A Clinical Trial To Determine The Optimal Timing Of Androgen Deprivation In Relapsed Or Non-curable Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$627,600.00
Summary
The aim of the study is to clarify when is the optimal time to start hormone treatment for men with certain stages of prostate cancer. It has long been known that testosterone removal impedes prostate cancer growth, although not permanently. The removal of testosterone, however, has side effects , including loss of libido, hot flushes, weight gain, and in the longer term osteoporosis, loss of muscle bulk and mental changes such as loss of memory. Any benefit to be gained for a patient must there ....The aim of the study is to clarify when is the optimal time to start hormone treatment for men with certain stages of prostate cancer. It has long been known that testosterone removal impedes prostate cancer growth, although not permanently. The removal of testosterone, however, has side effects , including loss of libido, hot flushes, weight gain, and in the longer term osteoporosis, loss of muscle bulk and mental changes such as loss of memory. Any benefit to be gained for a patient must therefore be weighed against these side effects. This is particularly relevant in situations in which cure is not possible, when the aim of treatment should be to manage symptoms (either by preventing or delaying them or treating them as they arise). There are two situations in which a man may be diagnosed as having active prostate cancer but be without symptoms requiring immediate treatment. The first is after the failure of curative treatment, shown by the presence of prostate specific antigen (PSA) in the blood, but without any other evidence of prostate cancer. The second is a man newly diagnosed with asymptomatic prostate cancer, but with other reasons (such as heart disease) which make an attempt at cure inappropriate. We do not know in either case whether or not men live longer if treatment is started immediately, or whether it is reasonable to wait until symptoms develop, thus potentially postponing the side effects of treatment. The trial will therefore include these two groups of men. Half the men will be randomised to receive immediate treatment, and half to treatment starting when symptoms develop, or when there is evidence of progressive disease. The main endpoint is overall survival, balanced against quality of life and side effects from the disease and treatment. The hypothesis is that early treatment will improve survival with acceptable effects on quality of life.Read moreRead less
BMP4 - A Metastasis Suppressor Gene In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$454,220.00
Summary
Breast cancer is the most common cause of cancer death in western women. Whilst the primary tumour can often be eradicated successfully, in many cases, it may have already spread to other organs, including lungs, liver and bone, causing severe morbidity. Current treatments are largely palliative and new therapies that specifically prevent to spread of breast cancer are urgently required. However, little is known about the molecular pathways regulating the spread of cancer cells. We have shown th ....Breast cancer is the most common cause of cancer death in western women. Whilst the primary tumour can often be eradicated successfully, in many cases, it may have already spread to other organs, including lungs, liver and bone, causing severe morbidity. Current treatments are largely palliative and new therapies that specifically prevent to spread of breast cancer are urgently required. However, little is known about the molecular pathways regulating the spread of cancer cells. We have shown that expression of a gene called BMP4 in tumours blocks the spread of breast cancer in a mouse model. The aim of this project is to develop the application of BMP4 as a therapy for advanced breast cancer using our mouse model. We will measure the expression of BMP4 in human breast cancer and test whether treatment with purified BMP4 protein can protect mice from the spread of breast cancer. If successful, this study will offer a new therapy for women with currently incurable breast cancer.Read moreRead less
A Clinical Trial Evaluating Neoadjuvant Chemotherapy For Women With Large Operable Or Locally Advanced Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$269,805.00
Summary
Larger operable and locally advanced breast cancers (BC) which can involve the skin of the breast and lymph nodes under the arm are associated with poorer survival. Standard treatment usually includes neoadjuvant (or preoperative) chemotherapy to try to reduce the size of the cancer, followed by surgery and radiation therapy to treat any remaining cancer in the breast. Many women, despite maximum treatment, will still die from their disease, hence the need to develop more effective drug therapie ....Larger operable and locally advanced breast cancers (BC) which can involve the skin of the breast and lymph nodes under the arm are associated with poorer survival. Standard treatment usually includes neoadjuvant (or preoperative) chemotherapy to try to reduce the size of the cancer, followed by surgery and radiation therapy to treat any remaining cancer in the breast. Many women, despite maximum treatment, will still die from their disease, hence the need to develop more effective drug therapies. The advantages of neoadjuvant chemotherapy include: the potential to reduce the size of the breast cancer which may allow breast conserving surgery rather than mastectomy; and, the ability to directly assess the response of breast cancers to new drug treatments. This new research project aims to evaluate standard chemotherapy (epirubicin and cyclophosphamide) followed by a course of two newer, possibly more beneficial, chemotherapy drugs for breast cancer (docetaxel and gemcitabine (DG)) followed by surgery, in women with large operable-locally advanced breast cancer. The trial will allow patients with HER2 positive breast cancer to receive trastuzumab (Herceptin ) in addition to the DG chemotherapy treatment cycles. The study will measure the tumour response rates, efficacy and safety of the proposed treatments. Patients will be asked to consent to an extra core biopsy and a small sample of their breast tissue collected at the time of their breast surgery to be used for research to help better understand the biology of the disease and responses to treatment. The study could plausibly offer a better treatment for patients, resulting in a better prognosis for women who present with large operable or locally advanced breast cancer. The trial will be conducted, in Australia and New Zealand, by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG) and will involve approximately twenty Australian hospitals.Read moreRead less
The Breast Cancer Biospecimen Resource will consist of stored samples of the majority of newly diagnosed breast cancers in NSW and through the Australian and New Zealand Breast Cancer Trials Group together with accurate, prospectively tracked clinical data on each specimen. This facility will serve as a model for extension of similar procedures to other common Australian cancers including cancers of the lung, bowel, prostate and melanoma. Research that is facilitated by this Resource holds real ....The Breast Cancer Biospecimen Resource will consist of stored samples of the majority of newly diagnosed breast cancers in NSW and through the Australian and New Zealand Breast Cancer Trials Group together with accurate, prospectively tracked clinical data on each specimen. This facility will serve as a model for extension of similar procedures to other common Australian cancers including cancers of the lung, bowel, prostate and melanoma. Research that is facilitated by this Resource holds real promise for improving patient selection for treatment. This will return a significant humanitarian and cost saving benefit. In addition this advance would also maximise the benefit of population mammographic screening.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
mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patien ....mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patients was observed. This project will provide mechanistic details of involvement of mTOR signalling in pathogenesis of the serous ovarian carcinoma, and develop a rationale for targeting mTOR pathway in these patients. Read moreRead less
Total Laparoscopic Hysterectomy (TLH) Vs. Total Abdominal Hysterectomy (TAH) For The Treatment Of Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$809,860.00
Summary
The LACE study is a clinical trial comparing two types of surgery for women with early-stage cancer of the inner lining of the uterus, known as endometrial cancer. Treatment for endometrial cancer involves removal of the uterus, tubes, ovaries and lymph nodes. Traditionally this has been performed by open surgery via an abdominal incision. Open surgery is effective for endometrial cancer, but it is highly invasive, resulting in visible scarring, tissue damage, blood loss and a fairly high risk o ....The LACE study is a clinical trial comparing two types of surgery for women with early-stage cancer of the inner lining of the uterus, known as endometrial cancer. Treatment for endometrial cancer involves removal of the uterus, tubes, ovaries and lymph nodes. Traditionally this has been performed by open surgery via an abdominal incision. Open surgery is effective for endometrial cancer, but it is highly invasive, resulting in visible scarring, tissue damage, blood loss and a fairly high risk of complications. Laparoscopic surgery, commonly referred to as keyhole surgery, is a new approach to removing the uterus, tubes, ovaries and lymph nodes. Preliminary results from this less invasive surgery have been extremely encouraging. Laparoscopic surgery is practical and safe in treating endometrial cancer, while also resulting in less tissue damage, lower blood loss, less pain and a shorter recovery period in hospital. The LACE study aims to give definitive answers about the results offered by laparoscopic surgery in treating women with early stage endometrial cancer. The primary aim is to investigate whether the treatment of endometrial cancer using laparoscopic surgery is as good as that using open surgery. Secondary aims look at whether laparoscopic surgery provides more benefits compared to open surgery for endometrial cancer, such as: - improvements in the quality of life post-surgery, - reduced number of early and late surgery-related complications, - shorter stays in hospital, - fewer blood transfusions required, - less pain post-surgery, and hence fewer pain-killers. The LACE study is already under way, with recruitment on target for Stage 1. This application seeks funding for Stage 2, to expand recruitment from 2007. The outcomes of the trial will have a significant bearing on the future choice of treatment for endometrial cancer. Therefore the study will impact many patients around the world, including ~2000 women every year in Australia.Read moreRead less
Pathophysiology Of Oxaliplatin-induced Nerve Dysfunction And Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$281,255.00
Summary
When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been com ....When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been completed. The other chief problems encountered during chemotherapy can be overcome: nausea and vomiting can be treated; myelosuppression can be reversed. End organ toxicity such as neuropathy cannot be controlled. Despite the high incidence of neuropathy due to chemotherapy, the mechanisms involved remain poorly understood, particularly with newer therapies. The aim of the present study is to measure nerve function in oncology patients treated with oxaliplatin using a novel protocol, attempting ultimately to identify aspects of dysfunction that correlate with clinical abnormalities, so helping to pin-point the mechanisms responsible for neuropathy. Once identified, management strategies can be developed to better target the prevention and treatment of neuropathy in oncology patients treated with chemotherapy.Read moreRead less
The applicant's research is aimed at delineating the molecular mechanisms of action of steroid hormones in the pathogenesis of breast and prostate cancer with the goal of developing new diagnostic, prognostic and therapeutic response parameters of clinica