Value Of Androgen Deprivation And Bisphosphonate In Patients Treated By Radiotherapy For Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,533,827.00
Summary
Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has ex ....Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has exceeded expectations and 728 patients have already been recruited, it is anticipated that the recruitment target will be reached in mid 2007. Patients are randomly assigned to receive one of four treatment options in the RADAR trial. The first option: Option A: Radiation Therapy and 6 months of Hormone Therapy (Leuprorelin acetate), is currently the standard of care. Option C is a further 12 months of hormone therapy after the current standard of care. Two of the options (B and D) are identical to options A and C except that subjects also receive 18 months of zoledronate (a 'bone' drug) in addition to hormone therapy and radiotherapy. The main goal of the RADAR trial is to determine whether 12 months of hormone therapy using Leuprorelin acetate starting immediately after standard therapy (ie 6 months of Leuprorelin acetate before and during radiotherapy) will reduce risk of return of the cancer, either within the prostate region or at remote sites in the body, and prolong life. An additional goal is to see whether 18 months of bisphosphonate therapy (bone density therapy) using zoledronate will reduce the risk of cancer returning in the bones as well as stopping dangerous bone thinning which can sometimes be caused by hormone therapy. The trial also seeks to determine whether the additional therapy given in this trial alters quality of life.Read moreRead less
This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients ....This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients (>95%) is restrained to assure only a small proportion risk developing severe reactions. If one could predict which individuals were more susceptible to these reactions, then their large dose could be lowered to avoid the problem, and importantly, the dose could be increased for the majority of the patients, which would lead to a higher cancer cure rate. There are over 130 genes involved in repairing DNA. We hypothesize that dysfunctional DNA repair molecules are likely candidates to cause radiosensitivity in these individuals. In fact, a few of these genes have already been found to cause radiosensitivity, but we aim to assess all of the DNA repair genes in samples from patients that have had severe reactions to radiotherapy. Here we will use biospecimens, unique to our study and obtained from clinically radiosensitive cancer patients. We will use very sensitive, state-of-the-art procedures to test RNA and protein levels in our patients' cells and the latest technology to test what happens when candidate DNA repair molecule levels are altered. Additionally, we will determine the changes in DNA repair molecule numbers in response to different doses of radiation. We anticipate that results from these experiments will lead to the development of a clinical assay to test the likelihood of an individual having a severe reaction to radiotherapy, thus allowing individualization of treatment and, reducing radiotherapy side effects ultimately increasing cancer cure rates.Read moreRead less
The Trans Tasman Radiation Oncology Group is an experienced research group conducting cancer clinical trials involving radiotherapy (RT) in order to improve cure rates, quality of life and to reduce side-effects of treatment. Fifty per cent of all cancer patients need RT as part of their treatment. The aim of the proposal is to strengthen the quality and safety of RT trials by (a) enabling rapid review and checking of treatment by electronic means and (b) improve trial design.
C-myb Regulates Stem-progenitor Cell Cycle Entry In Colonic Crypts Providing Insights Into Colo-rectal Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
During a human's life time the colon or large bowel produced an extraordinary volume of cells. This requires almost unimaginable numbers of cell divisions. We are investigating the role of a gene (c-myb) that we propose is one of the key regulators of normal colon growth and function. It is expressed in the base of the functional unit of the colon called the colonic crypt. The base contains the stem cell population which give rise to all the crypt cells. We have generated and gathered a unique a ....During a human's life time the colon or large bowel produced an extraordinary volume of cells. This requires almost unimaginable numbers of cell divisions. We are investigating the role of a gene (c-myb) that we propose is one of the key regulators of normal colon growth and function. It is expressed in the base of the functional unit of the colon called the colonic crypt. The base contains the stem cell population which give rise to all the crypt cells. We have generated and gathered a unique and comprehensive set of mutant mice that have various degrees of dysfunction of the c-myb gene. We will study the colons of these mice to determine how c-myb regulates cell growth. We will also investigate these mice under stress conditions like that associated with cancer therapies like radiation treatment. Understanding such genes will improve the management of cancer patient how suffer gastro-intestinal side effects such as diarrhoea, perhaps hyper-proliferative disorders like inflammatory bowel disease and finally colon cancer where complete loss of cell growth is a feature.Read moreRead less
Australasian Leukaemia Lymphoma Group (ALLG) National Leukaemia And Lymphoma Tissue Bank (NLLTB)
Funder
National Health and Medical Research Council
Funding Amount
$2,106,750.00
Summary
Recent advances in knowledge about how cancer differ from normal cells, why some people are susceptible to cancer, and how new treatments can target cancer have all occurred through research on cancer cells from patients. To benefit patients with cancers of the blood and the immune system, we established a National Leukaemia and Lymphoma Tissue Bank in 2002. It is proposed to dramatically expand its size, add relevant clinical data, and streamline access and utility for Australian researchers. U ....Recent advances in knowledge about how cancer differ from normal cells, why some people are susceptible to cancer, and how new treatments can target cancer have all occurred through research on cancer cells from patients. To benefit patients with cancers of the blood and the immune system, we established a National Leukaemia and Lymphoma Tissue Bank in 2002. It is proposed to dramatically expand its size, add relevant clinical data, and streamline access and utility for Australian researchers. Ultimately, this will lead to better treatment and prevention of blood cancers.Read moreRead less
A Prospective Single Arm Trial Of Involved-field Radiotherapy For Stage I-II Low Grade Nongastric Marginal Zone Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$363,869.00
Summary
This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT ly ....This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT lymphomas, but the association has never been prospectively studied. Chlamydia Psittaci infection can cause MALT lymphoma in the orbit. The management of localised MZL outside the stomach is controversial and there have been no large prospective studies of any of the commonly-used treatments (radiotherapy, chemotherapy, surgery). No prospective studies have looked at the role of infection with Helicobacter pylori or the role of autoantibodies in these diseases. Radiotherapy is the best-characterised therapy in the literature and appears to have a high cure rate with low toxicity. The disease seems exquisitely radiosensitive. Management of localised MZL in Australia can be ad hoc and we have often seen patients who have undergone unnecessary mutilating surgery or ineffective chemotherapy. It has been reported that localised non-gastric MZL (stage I and II) can be cured with radiotherapy in a high percentage of patients (usually >70%) in retrospective studies from large centres such as Princess Margaret Hospital in Toronto. Workers from that centre will participate in this study. This study will: Prospectively report efficacy and toxicity for radiotherapy in MZL for the first time Definitively document Helicobacter Pylori status in all cases and Chlamydia status in orbital cases Provide a gold standard against which to compare new therapies This study won the award for the most highly supported study in its year at the TROG annual scientific meeting.Read moreRead less
Predictive Significance Of Tumor Hypoxia In Patients With Head And Neck Cancer Treated On A Randomized Trial
Funder
National Health and Medical Research Council
Funding Amount
$512,931.00
Summary
Some patients who receive chemotherapy and radiotherapy for head and neck cancer are not cured because their cancer cells are starved of oxygen that limits the ability of the chemotherapy and radiotherapy to kill the cancer cells. In this research project we will determine if measurement of low oxygen in the cancer will predict response to a novel cancer drug tirapazamine that selectively kills cells that are starved of oxygen. Low oxygen will be assessed by special scans, blood tests and by per ....Some patients who receive chemotherapy and radiotherapy for head and neck cancer are not cured because their cancer cells are starved of oxygen that limits the ability of the chemotherapy and radiotherapy to kill the cancer cells. In this research project we will determine if measurement of low oxygen in the cancer will predict response to a novel cancer drug tirapazamine that selectively kills cells that are starved of oxygen. Low oxygen will be assessed by special scans, blood tests and by performing molecular tests on cancer specimens. Success in this project may mean that we can identify patients who will most benefit from this treatment.Read moreRead less
New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and manageme ....New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and management that can reduce risk and improve patient survival.Read moreRead less
Proteomic Screening For Apoptotic Markers In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell li ....The induction of apoptosis, or programmed cell death, is a key factor in the response of tumours to chemotherapeutic agents and ionising radiation; therefore biological markers that predict the clinical outcome to these therapies are needed. Over the past 2 years, our laboratory has developed techniques of protein analysis to evaluate changes in proteins during apoptosis caused by chemotherapeutic agents. Preliminary protein profiling studies of apoptosis induction in human breast cancer cell lines showed time-dependent decreases in two proteins, identified as S100A6 and ubiquitin. Both are known to be important in cell function. In the proposed project we will build on our preliminary findings to provide important new information central to the understanding of cancer cell biology and apoptosis in addition to evaluating the ability of anti-cancer treatments to induce apoptosis. Using a combination of protein analysis technologies, this project has the potential to provide reliable and novel biomarkers which will indicate the efficacy and selectivity of anti-cancer treatments in inducing tumour cell death. The knowledge gained in this project will aid clinical assessment of the response to cancer treatment(s) in patients in the form of specific screening assays, and may result in identification and development of effective new agents for cancer treatment and prevention. Furthermore, the outcomes of this project will increase our understanding of fundamental cancer cell biology and apoptosis.Read moreRead less