., Conclusion: Few studies have objectively assessed outpatient pharmacy cancer services, even fewer in the radiotherapy settings. Although the results support these services, significant heterogeneity and bias in the study designs prohibit robust conclusions and further controlled trials are required.

Infection and sepsis are common problems in cancer management affecting up to 45% of patients and are associated with significant morbidity, mortality and healthcare utilisation., Objective: To develop and implement a whole of hospital clinical pathway for the management of sepsis (SP) in a specialised cancer hospital and to measure the impact on patient outcomes and healthcare utilisation., Methods: A multidisciplinary sepsis working party was established. Process mapping of practices for recognition and management of sepsis was undertaken across all clinical areas. A clinical pathway document that supported nurse-initiated sepsis care, prompt antibiotic and fluid resuscitation was implemented. Process and outcome measures for patients with sepsis were collected preimplementation (April-December 2012), postimplementation cohorts (April-December 2013), and from January to December 2014., Results: 323 patients were evaluated (111 preimplementation, 212 postimplementation). More patients with sepsis had lactate measured (75.0% vs 17.2%) and appropriate first dose antibiotic (90.1% vs 76.1%) (all p<0.05). Time to antibiotics was halved (55 vs 110 min, p<0.05). Patients with sepsis had lower rates of intensive care unit admission (17.1% vs 35.5%), postsepsis length of stay (7.5 vs 9.9 days), and sepsis-related mortality (5.0% vs 16.2%) (all p<0.05). Mean total hospital admission costs were lower in the SP cohort, with a significant difference in admission costs between historical and SP non-surgical groups of $A8363 (95% CI 81.02 to 16645.32, p=0.048) per patient on the pathway. A second cohort of 449 patients with sepsis from January to December 2014 demonstrated sustained improvement., Conclusions: The SP was associated with significant improvement in patient outcomes and reduced costs. The SP has been sustained since 2013, and has been successfully implemented in another hospital with further implementations underway in Victoria., Competing Interests: Competing interests: None declared.

Introduction: There is a paucity of data available to assess the occupational health and safety risk associated with exposure to monoclonal antibodies. Industry standards and published guidelines are conflicting or outdated. Guidelines offer contrary recommendations based on an array of methodological approaches. This survey aimed to describe current practices, beliefs and attitudes relating to the handling of monoclonal antibodies by Australian medical, nursing and pharmacy clinicians., Methods: An electronic survey was distributed between June and September 2013. Respondents were surveyed on three focus areas: institutional guideline availability and content, current practices and attitudes. Demographic data relating to respondent and primary place of practice were also collected., Results: A total of 222 clinicians completed the survey, with representation from all targeted professional groups and from a variety of geographic locations. 92% of respondents reported that their institution prepared or administered monoclonal antibodies, with 87% specifically handling anti-cancer monoclonal antibodies. Monoclonal antibodies were mostly prepared onsite (84-90%) and mostly within pharmacy clean-rooms (75%) and using cytotoxic cabinets (61%). 43% of respondents reported access to institutional monoclonal antibody handling guidelines with risk reduction strategies including training and education (71%), spill and waste management (71%), procedures for transportation (57%) and restricted handling (50%). Nurses had a stronger preference towards pharmacy manufacturing than both doctors and pharmacists for a range of clinical scenarios. 95% of all respondents identified that professional or regulatory body guidelines are an important resource when considering handling practices., Conclusion: Monoclonal antibodies are most commonly handled according to cytotoxic drug standards and often in the absence of formal guidelines., (© The Author(s) 2014.)

These consensus guidelines provide recommendations for the safe handling of monoclonal antibodies. Definitive recommendations are given for the minimum safe handling requirements to protect healthcare personnel. The seven recommendations cover: (i) appropriate determinants for evaluating occupational exposure risk; (ii) occupational risk level compared with other hazardous and non-hazardous drugs; (iii) stratification of risk based on healthcare personnel factors; (iv) waste products; (v) interventions and safeguards; (vi) operational and clinical factors and (vii) handling recommendations. The seventh recommendation includes a risk assessment model and flow chart for institutions to consider and evaluate clinical and operational factors unique to individual healthcare services. These guidelines specifically evaluated monoclonal antibodies used in the Australian cancer clinical practice setting; however, the principles may be applicable to monoclonal antibodies used in non-cancer settings. The guidelines are only applicable to parenterally administered agents., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Background: Data suggests that males experience less toxicity and poorer survival than females treated for Ewing's sarcoma. We instituted an intra-patient dose escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC) alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and report its feasibility and safety., Methods: A retrospective review of adherence to DE guidelines and toxicities was conducted for patients who received DE with VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC) was collected on days 8, 12 and 15 for cycles 1-6. DE of 10%/cycle was applied if ANC > 1.5×109/L and platelet > 100×109/L on all blood results. The primary endpoint was the proportion of patients who received appropriate DE. The secondary endpoint was to assess morbidity, changes in hematologic nadirs between gender and age and a comparison with a prior cohort of ESFT patients who did not receive DE. Gender comparisons were assessed via independent 2-sample t-tests assuming unequal variances. Within cycle changes in hematologic nadirs were assessed using repeated measures ANOVA. Relapse free survival and overall survival (OS) curves were estimated using the Kaplan-Meier method., Results: 23 patients were identified (mean age: 27; range 17-54). 91 decisions for DE were made (1 decision excluded because of progressive disease) with 90% concordance with guidelines. No adverse outcomes occurred as a result of the inappropriate escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23 patients) and 17.4% respectively with no difference for those who were DE. Males were less neutropenic after C1 and C3 of VDC compared to females (P-value C1 = 0.003; C3 = 0.005). VDC was associated with greater neutropenia on day 8 whereas IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non statistical difference in neutropenia was seen for individuals aged 15-25 (n = 13) compared with older individuals (P-value = 0.09). OS comparison for those with localized disease with a prior cohort who were not DE showed similar outcomes (P-value = 0.37)., Conclusions: DE is deliverable without increased adverse outcomes. Males have less myelosuppression during VDC, and should be especially considered for DE.

Background: Although Australian consensus guidelines support the use of ambulatory care strategies for management of adult patients with low-risk neutropenic fever (NF), few centres have successfully implemented viable programmes., Aims: To study the feasibility of an early discharge programme for adult patients with low-risk NF and assess organisational factors likely to influence successful implementation across participating Victorian hospitals., Methods: Four hospitals participated in an organisational readiness assessment preceding selection of a pilot site for programme implementation. Prospective baseline auditing of current practice (i.e. inpatient care until resolution of NF) across three hospitals preceded programme implementation and evaluation., Results: Barriers and facilitators to successful implementation were identified. One hundred and seventeen NF episodes were evaluated during audit phases. The frequency of low-risk NF presentations eligible for early discharge was low (less than two episodes per week). The programme reduced median (interquartile range) duration of parenteral antibiotics and length of stay for eligible patients (n = 11) from 4 (4, 5) days at baseline to 1 (1, 2) day during pilot (P = 0.02) and 4.5 (4, 5) days (baseline) to 2 (1, 3) days (pilot) (P = 0.02) respectively. The proportion of ineligible patients stepped down to oral antibiotics was improved from 38% (baseline) to 67% (pilot). No patients failed ambulatory care requiring readmission into hospital., Conclusion: The ambulatory care strategy for management of NF proposed by Australian consensus guidelines has been successfully piloted at a single Victorian centre. Organisational readiness tools can be used to identify potential barriers to the implementation of evidence based practices in patients with NF., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

Background: Thromboembolism is a common cause of morbidity and mortality in patients with colorectal cancer, but thromboprophylaxis (TP) is underutilized. Current guidelines do not make specific recommendations for colorectal cancer patients and provide minimal guidance for the ambulatory setting, although emerging evidence suggests TP may be warranted during chemoradiotherapy or in the extended post-operative phase. A survey of Australasian colorectal surgeons was therefore performed to assess current TP practice and attitudes., Methods: An online survey was sent to 204 surgeons who were members of the Colorectal Surgical Society of Australia and New Zealand., Results: One hundred twenty-eight surgeons (63%) completed the survey. Most surgeons consult available guidelines, and where recommendations are made, current practice is in line with them. Lack of data, lack of ownership, logistical issues and an absence of guideline recommendations currently prevent surgeons from instituting TP in the neoadjuvant treatment period. Fifty-four per cent of surgeons currently prescribe TP after hospital discharge; those that do not, cite logistical issues as the main constraint., Conclusion: More data on thromboembolism risk during various treatment phases are required and should be promulgated in tumour-specific guidelines. Logistical barriers to adopting TP in the ambulatory setting should be addressed., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Rituximab is the first and most widely adopted anti-CD20 monoclonal antibody, and has dramatically improved outcomes for patients with B-cell malignancies. Rituximab is active as a single agent and when combined with chemotherapy improves both response rates and survival compared with chemotherapy alone. This approach has become standard of care in this setting. A number of Phase III studies using extended applications of rituximab have demonstrated that patients achieve a significantly longer progression-free survival, at the cost of an increase in infective complications. This has resulted in the widespread adoption of maintenance rituximab following the completion of primary therapy. Rituximab is useful in both previously untreated patients and at relapse, although a subset of patients develop disease that is rituximab resistant, which along with histologic transformation remains a significant management problem for patients with follicular lymphoma. The toxicities are modest and manageable, including infusion reactions, late-onset neutropenia, impaired humoral immunity, reactivation of hepatitis and possibly pulmonary toxicity.

Objective: Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post-FCR in the era of highly sensitive molecular diagnostics and (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computerised tomography (CT)., Methods: All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database., Results: Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18) F-FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months)., Conclusion: Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post-FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: A multidisciplinary team from the Peter MacCallum Cancer Centre in Melbourne, Australia, developed a performance data suite to support a service improvement project based on lean manufacturing principles in its 19-chair chemotherapy day unit (CDU) and cytosuite chemotherapy production facility. The aims of the project were to reduce patient wait time and improve equity of access to the CDU., Methods: A project team consisting of a pharmacist and CDU nurse supported the management team for 10 months in engaging staff and customers to identify waste in processes, analyze root causes, eliminate non-value-adding steps, reduce variation, and level workloads to improve quality and flow. Process mapping, staff and patient tracking and opinion surveys, medical record audits, and interrogation of electronic treatment records were undertaken., Results: This project delivered a 38% reduction in median wait time on the day (from 32 to 20 minutes; P < .01), 7-day reduction in time to commencement of treatment for patients receiving combined chemoradiotherapy regimens (from 25 to 18 days; P < .01), and 22% reduction in wastage associated with expired drug and pharmacy rework (from 29% to 7%; P < .01). Improvements in efficiency enabled the cytosuite to increase the percentage of product manufactured within 10 minutes of appointment times by 29% (from 47% to 76%; P < .01)., Conclusion: A lean improvement methodology provided a robust framework for improved understanding and management of complex system constraints within a CDU, resulting in improved access to treatment and reduced waiting times on the day.

Aim: To assess thromboprophylaxis prescribing patterns against current guidelines and report thromboembolism (TE) incidence in multiple myeloma (MM) patients treated with thalidomide (thal) or lenalidomide (len) at a specialist cancer hospital over a one-year period., Method: Dispensing records of thal and len, diagnosis of MM, patients' characteristics, disease status, co-prescribed medicines including thromboprophylaxis and incidence of TE were extracted from patients' records and a patient survey conducted to identify patients who sourced thromboprophylactic medicines outside the hospital., Results: Enoxaparin was most the commonly prescribed thromboprophylactic agent (43%), followed by low-dose aspirin (26%) and therapeutic warfarin (6%). The thromboprophylactic strategy (including no prophylaxis) could not be determined for 22% of patients. TE incidence (with any thromboprophylaxis) was 9.3 and 9.1% in thal-based and len-based regimens, respectively., Conclusion: Both aspirin and enoxaparin thromboprophylaxis were prescribed for patients on both low-risk and high-risk immunomodulatory drug-based regimens, deviating from current consensus guidelines. Treatment of comorbidities constituted the rationale for maintenance on therapeutic warfarin. Fixed low-dose warfarin was not prescribed. TE event rates (with any thromboprophylaxis) were consistent with those reported in the literature. Documentation of a chosen strategy was lacking for nearly a quarter of patients, resulting in uncertainty of treatment plan for other members of the multidisciplinary treating team. Centers need to work towards evidence-based institutional guidelines and improving documentation practices for thromboprophylaxis in their MM patients., (© 2012 Wiley Publishing Asia Pty Ltd.)

Unlabelled: Preventable medication errors impact substantially on the Australian healthcare system. Where 'poor communication of medical information at transition points is responsible for as many as 50% of all medication errors', a leading contributor for this type of medication error is lack of consumer knowledge about medicines information. This study was aimed at designing and testing the effectiveness of a consumer-healthcare professional partnership model towards effective medication reconciliation. This model aims to empower consumers about their medicines information, so that they would contribute more effectively to medication reconciliation and thereby minimise medication errors occurring at transition points. Components of this model were informed by qualitative data gleaned from patient opinion surveys, focus group sessions involving nurses, doctors and pharmacists working at the hospital and results of a literature search of medication safety tools. Programme development was informed by health improvement approaches centred on a Plan-Do-Study-Act cycle. Evaluation for effectiveness was conducted within a framework of a controlled before and after study., Results: revealed that there was a 1.4-fold increase in the reporting rate of pharmacists intervention. The study could not demonstrate that the designed intervention was effective in minimising near-misses. However, there is statistically insignificant reduction in errors for patients that were correctly exposed to the intervention. Anecdotal evidence suggests there is utility for a patient population keen to claim greater ownership of their medicines information. Further, we advocate that patient education about medicines and the establishment of a consumer-healthcare professional model occur prior to ward admission.

Background: Adult febrile neutropenic oncology patients, at low risk of developing medical complications, may be effectively and safely managed in an ambulatory setting, provided they are appropriately selected and adequate supportive facilities and clinical services are available to monitor these patients and respond to any clinical deterioration., Methods: A cost analysis was modelled using decision tree analysis, published cost and effectiveness parameters for ambulatory care strategies and data from the State of Victoria's hospital morbidity dataset. Two-way sensitivity analyses and Monte Carlo simulation were performed to evaluate the uncertainty of costs and outcomes associated with ambulatory care., Results: The modelled cost analysis showed that cost savings for two ambulatory care strategies were ~30% compared to standard hospital care. The weighted average cost saving per episode of 'low-risk' febrile neutropenia using Strategy 1 (outpatient follow-up only) was 35% (range: 7-55%) and that for Strategy 2 (early discharge and outpatient follow-up) was 30% (range: 7-39%). Strategy 2 was more cost-effective than Strategy 1 and was deemed the more clinically favoured approach., Conclusion: This study outlines a cost structure for a safe and comprehensive ambulatory care program comprised of an early discharge pathway with outpatient follow-up, and promotes this as a cost effective approach to managing 'low-risk' febrile neutropenic patients.

Administration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta-lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk. Due consideration is given to the appropriate use of glycopeptides in this setting. Several clinical caveats, accounting for institution- and patient-specific risk factors, are provided to help guide the judicious use of the agents described. Detailed recommendations are also provided regarding time to first dose, timing of blood cultures, selection of a first-line antibiotic regimen, subsequent modification of antibiotic choice and cessation of therapy., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Utilization of risk-stratification tools in the setting of neutropenic fever is currently limited by inadequate knowledge and lack of awareness. Within this context, the approach to management of low-risk patients with neutropenic fever is inconsistent with the available evidence across many Australian treating centres. These clinical guidelines define and clarify an accepted standard of care for this patient group given the current evidence base. The Multinational Association for Supportive Care in Cancer risk index is presented as the preferred risk assessment tool for determining patient risk. Suitability of ambulatory care within specific patient populations is discussed, with defined eligibility criteria provided to guide clinical decision-making. Detailed recommendations for implementing appropriate ambulatory strategies, such as early discharge and outpatient antibiotic therapy, are also provided. Due consideration is given to infrastructural requirements and other supportive measures at a resourcing and operational level. An analysis of the relevant health economics is also presented., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: Although the incidence of neutropenic fever (FN) is estimated to be up to 80% for some malignancies, the epidemiological characteristics and economic burden are not well understood for Australian patients., Aims: To describe underlying malignant conditions, potential aetiologies, clinical outcomes and healthcare utilization for an Australian population with FN, and to estimate the economic burden of this condition within the Australian healthcare sector., Methods: Epidemiological features of FN were extracted from a population-based hospital morbidity dataset, the Victorian Admitted Episodes Dataset (VAED), for a 12-month period (2008). These were analysed according for a range of malignancy categories. Economic burden of hospitalizations was estimated according to data presented in the Round 12 National Hospital Cost Data Collection Report., Results: A total of 2599 admitted episodes across 92 Victorian hospitals fulfilled inclusion criteria for FN. Metropolitan hospitalizations accounted for 79% episodes. FN illness comprised underlying solid tumours diagnoses (40%), followed by leukaemia (29.3%), lymphoma (22%) and myeloma (8.5%). Length of hospital stay was >15 days for approximately one-third of hospitalizations. intensive care unit admission rates were 5.9-11.7%. Weighted average costs of hospitalization (AUD) for solid tumours, lymphoma, myeloma and leukaemia were $8309 ± $391, 18,145 ± $1602, $21,764 ± $1289 and $22,596 ± $2618 respectively., Conclusions: Using VAED indices, epidemiological features of Australian patients with FN appear comparable with international reports. In contrast to US data, estimated healthcare costs are up to 50% lower in the Australian healthcare sector. These data offer important insights for prioritizing of research agendas and resource allocation., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

The use of oral prophylactic antibiotics in patients with neutropenia is controversial and not recommended by this group because of a lack of evidence showing a reduction in mortality and concerns that such practice promotes antimicrobial resistance. Recent evidence has demonstrated non-significant but consistent, improvement in all-cause mortality when fluoroquinolones (FQs) are used as primary prophylaxis. However, the consensus was that this evidence was not strong enough to recommend prophylaxis. The evidence base for FQ prophylaxis is presented alongside current consensus opinion to guide the appropriate and judicious use of these agents. Due consideration is given to patient risk, as it pertains to specific patient populations, as well as the net effect on selective pressure from antibiotics if FQ prophylaxis is routinely used in a target population. The potential costs and consequences of emerging FQ resistance, particularly among Escherichia coli, Clostridium difficile and Gram-positive organisms, are considered. As FQ prophylaxis has been advocated in some chemotherapy protocols, specific regard is given to whether FQ prophylaxis should be used to support these regimens. The group also provides recommendations for monitoring and surveillance of emerging resistance in those centres that have adopted FQ prophylaxis., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

The current consensus guidelines were developed to standardize the clinical approach to the management of neutropenic fever in adult cancer patients throughout Australian treating centres. The three areas of clinical practice covered by the guidelines, the process for developing consensus opinion, and the system used to grade the evidence and relative strength of recommendations are described. The health economics implications of establishing clinical guidance are also discussed., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: An abundance of new evidence regarding treatment strategies for neutropenic fever is likely to contribute to variability in practice across institutions and clinicians alike., Aims: To describe current clinical practices in Australia, by surveying haematologists, oncologists and infectious diseases physicians involved in cancer care., Methods: Clinician members from Australian professional associations, accounting for the vast majority of Australian cancer specialists, were invited to participate in an electronic survey, comprising of a clinical case-based questionnaire. Clinical practice areas explored were: use of risk-assessment and empiric antibiotic strategies across various treatment settings; use of anti-bacterial prophylaxis; and use of granulocyte-colony stimulating factors for established neutropenic fever and for secondary prophylaxis., Results: A total of 252 clinicians returned responses (approximately 30% response rate). The majority (>70%) were representative of practices in public, major city, tertiary referral hospitals. Less than half of clinicians were aware of risk-assessment tools and less than quarter currently used ambulatory care strategies. If adequate resources were made available, more than 80% were willing to use risk-assessment tools and 60% more clinicians were likely to use ambulatory care strategies. Most clinicians prescribed dual therapy parenteral antibiotics, even for clinically stable patients (53% haematologists, 56% oncologists). Granulocyte-colony stimulating factor was used frequently as secondary prophylaxis in the breast cancer case (91%), follicular lymphoma case (59%) and non-small cell lung cancer case (31%). Fluoroquinolone prophylaxis was infrequently prescribed (19% oncologists, 30% haematologists)., Conclusions: Evidence-practice gaps were identified around the use of risk-assessment-based empiric therapy, and help to inform better clinical guidance., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)