Optimal Duration Of Neoadjuvant Androgen Deprivation Therapy In Localised Prostate Cancer Treated By Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$422,335.00
Summary
The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres acr ....The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres across Australia and New Zealand. It would not have been possible without the continuous funding support of the NHMRC. So far this trial has shown that AD does prevent prostate cancer from returning after radiotherapy. This is very important because the need for treatment of recurrent cancer (usually AD for the rest of the patient's life) is halved by 6 months AD compared to standard treatment (radiotherapy alone). However, it is now necessary to observe the patients in this trial for another 5 years to find out whether AD also prolongs life, and whether 6 months AD is more effective than 3 months. Further patient follow up is also necessary to identify whether some men respond better to treatment than others. This is very important because it will enable treatment to be tailored to individual patients, in particular those who require more treatment than is given in this trial. This funding application is therefore to enable patient follow up on this large scale trial for another 5 years.Read moreRead less
Optimal Duration Of Neoadjuvant Androgen Deprivation Therapy In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$275,000.00
Summary
Each year approximately 8000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation' [AD] therapy) can produce shrinkage of prostate cancer. In fact AD has caused temporary but valued relief to millions of men with cancer ....Each year approximately 8000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation' [AD] therapy) can produce shrinkage of prostate cancer. In fact AD has caused temporary but valued relief to millions of men with cancer of the prostate that has spread throughout the body for the last five decades, worldwide. It remains uncertain however whether AD administered before surgery or radiation will benefit any of the 8000 men each year who develop localised cancer by shrinking the cancer first. In 1996 a trial involving 800 men across Australia and New Zealand commenced under the auspices of the Trans-Tasman Radiation Oncology Group (TROG) to answer the questions: 1 - Does either 3 or 6 months AD prior to radiotherapy reduce the chances of recurrence of the cancer after radiotherapy? 2 - Does such therapy reduce the volume of tissue requiring radiotherapy and hence the chances of long term side effects after radiotherapy? This grant will support collection of follow-up information from the trial and hence answers to the questions asked.Read moreRead less
DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutat ....DNA methylation is a mechanism used by many organisms, including humans, to keep certain regions of DNA inactive, i.e. in a state where they will not be read. Errors in this process may result in inappropriate inactivation of a gene, termed epimutation; this may occur even when no DNA sequence changes (i.e. mutations) are present. Some individuals are born with high levels of an epimutation that predisposes them to developing multiple cancers. Little is known about whether low levels of epimutations (only a portion of the body's cells affected) are important in development of sporadic (common) cancer. The aim of this project is to determine the levels of epimutations in the normal tissues of healthy individuals, and compare these with the levels in normal tissues of people who have had certain types of cancers. In doing this we hope to find out if low level epimutations contribute to the risk of developing sporadic cancer.Read moreRead less
Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
Randomised Study Of Radiotherapy (RT) Or ChemoRT To Palliate Symptoms Of Advanced Oesophageal Cancer (OC)
Funder
National Health and Medical Research Council
Funding Amount
$236,375.00
Summary
Cancer of the oesophagus (gullet) causes swallowing problems (dysphagia) by narrowing the gullet and harming food movement to the stomach. >90% of patients with oesophageal cancer (OC) have dysphagia. OC is common, representing >1% of all cancer diagnoses, but is rarely curable, >80% of patients having disease beyond the oesophagus at presentation. Overall survival is thus poor with <10% of patients alive at 3 years. Most have disease obstructing the gullet and thus most patients suf ....Cancer of the oesophagus (gullet) causes swallowing problems (dysphagia) by narrowing the gullet and harming food movement to the stomach. >90% of patients with oesophageal cancer (OC) have dysphagia. OC is common, representing >1% of all cancer diagnoses, but is rarely curable, >80% of patients having disease beyond the oesophagus at presentation. Overall survival is thus poor with <10% of patients alive at 3 years. Most have disease obstructing the gullet and thus most patients suffer dysphagia as they come to terms with dying. This affects both the patient's ability to maintain nutrition and impinges on all areas of quality of life (QoL). Enjoying food is a pleasure of life and an inability to swallow food, water and saliva causes a significant loss of personal self esteem. Relief of dysphagia is the highest priority for treatment. This must be balanced against toxicity of treatment. It is surprising that patients and their doctors must consider this with very little scientific data to help their decisions. The trial uses a simple 2 arm randomisation, radiotherapy (RT) 35Gy in 15 fractions, versus the same with chemotherapy (Cisplatin and Fluorouracil). Both the RT schedule and chemotherapy are commonly used in Australia for this and other cancers. This is the first trial in the world to prospectively assess RT and the first to compare the effect of adding chemotherapy. The trial will:- 1. establish a new method of assessing dysphagia and QoL in all patients with OC using a set of specific questions(EORTC-QLQ-C30+oesophageal module). 2. quantify response and toxicity of a common RT schedule. 3. evaluate the extra benefit and toxicities of chemotherapy. 4. evaluate patient and tumour factors determining outlook, and response to treatment. 5. provide a bench mark for trials of new chemotherapy agents and different RT schedules. The trial will guide management and provide information for incurable patients even if both arms are similar in their effect.Read moreRead less