Prostate and kidney cancers are among the most commonly diagnosed worldwide. Research at Western Sydney University into the latest treatment is improving the quality of life and increasing survival rates of patients with incurable forms.
Kidney cancer (renal cell cancer) accounts for two to three per cent of all cancers and causes 144,000 deaths annually worldwide. Although recent advances in the understanding of the molecular mechanisms underlying kidney cancer have led to the development of targeted therapies for this disease, up to 30 per cent of patients have secondary cancers — known as metastases — at the time of initial diagnosis and fewer than 10 per cent survive more than five years.
Prostate cancer, meanwhile, is a leading cause of cancer-related deaths in men. When confined to the prostate gland, the five-year survival rate is almost 100 per cent, but when the tumour spreads or stops responding to first-line hormone therapy, the survival rate drops considerably. Metastatic castration-resistant prostate cancers (MCRPC) are incurable and account for approximately 258,400 deaths annually worldwide.
For both these types there is a pressing need for improved treatment options.
The Medical Oncology Unit at WSU carried out two pivotal clinical trials confirming the efficacy of a drug called pazopanib for kidney cancer, and one called abiraterone for MCRPC. The trials also provided further safety data and identified additional types of patients that will benefit from treatment. The results, published in the prestigious New England Journal of Medicine, have led to more effective and safer treatment options for patients with kidney cancer and MCRPC all around the world.
Foundational Professor and Head of the Medical Oncology Unit at WSU, Paul de Souza, says: “It was a privilege to be involved in the large international collaborative efforts evaluating the efficacy and safety of these drugs, and to be able to provide patients access to newly developed treatments.”
Comparing safety profiles
de Souza and colleagues compared the effects of pazopanib to those of a previously approved kidney cancer drug, sunitinib. The trial involved 1,110 patients with the most common type of metastatic kidney cancer.
The drugs are very similar in terms of their mechanism of action: they both prevent tumours from forming new blood vessels, and halt cancer cell proliferation and survival by inhibiting the receptors for vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
The study, sponsored by GlaxoSmithKline, showed that pazopanib was as effective as sunitinib in helping patients survive.
A bonus finding was that patients on pazopanib had a lower incidence of side-effects including fatigue, soreness of the hands or feet, and soreness of the mouth, in comparison to sunitinib.
“When cancer drugs like pazopanib and sunitinib show similar survival benefits, other drug factors, like safety and quality of life, assume a greater importance,” says de Souza. “Our clinical studies are helping to optimise the use of these drugs. Refining the drug dose and schedule, as well as identifying those patients that are most likely to respond will ensure we maximise the benefits and minimise the risk of newly approved therapeutics.”
At present, pazopanib and sunitinib are among the first-line treatment options for patients across the world with inoperable kidney cancer or metastatic kidney cancer.
Need to know
- A clinical trial of a kidney cancer drug shows it works with fewer side-effects than a similar drug
- A clinical trial of a prostate cancer drug shows it is as safe and effective as a chemotherapy alterative
- WSU research has improved the quality of life of cancer patients
Identifying a new patient group
A second clinical trial carried out by WSU investigators explored the potential benefits of drug called abiraterone in patients with MCRPC who had not undergone chemotherapy. Abiraterone is a potent and selective inhibitor of cytochrome P-450c17, a critical enzyme for the production of male hormones. It was originally approved by the US Food and Drug Administration (FDA) for the treatment of patients with MCRPC who received prior chemotherapy containing docetaxel.
This study, funded by Janssen Pharmaceuticals, involved 1,088 patients receiving abiraterone acetate plus the immunosuppressant drug prednisone, or a placebo plus prednisone. The abiraterone–prednisone combination improved patient survival and significantly delayed clinical decline and the initiation of chemotherapy compared with prednisone alone. Furthermore, patients receiving abiraterone were pain-free for longer and had better quality of life.
The results showed that abiraterone works as well and is as safe as docetaxel chemotherapy and have led to the drug being made available to patients earlier in the course of their treatment. Abiraterone is now used globally in men with incurable, advanced prostate cancer after failure of hormone therapy both prior to and after first-line chemotherapy.
Abiraterone and pazopanib are now approved by Australia’s Therapeutic Goods Administration and are listed on the Pharmaceutical Benefits Scheme, meaning that many Australians with MCRPC or kidney cancer have access to these medications at reduced costs.
“Given the high incidence of renal cell cancer and MRCPC worldwide, the discovery of better-tolerated drug interventions, such as pazopanib, or of durable responses in a new patient group, as in the case of abiraterone in patients prior to chemotherapy, has a significant impact on patients’ quality of life and survival,” says de Souza.
WSU’s Medical Oncology Unit works closely with local hospitals to conduct both early human studies and late-phase clinical trials to get the best, most innovative treatments to cancer patients faster. By working at the interface of academia, industry and healthcare, de Souza and colleagues are able to accelerate the translation of cancer research into new options for front-line therapy. WSU’s commitment to embed research into healthcare creates a unique and attractive setting for students, physicians, researchers and patients alike.
Meet the Academic | Professor Paul De Souza
Professor Paul de Souza has been a practicing medical oncologist for over 25 years, having obtained the FRACP in 1992. He trained in medical oncology at St George and Prince of Wales Hospitals, and was Research Assistant Professor at the University of Virginia (1994-1997) before returning to Wollongong and St George Hospitals as a staff specialist (1997-2010).
In 2011, he was appointed Foundation Professor of Medical Oncology at Western Sydney University and a Conjoint Professor, UNSW. He has sub-specialty interests in genitourinary cancer, brain cancer and rare cancers such as sarcoma. He is currently the Director of CONCERT, a NSW Cancer Institute funded Translational Cancer Research Centre, Director of a cancer research laboratory at the Ingham Institute, Liverpool, Director of the Phase I trials unit at Liverpool Hospital, and oncology program director for Western Sydney University Medical School. In the past, he has served in executive positions for the Medical Oncology Group of Australia (MOGA) and the Specialists Advisory Committee in the Royal Australian College of Physicians for Medical Oncology. He has been teaching medical students, JMOs, registrars and advanced trainees over many years; he continues to supervise research and PhD students.
Higher Degree Research at Western
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Future-Makers is published for Western Sydney University by Nature Research Custom Media, part of Springer Nature.