Keefe D.,Royal Adelaide Hospital |
Keefe D.,Royal Adelaide Hospital Cancer Center |
Bowen J.,Royal Adelaide Hospital |
Gibson R.,University of Adelaide |
And 4 more authors.
Oncologist | Year: 2011
Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities. Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/ Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. © AlphaMed Press.
Brown M.P.,Royal Adelaide Hospital Cancer Center |
Brown M.P.,University of Adelaide |
Staudacher A.H.,University of Adelaide |
Staudacher A.H.,Center for Cancer Biology
Immunotherapy | Year: 2014
Evaluation of: Younes A, Connors JM, Park SI et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a Phase 1, open-label, dose-escalation study. Lancet Oncol. 14(13), 1348-1356 (2013). With exceptionally high response rates, the CD30-directed antibody-drug conjugate brentuximab vedotin (BV) was US FDA approved for treatment of patients with relapsed/refractory Hodgkin lymphoma (HL). Now in Phase I clinical trial, it has been shown that combining BV with multiagent chemotherapy (excluding bleomycin) as first-line treatment in HL patients with high-risk disease is feasible. Complete response rates were over 90% and toxicity was manageable. Given that the malignant cell population comprises a minority of HL lesions, and that BV releases a diffusible cytotoxin via a cathepsin B-cleavable linker, we argue that a significant proportion of the antitumor activity of BV can be attributed to bystander cytotoxicity in addition to direct killing of CD30-expressing malignant cells. © 2014 Future Medicine Ltd.
Lees J.,Royal Adelaide Hospital Cancer Center |
Chan A.,National University of Singapore
The Lancet Oncology | Year: 2011
More and more elderly people with cancer are treated in oncology clinics worldwide every year, many of whom have comorbid disorders treated with one or more drugs. Moreover, these patients might also take self-prescribed over-the-counter drugs or complementary and alternative medicines, which they might not tell their doctor about. Initiation of chemotherapy with one or more cytotoxic or targeted agents and drugs for treatment of cancer symptoms or toxic effects related to treatment can result in polypharmacy. We examine the clinical implications of polypharmacy. Challenges for the medical teams who treat elderly patients with cancer include identification of what drugs are actually being taken by the patient, avoidance or management of any adverse effects or drug interactions, and reassessing the patient's overall treatment. We address these issues and propose practical recommendations for management of treatment for elderly patients with cancer. © 2011 Elsevier Ltd.
Al-Azri A.R.,University of Adelaide |
Al-Azri A.R.,Ministry of Health |
Gibson R.J.,University of Adelaide |
Keefe D.M.K.,Royal Adelaide Hospital Cancer Center |
Logan R.M.,University of Adelaide
Oral Diseases | Year: 2013
Matrix metalloproteinases (MMPs) are critical factors in maintaining the integrity of mucosa and mediating normal biological processes. An imbalance between tissue levels of these mediators and their natural inhibitors is believed to underlie the pathophysiology of many diseases, including those affect the gastrointestinal and oral mucosae. The ongoing development of synthetic inhibitors of these mediators may provide opportunities to develop treatment modalities for patients suffering from these diseases. Understanding the role of MMPs in the pathophysiology of many diseases, however, is far from complete, and the improvement of pharmaceutical management strategies can only be achieved if the underlying process of these diseases is completely comprehended. This paper reviews the functions of matrix metalloproteinases and addresses their role in mediating mucosal pathologies with emphasis on oral mucosa. © 2012 John Wiley & Sons A/S.
Al-Ejeh F.,Queensland Institute of Medical Research |
Kumar R.,University of Adelaide |
Wiegmans A.,Queensland Institute of Medical Research |
Lakhani S.R.,University of Queensland |
And 3 more authors.
Oncogene | Year: 2010
The DNA-damage response (DDR) pathways consist of interconnected components that respond to DNA damage to allow repair and promote cell survival. The DNA repair pathways and downstream cellular responses have diverged in cancer cells compared with normal cells because of genetic alterations that underlie drug resistance, disabled repair and resistance to apoptosis. Consequently, abrogating DDR pathways represents an important mechanism for enhancing the therapeutic index of DNA-damaging anticancer agents. In this review, we discuss the DDR pathways that determine antitumor effects of DNA-damaging agents with a specific focus on treatment outcomes in tumors carrying a defective p53 pathway. Finely tuned survival and death pathways govern the cellular responses downstream of the cytotoxic insults inherent in anticancer treatment. The significance and relative contributions of cellular responses including apoptosis, mitotic catastrophe and senescence are discussed in relation to the web of molecular interactions that affect such outcomes. We propose that promising combinations of DNA-damaging anticancer treatments with DDR-pathway inhibition would be further enhanced by activating downstream apoptotic pathways. The proposed rationale ensures that actual cell death is the preferred outcome of cancer treatment instead of other responses, including reversible cell cycle arrest, autophagy or senescence. Finally, to better measure the contribution of different cellular responses to anticancer treatments, multiplex in vivo assessments of therapy-induced response pathways such as cell death, senescence and mitotic catastrophe is desirable rather than the current reliance on the measurement of a single response pathway such as apoptosis. © 2010 Macmillan Publishers Limited All rights reserved.
Ramm D.,Royal Adelaide Hospital Cancer Center |
Ramm D.,University of Adelaide |
Rutten T.P.,Royal Adelaide Hospital Cancer Center |
Shepherd J.,Royal Adelaide Hospital Cancer Center |
And 2 more authors.
Physics in Medicine and Biology | Year: 2012
Optical CT scanners for a 3D readout of externally irradiated radiosensitive hydrogels currently require the use of a refractive index (RI) matching liquid bath to obtain suitable optical ray paths through the gel sample to the detector. The requirement for a RI matching liquid bath has been negated by the design of a plastic cylindrical gel container that provides parallel beam geometry through the gel sample for the majority of the projection. The design method can be used for various hydrogels. Preliminary test results for the prototype laser beam scanner with ferrous xylenol-orange gel show geometric distortion of 0.2mm maximum, spatial resolution limited to beam spot size of about 0.4mm and 0.8% noise (1 SD) for a uniform irradiation. Reconstruction of a star pattern irradiated through the cylinder walls demonstrates the suitability for external beam applications. The extremely simple and cost-effective construction of this optical CT scanner, together with the simplicity of scanning gel samples without RI matching fluid increases the feasibility of using 3D gel dosimetry for clinical external beam dose verifications. © 2012 Institute of Physics and Engineering in Medicine.
Ramm D.,Royal Adelaide Hospital Cancer Center |
Ramm D.,University of Adelaide
Journal of Physics: Conference Series | Year: 2013
Ongoing progress on development of an in-air scanning optical CT is reported, specifically dealing with the minimization of scanner imaging artefacts. Improved scratch resistance of the PMMA gel cylinder was a primary goal, so that routine cleaning would not degrade the polished surfaces. This was achieved by the addition of a hard coating to the cylinder surfaces. New artefacts were introduced and subsequently reduced by alternative processing of projection data. The outcome was a gel cylinder of much greater practicality for routine use while maintaining similar signal to noise ratios and uniformity in the image reconstruction field of view.
Prouse J.,Royal Adelaide Hospital Cancer Center
Clinical Journal of Oncology Nursing | Year: 2010
A systematic review of the literature regarding the effectiveness of various methods of information given to patients with cancer receiving chemotherapy education revealed that psycho-educational interventions minimized the intensity and impact of treatment-related fatigue on daily life in the short term for patients undergoing chemotherapy. Studies that investigated efficacy of interactive multimedia devices revealed no statistical improvement in information recall, quantity of self-care activities, and fatigue levels between groups. Three of the multimedia studies focused on anxiety and depression trends before and during treatment, with mixed results. Several studies revealed no significant difference in either anxiety or depression. Others concluded that patients who viewed video information in conjunction with standard care were less anxious and depressed. Combined, these studies revealed that multimedia devices did not improve recall of information and that psycho-educational interventions were able to improve the impact of treatment-related side effects, namely fatigue, in the short term. This suggests that the educational needs of patients with cancer require a complex series of factors that impact the individual's ability to understand how and when to initiate recommended self-care strategies.
Brown M.P.,Royal Adelaide Hospital Cancer Center
Immunotherapy | Year: 2011
For the first time, a pivotal Phase III clinical trial has demonstrated an overall survival benefit for an antimelanoma drug, ipilimumab, in previously treated advanced melanoma patients. Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4. All patients in this study were HLA-A2*0201 positive because the active control arm contained a HLA-A2*0201-restricted peptide derived from the melanocyte differentiation antigen, gp100. Hence, the following question arises: does the survival benefit conferred by ipilimumab treatment only benefit HLA-A2*0201-positive melanoma patients? However, the current paper reveals a retrospective analysis to show that advanced melanoma patients obtain a survival benefit from ipilimumab irrespective of HLA-A2*0201 status. This analysis also raises other interesting questions regarding the HLA dependence of mechanisms underlying the toxicity and antimelanoma activity of ipilimumab, which are discussed. © 2011 Future Medicine Ltd.
Olver I.N.,Royal Adelaide Hospital Cancer Center |
Dutney A.,Flinders University
Alternative Therapies in Health and Medicine | Year: 2012
Context Cochrane reviews have analyzed multiple studies on intercessory prayer that treatment teams had added to health interventions; however, the reviewers could draw no conclusions about the efficacy of prayer because the studies showed either positive or no effects and used different endpoints and methodologies. Objective The study intended to determine whether researchers could measure the impact of intercessory prayer on spiritual well-being. Design The research team conducted a randomized blinded trial of intercessory prayer added to normal cancer treatment with participants agreeing to complete quality of life (QOL) and spiritual well-being scales at baseline and 6 months later. The research team had shown previously that spiritual well-being is an important, unique domain in the assessment of QOL. Participants remained blinded to the randomization. Based on a previous study, the research team determined that the study required a sample of 1000 participants to detect small differences (P =.05, 2-tailed, 80% power). Setting The research team performed this research at the Royal Adelaide Hospital Cancer Centre, South Australia, Australia. Participants: Participants were patients at the cancer center between June 2003 and May 2008. Of 999 participants with mixed diagnoses who completed the baseline questionnaires, 66.6% provided follow-up. The average age was 61 years, and most participants were married/de facto (living with partners), were Australians or New Zealanders living in Australia, and were Christian. Intervention The research team asked an external group offering Christian intercessory prayer to add the study's participants to their usual prayer lists. They received details about the participants, but this information was not sufficient to identify them. Outcome Measures The research team used the Functional Assessment of Chronic Illness Therapy- Spiritual Well-being questionnaire to assess spiritual wellbeing and QOL. Results The intervention group showed significantly greater improvements over time for the primary endpoint of spiritual well-being as compared to the control group (P =.03, partial η 2 =.01). The study found a similar result for emotional well-being (P =.04, partial η 2 =.01) and functional well-being (P =.06, partial η 2 =.01). Conclusions Participants with cancer whom the research team randomly allocated to the experimental group to receive remote intercessory prayer showed small but significant improvements in spiritual well-being.