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Newcastle, Australia

Davey R.J.,Hunter Medical Research Institute | Westhuizen A.V.D.,Calvary Materials Hospital | Bowden N.A.,Hunter Medical Research Institute
Critical Reviews in Oncology/Hematology | Year: 2016

Metastatic melanoma is an aggressive form of cancer characterised by poor prognosis and a complex etiology. Until 2010, the treatment options for metastatic melanoma were very limited. Largely ineffective dacarbazine, temozolamide or fotemustine were the only agents in use for 35 years. In recent years, the development of molecularly targeted inhibitors in parallel with the development of checkpoint inhibition immunotherapies has rapidly improved the outcomes for metastatic melanoma patients. Despite these new therapies showing initial promise; resistance and poor duration of response have limited their effectiveness as monotherapies. Here we provide an overview of the history of melanoma treatment, as well as the current treatments in development. We also discuss the future of melanoma treatment as we go beyond monotherapies to a combinatorial approach. Combining older therapies with the new molecular and immunotherapies will be the most promising way forward for treatment of metastatic melanoma. © 2015 Elsevier Ireland Ltd. Source

Price T.J.,The Queen Elizabeth Hospital | Price T.J.,University of Adelaide | Zannino D.,University of Sydney | Wilson K.,University of Sydney | And 8 more authors.
Annals of Oncology | Year: 2012

Background: In an ageing population, a greater proportion of geriatric patients will be considered for systemic chemotherapy. Colorectal cancer (CRC) is a common malignancy and will be a major health issue in geriatrics. We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy. Patients and methods: MAX, a three arm study of Capecitabine (C) versus CBevacizumab (CB) versus CBMitomycin C (CBM), found an improvement in progression-free survival (PFS), with addition of B [+/- mitomycin C (MMC)] to C. This analysis assesses the effect of adding B (+/- MMC) to C on PFS, overall survival (OS), response rate (RR), toxicity and dose intensity in geriatric patients (age ≥ 75 years). Results: Ninety-nine patients (21%) were aged 75-86 years. Baseline characteristics were well balanced. Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m. 2/day; days 1-14, q21 (61% for <75 years) and 88% were Eastern Cooperative Oncology Group 0-1. Co-morbidities were as expected in this population. The addition of B significantly improved PFS in geriatric patients(C 5.8 months versus CB 8.8 months, Hazard ratio (HR) 0.65 and C versus CBM 10.4 months HR 0.38). The interaction test for OS, RR and PFS revealed no impact of age. Dose intensity was maintained >90% in all patients. There were no major differences in toxicity patterns between age cohorts. Conclusions: Addition of B to C significantly improved PFS in this geriatric population, with similar benefits to those aged <75 years. Treatment was well tolerated with no signal of increased toxicity (including thromboembolism) when compared with those aged <75 years. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Brown S.G.A.,Western Research Institute | Brown S.G.A.,University of Western Australia | Stone S.F.,Western Research Institute | Stone S.F.,University of Western Australia | And 11 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background Prospective human studies of anaphylaxis and its mechanisms have been limited, with few severe cases or examining only 1 or 2 mediators. Objectives We wanted to define the clinical patterns of anaphylaxis and relationships between mediators and severity. Methods Data were collected during treatment and before discharge. Serial blood samples were taken for assays of mast cell tryptase, histamine, anaphylatoxins (C3a, C4a, C5a), cytokines (IL-2, IL-6, IL-10), soluble tumor necrosis factor receptor I, and platelet activating factor acetyl hydrolase. Principal component analysis defined mediator patterns, and logistic regression identified risk factors and mediator patterns associated with reaction severity and delayed reactions. Results Of 412 reactions in 402 people, 315 met the definition for anaphylaxis by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network. Of 97 severe reactions 45 (46%) were hypotensive, 23 (24%) were hypoxemic, and 29 (30%) were mixed. One patient died. Severe reactions were associated with older age, pre-existing lung disease, and drug causation. Delayed deteriorations treated with epinephrine occurred in 29 of 315 anaphylaxis cases (9.2%) and were more common after hypotensive reactions and with pre-existing lung disease. Twenty-two of the 29 delayed deteriorations (76%) occurred within 4 hours of initial epinephrine treatment. Of the remaining 7 cases, 2 were severe and occurred after initially severe reactions, within 10 hours. All mediators were associated with severity, and 1 group (mast cell tryptase, histamine, IL-6, IL-10, and tumor necrosis factor receptor I) was also associated with delayed deteriorations. Low platelet activating factor acetyl hydrolase activity was associated with severe reactions. Conclusion The results suggest that multiple inflammatory pathways drive reaction severity and support recommendations for safe observation periods after initial treatment. © 2013 American Academy of Allergy, Asthma & Immunology. Source

Foy A.,Maitland Clinical School | Tierney A.,Calvary Materials Hospital
Internal Medicine Journal | Year: 2014

Background: Provision of internal medicine services in rural Australia is always problematic. Aim: The aim was to undertake an audit of an outreach service operating in Northern New South Wales since 2006. Methods: The service is conducted eight times a year, involving a consultant and an advanced trainee who travel by car to the towns of Moree and Mungindi and conduct clinics in a general practice setting, an Aboriginal medical service and a local health district clinic. Since 2008, a cardiology service and a diabetes service have been added on a fly-in fly-out basis. Case records of all patients enrolled in the service between February 2006 and July 2013 were reviewed in determining the demographics, clinical presentations and level of service coverage. The experience of the authors in establishing the service provided insights into the challenges and the success factors involved. Results: Five hundred and eighty-three patients were seen on a total of 1070 occasions relating to a wide variety of clinical presentations. Of these, 31.3% were indigenous compared with 20% in the local statistical area, and both indigenous and non-indigenous patients were seen in all settings. Patients fell into 15 different diagnostic categories with indigenous patients more likely to present for diabetes (P < 0.001) and hepatitis B (P < 0.01), but less likely to present for treatment of hepatitis C (P < 0.01). Conclusions: In providing an outreach service to a mixed community, flexibility in both setting and personnel are essential. Diabetes and liver disease are highly prevalent in indigenous patients, but the low numbers presenting for hepatitis C requires further study. © 2014 Royal Australasian College of Physicians. Source

Douglas C.D.,University of Newcastle | Low N.C.K.,Calvary Materials Hospital | Seitz M.J.,John Hunter Hospital
Annals of Surgical Oncology | Year: 2013

Background: The keystone flap is being promoted as an advance in oncological surgical reconstruction. Wound closure with this island flap involves two V-Y advancements toward the center and along the long axis of the island, at right angles to the line of maximum tension when the wound is closed. It is implied that the long-axis advancements enable closure by relaxing the entire flap of skin, allowing it to be stretched more easily along the short axis. We undertook a study to test this hypothesis. Methods: We measured tension and extension along perpendicular axes in nine freshly excised specimens of human skin. We held the longitudinal axis fixed while stretching the skin along the transverse axis. We then released the longitudinal axis and measured the resultant drop in transverse tension. Finally, we increased the transverse tension to approximately its previous level, and measured the new transverse extension. Results: There was significant interdependence between longitudinal and transverse tensions. The fall in transverse wound tension associated with longitudinal release varied with starting tensions and with the original site and orientation of the specimen. In the five cases where the longitudinal release was from the in vivo length, the mean increase in transverse stretch attributable to the release was 0.6 mm (95 % confidence interval 0.1-1.1 mm). Discussion: The increase in transverse stretch that can be achieved by releasing skin from its longitudinal in vivo length appears trivial, raising questions about the rationale for the use of the prototypical (type 1) keystone flap in wound closure. © 2012 Society of Surgical Oncology. Source

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