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Kurralta Park, Australia

Parente P.,Medical Oncology | Parente P.,Monash University | Parnis F.,Adelaide Cancer Center | Gurney H.,Clinical Research
Asia-Pacific Journal of Clinical Oncology | Year: 2014

Prior to 2010, docetaxel was the standard option for chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Today, the picture is vastly different: several additional therapies have each demonstrated a survival benefit such that we now have chemotherapy (cabazitaxel), androgen suppressive agents (abiraterone acetate and enzalutamide), a cellular vaccine (sipuleucel-T) and radium-233 (for symptomatic bone metastases). With several other agents in the pipeline for late-stage disease, the future looks promising for mCRPC. As the available data are not able to inform as to the optimum sequencing of therapy, this remains a challenge. This paper draws on insights from published and ongoing clinical studies to provide a practical patient-focused approach to maximize the benefits of the current therapeutic armamentarium. Preliminary sequencing suggestions are made based on clinical trial criteria. But until more data become available, clinical gestalt, experience, cost and individual patient preferences will continue to drive choices. © 2014 Wiley Publishing Asia Pty Ltd. Source

Wickham N.,Adelaide Cancer Center | Gallus A.S.,Flinders University | Walters B.N.J.,The University of Notre Dame Australia | Wilson A.,Research Translation Group Melbourne
Internal Medicine Journal | Year: 2012

Each year in Australia, about 1 in 1000 people develop a first episode of venous thromboembolism (VTE), which approximates to about 20000 cases. More than half of these episodes occur during or soon after a hospital admission, which makes them potentially preventable. This paper summarises recommendations from the National Health and Medical Research Council's 'Clinical Practice Guideline for the Prevention of Venous Thromboembolism in Patients Admitted to Australian Hospitals' and describes the way these recommendations were developed. The guideline has two aims: to provide advice on VTE prevention to Australian clinicians and to support implementation of effective programmes for VTE prevention in Australian hospitals by offering evidence-based recommendations which local hospital guidelines can be based on. Methods for preventing VTE are pharmacological and/or mechanical, and they require appropriate timing, dosing and duration and also need to be accompanied by good clinical care, such as promoting mobility and hydration whilst in hospital. With some procedures or injuries, the risk of VTE is sufficiently high to require that all patients receive an effective form of prophylaxis unless this is contraindicated; in other clinical settings, the need for prophylaxis requires individual assessment. For optimal VTE prevention, all patients admitted to hospital should have early and formal assessments of: (i) their intrinsic VTE risk and the risks related to their medical conditions; (ii) the added VTE risks resulting from surgery or trauma; (iii) bleeding risks that would contraindicate pharmacological prophylaxis; (iv) any contraindications to mechanical prophylaxis, culminating in (v) a decision about prophylaxis (pharmacological and/or mechanical, or none). The most appropriate form of prophylaxis will depend on the type of surgery, medical condition and patient characteristics. Recommendations for various clinical circumstances are provided as summary tables with relevance to orthopaedic surgical procedures, other types of surgery and medical inpatients. In addition, the tables indicate the grades of supporting evidence for the recommendations (these range from Grade A which can be trusted to guide practice, to Grade D where there is more uncertainty; Good Practice Points are consensus-based expert opinions). © 2012 National Health and Medical Research Council. Internal Medicine Journal © 2012 Royal Australasian College of Physicians. Source

Chan A.,Curtin University Australia | Shannon C.,Adult Materials Hospital | de Boer R.,Epworth Freemasons Hospital | Baron-Hay S.,Royal Northshore Hospital | And 6 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2014

Aim: To evaluate the efficacy and tolerability of lapatinib (L) and intravenous vinorelbine (V) in patients with metastatic HER2-positive breast cancer who have previously received two lines of anti-HER2 therapy (i.e. trastuzumab [T] with chemotherapy and lapatinib with capecitabine [LC]). Method: Consenting patients with measurable or evaluable disease and normal cardiac function who had progressed were recruited. Patients received LV (lapatinib 1250mg orally daily, vinorelbine 20mg/m2 intravenously on days 1 and 8 every 3 weeks) until progressive disease, intolerable toxicity or patient request. Results: The trial was closed early following inclusion of 19 patients due to slow accrual. Ten, five and four patients had received two, three andmore thanfour lines of chemotherapy with T and LC, respectively, prior to study entry. Patients received a median of 5 cycles (range 1-18) of LV. Confirmed partial response was seen in 2 of 16 patients with measurable disease (12.5%); stable disease>24 weeks was seen in two patients (10.5%) with a clinical benefit rate of 20%. Fatigue and any grade neutropenia occurred commonly, but grade 4 severity occurred in only 5 and 11%, respectively. There were no episodes of cardiac dysfunction and no treatment-related deaths. The median progression-free survival was 3.9 months and overall survival (OS) was 9.1 months. Conclusion: The combination of LV demonstrated modest efficacy but was well tolerated. This combination may be of benefit to those patients who are unable to access the newer anti-HER2 agents and the low rate of treatment-emergent adverse effects will enable patients' symptoms, such as pain, to be minimized. © 2014 Wiley Publishing Asia Pty Ltd. Source

Kotasek D.,Adelaide Cancer Center | Tebbutt N.,Medical Oncology Unit | Desai J.,Royal Melbourne Hospital | Welch S.,University of Toronto | And 6 more authors.
BMC Cancer | Year: 2011

Background: This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors.Methods: Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6).Results: Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2), 2 (n = 4), 3 (n = 3), and 6 (n = 2). The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19), nausea (n = 18), vomiting (n = 13), and fatigue (n = 12), which were mostly of worst grade < 3. The pharmacokinetics of motesanib was not markedly affected by coadministration of gemcitabine and erlotinib, or erlotinib alone. Erlotinib exposure, however, appeared lower after coadministration with gemcitabine and/or motesanib. Of 49 evaluable patients, 1 had a confirmed partial response and 26 had stable disease.Conclusions: Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone.Trial Registration: ClinicalTrials.gov NCT01235416. © 2011 Kotasek et al; licensee BioMed Central Ltd. Source

Vermorken J.B.,University of Antwerp | Stohlmacher-Williams J.,Universitatsklinikum Carl Gustav Carus | Davidenko I.,Krasnodar City Oncology Center | Licitra L.,Fondazione Istituto Nazionale Tumori | And 14 more authors.
The Lancet Oncology | Year: 2013

Background: Previous trials have shown that anti-EGFR monoclonal antibodies can improve clinical outcomes of patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SCCHN). We assessed the efficacy and safety of panitumumab combined with cisplatin and fluorouracil as first-line treatment for these patients. Methods: This open-label phase 3 randomised trial was done at 126 sites in 26 countries. Eligible patients were aged at least 18 years; had histologically or cytologically confirmed SCCHN; had distant metastatic or locoregionally recurrent disease, or both, that was deemed to be incurable by surgery or radiotherapy; had an Eastern Cooperative Oncology Group performance status of 1 or less; and had adequate haematological, renal, hepatic, and cardiac function. Patients were randomly assigned according to a computer-generated randomisation sequence (1:1; stratified by previous treatment, primary tumour site, and performance status) to one of two groups. Patients in both groups received up to six 3-week cycles of intravenous cisplatin (100 mg/m2 on day 1 of each cycle) and fluorouracil (1000 mg/m2 on days 1-4 of each cycle); those in the experimental group also received intravenous panitumumab (9 mg/kg on day 1 of each cycle). Patients in the experimental group could choose to continue maintenance panitumumab every 3 weeks. The primary endpoint was overall survival and was analysed by intention to treat. In a prospectively defined retrospective analysis, we assessed tumour human papillomavirus (HPV) status as a potential predictive biomarker of outcomes with a validated p16-INK4A (henceforth, p16) immunohistochemical assay. Patients and investigators were aware of group assignment; study statisticians were masked until primary analysis; and the central laboratory assessing p16 status was masked to identification of patients and treatment. This trial is registered with ClinicalTrials.gov, number NCT00460265. Findings: Between May 15, 2007, and March 10, 2009, we randomly assigned 657 patients: 327 to the panitumumab group and 330 to the control group. Median overall survival was 11·1 months (95% CI 9·8-12·2) in the panitumumab group and 9·0 months (8·1-11·2) in the control group (hazard ratio [HR] 0·873, 95% CI 0·729-1·046; p=0·1403). Median progression-free survival was 5·8 months (95% CI 5·6-6·6) in the panitumumab group and 4·6 months (4·1-5·4) in the control group (HR 0·780, 95% CI 0·659-0·922; p=0·0036). Several grade 3 or 4 adverse events were more frequent in the panitumumab group than in the control group: skin or eye toxicity (62 [19%] of 325 included in safety analyses vs six [2%] of 325), diarrhoea (15 [5%] vs four [1%]), hypomagnesaemia (40 [12%] vs 12 [4%]), hypokalaemia (33 [10%] vs 23 [7%]), and dehydration (16 [5%] vs seven [2%]). Treatment-related deaths occurred in 14 patients (4%) in the panitumumab group and eight (2%) in the control group. Five (2%) of the fatal adverse events in the panitumumab group were attributed to the experimental agent. We had appropriate samples to assess p16 status for 443 (67%) patients, of whom 99 (22%) were p16 positive. Median overall survival in patients with p16-negative tumours was longer in the panitumumab group than in the control group (11·7 months [95% CI 9·7-13·7] vs 8·6 months [6·9-11·1]; HR 0·73 [95% CI 0·58-0·93]; p=0·0115), but this difference was not shown for p16-positive patients (11·0 months [7·3-12·9] vs 12·6 months [7·7-17·4]; 1·00 [0·62-1·61]; p=0·998). In the control group, p16-positive patients had numerically, but not statistically, longer overall survival than did p16-negative patients (HR 0·70 [95% CI 0·47-1·04]). Interpretation: Although the addition of panitumumab to chemotherapy did not improve overall survival in an unselected population of patients with recurrent or metastatic SCCHN, it improved progression-free survival and had an acceptable toxicity profile. p16 status could be a prognostic and predictive marker in patients treated with panitumumab and chemotherapy. Prospective assessment will be necessary to validate our biomarker findings. Funding: Amgen Inc. © 2013 Elsevier Ltd. Source

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