A team of medical oncologists appointed by the University of WA and based at Sir Charles Gairdner Hospital is undertaking two medical trials which could result in improved treatments for people with mesothelioma.
One trial involves the combination of three chemotherapy drugs which is hoped to result in an improved immune function for patients, with little change in side effects compared with conventional chemotherapy treatment. The second trial, which got underway in 2010, is based around laboratory tests on mice which showed the use of immunotherapy drugs, in combination with chemotherapy, could reduce the size of mesothelioma tumours.
Professor Anna Nowak, a consultant medical oncologist at SCGH, who is a key researcher in both trials, said the trials would involve a small number of people and would potentially be expanded if there were indications that they could help people with mesothelioma.
Mesothelioma is a rare form of cancer of the protective lining that covers many of the body’s internal organs, the mesothelium. It is almost always caused by exposure to asbestos and is most commonly found in the pleura – the outer lining of the lungs and internal chest wall.
Professor Nowak said only six to eight years ago there was no treatment for mesothelioma which improved life expectancy. Chemotherapy treatment being offered at SCGH by Professor Nowak and colleague, Professor Michael Byrne, previously offered the most hope. A combination of chemotherapy drugs called cisplatin and gemcitabine were used to treat mesothelioma, though they decreased the size of tumours, patients also experienced side effects.
A large trial conducted in the United States showed a new chemotherapy drug, pemetrexed (brand name Alimta) was not only improving patients’ lung function and quality of life, but increased life expectancy by up to three months. Three months is a significant increase for mesothelioma patients who are given an average life expectancy of nine months from diagnosis of their disease.
“The Alimta only needs to be given once every three weeks, so it is given less frequently and has fewer side effects. People are less likely to run into problems with lowered blood counts and are less likely to have infections from lowered immunity caused by the treatment,” she said.
“When you add three months to nine months, that looks a lot better for patients – it means they are living 25 per cent longer from diagnosis.”
Professor Nowak, who has been involved in research in North America and was based in Chicago last year, said the first Perth trial involved the standard treatment of cisplatin and Alimta, with the addition of a low dose tablet chemotherapy.
“We are using a different sort of chemotherapy treatment in this trial,” she said.
“We are using it as a low dose, continuous tablet in combination with normal chemotherapy treatment,” she said.
Professor Nowak explains that there are immune cells in our body that fight cancer and there are immune cells that suppress the cells that fight cancer. The cells that suppress the cancer fighting cells are called regulatory T cells. She said patients with mesothelioma have more of these regulatory T cells, thereby preventing them from fighting the mesothelioma invading their lung tissue.
In laboratory trials on mice done in Perth, the low dose tablet drug treatment was shown to suppress these regulatory T cells – giving the cancer fighting cells a better chance and shrinking the tumours. The second trial is based on work in a laboratory on mice and as Professor Nowak explains, laboratory trials are not always replicated in human patients.
The trial, which will involve only about 15 patients from Australia, is a phase one trial and is the first time that this combination of immunotherapy treatment and chemotherapy treatment have been used in combination to treat mesothelioma. In further laboratory studies on mice, when the immunotherapy drug treatment was combined with chemotherapy, many mice were actually cured of mesothelioma.
“This was an exciting finding and we worked very hard to get the trial up and running in Perth to give our patients the opportunity to be involved in a trial that may help them,” she said.
“Once we have demonstrated safety in this trial, we will be looking to see if the combination of immunotherapy treatment and chemotherapy treatment works better in fighting the disease than just chemotherapy alone,” she said.
“With a small number of people it is not possible to say for sure. If we get an interesting signal and it is safe we will be looking at expanding the trial to an Australia-wide or, possibly, an international study.”
Measuring the size of mesothelioma tumours is very challenging because of the nature of the disease and where it forms in the lungs.
“If we want to bring an immune treatment we need to be able to tell whether it is working or not and that involves measuring the tumour on CT scans to assess whether it is shrinking.
“It might sound easy but with mesothelioma it is not simple, because of the way it grows. Shrinkage needs to be measured and proved it is getting smaller by substantial amount through combination of CT scans, xrays and blood tests.”
By Wendy Pryer