New use for old drug may offer fresh hope to cancer patients
March 10, 2016
Who says you can’t teach an old dog new tricks? It seems drugs that have been around for years can sometimes do something spectacular when applied in a whole new way.
Called ‘drug re-positioning’, the practice of using already approved drugs for new medical applications has already proven successful in the treatment of a number of diseases. Soon to be added to the list – if all goes according to plan – is a rare but deadly form of cancer called angiosarcoma, which affects the lining of blood vessels and can occur in any part of the body.
In a wonderful example of international collaboration and ‘bench-to-bedside’ research, a discovery made in an Australian research laboratory, further developed by scientists at a French university, then applied by clinicians at an Indian hospital, has generated extraordinary results in patients with advanced and inoperable angiosarcoma.
The research has been published in the new online journal EBioMedicine, led by the editors of Cell and Lancet.*
It all began in the Sydney laboratories of the Children’s Cancer Institute, where researchers found that a drug developed to treat high blood pressure, propranolol, has a powerful ‘chemo-boosting’ effect when used in combination with certain chemotherapeutic drugs for the treatment of angiosarcoma.
“We tested a number of drugs in our laboratory model of angiosarcoma, and were excited to discover that the beta-blocker propranolol made a huge difference to the anti-cancer effects of a chemotherapy drug called vinblastine,” explained Professor Maria Kavallaris, who worked on the project alongside colleague Dr Eddy Pasquier.
“Our earlier studies had shown that beta-blockers can work well with chemotherapy against some childhood cancers, as well as certain breast cancers. So we thought we’d see if something similar could be done with angiosarcoma.”
Once the team had shown that propranolol boosted the effects of vinblastine against angiosarcoma, Dr Pasquier worked with clinicians at the Tata Memorial Hospital of Mumbai and Aix-Marseille University in Marseilles to design a new treatment protocol. The new protocol was then used in a small pilot study in Mumbai to treat seven patients with advanced and inoperable angiosarcoma.
“The results of this pilot study were quite incredible,” said Dr Pasquier. “All seven patients responded. One ended up with no clinical signs of disease at all, and another two had their tumours regress to the point of almost disappearing. These are patients who had no prospects at all for survival beyond 12 months, and in whom the treatment was really just given as palliative care, so the fact that two of them are still alive today, up to 20 months later, shows just how effective this treatment is.”
These early findings are extremely encouraging. Now a larger trial needs to be done to confirm that this treatment can indeed improve patient outcomes, and is safe to use.’
Dr Pasquier and colleagues have recently secured funding for such a trial, and anticipate that if the results prove positive, the treatment could go on to become available to angiosarcoma patients all over the world.
According to Professor Kavallaris, a big plus of the new treatment is its low toxicity, which means it could be given in an outpatient setting. Even better, it is affordable. “This option is more efficient and also much cheaper than other experimental treatments for angiosarcoma, and so is far more accessible to developing countries,” she said. “We are really hoping it can contribute to what we call ‘a fair global oncology’.”
The team is also hopeful that, over time, the treatment will prove useful for a number of other cancers, including difficult-to-treat cancers in children.
* Pasquier E, André N, Street J et al. (2016). Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-Based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine (in press) doi:10.1016/j.ebiom.2016.02.026
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.