By Wilson da Silva
SIX YEARS ago, neurosurgeon Andrew Kaye would have given his patient 36 weeks to live. Today, after brain surgery, radiation therapy and firing lasers into the man’s head, the same patient is still visiting the Melbourne medic.
Such is the promise of photodynamic therapy, a little-known branch of medical science that uses lasers and sensitiser dyes and which is exciting oncologists around the world. Professor Kaye, at Melbourne University’s Department of Surgery at the Royal Melbourne Hospital, is on the leading edge of its application on brain tumours and is one of a host of scientists working to refine it for general application against the scourge of cancer.
Central to the therapy are specially-designed sensitiser dyes which are harmless when injected into patients. They drain from normal tissue in the body by the second or third day after injection but – probably due to the poor drainage system in tumours – remain soaked inside tumour tissue and even within individual cancer cells.
When irradiated with particular wavelengths of laser light, the dyes turn nasty. Chemical reactions ensue, releasing lethal elements that react with lipids on the surface of tumour cells lying in the laser’s path, rupturing them open and killing the tumour. As the dyes mostly drain from normal tissue, there is little ‘collateral damage’.
Photodymanic therapy has been tested on skin, bladder, uterus, eye and bowel cancers, achieving tumour reductions of between 50 to 100 per cent. A group in Britain, led by Professor David Phillips of London’s Imperial College and University of London colleague Professor Stephen Brown, has used lasers and dyes to destroy tumours in mice, rats and rabbits since animal trials began late last year. Clinical trials on humans have now begun in Britain and results are expected around mid-1993.
On a recent lecture tour of Australia and New Zealand, Phillips told 21C the therapy is safer, cleaner, quicker and cheaper than using radiation and has applications in dentistry, in unblocking clogged arteries and in more rapid diagnosis of a number of ills. Phillips’ dyes, developed over the past eight years, have successfully killed tumours in the pancreas of animals, he said.
“It destroyed pancreas tumours totally,” Phillips said. “Some normal tissue was also killed but some normal tissue was also regenerated.”
Based on his research, Phillips said the technique would probably be applied to tumours in the bladder, colon, breast, brain and surface tissue, but not lung cancer.
Kaye has concentrated on brain tumours, and began researching the therapy in 1984, treating his first patients two years later. The veteran of neurosurgical training in London and Cleveland now leads a team of 10 local and international scientists pushing back the frontiers of the technique.
Most brain tumours in adults are malignant -- standard treatment is to surgically remove the visible tumour and then blast the target with radiation in the hope of killing off what is left behind. But even then, the average survival rate is 36 weeks after treatment, he said.
“It’s terrible. Although we can remove all the tumour we can see, there is still the roots of the tumour that are left, and these are growing a long way, deeply into the brain,” Kaye said from his rooms at the Royal Melbourne Hospital. “It’s not possible to remove the roots of these tumours without destroying very important areas of the brain, just as it’s not possible to remove the roots of a tree without disturbing the soil.”
With photodynamic therapy, the bulk of the tumour is surgically removed as normal, and while the skull is still open, lasers fired into the region around the tumour base, activating tumour tissue soaked with the sensitisers. About 600 people die in Australia annually from cerebral glioma, the most common form of adult brain tumour.
The therapy is still experimental, and the much work needs to be done on developing more potent dyes, or making dyes that are activated by higher laser wavelengths which more easily penetrate tissue. Nevertheless, some 2,000 people have been treated with photodynamic therapy around the world and Kaye, who has treated more than 100 patients, says it is prolonging lives: “At the moment we have a median survival of two years, but we also have patients who have survived longer than two years.”
But the therapy is not a cure. Kaye’s team is in ‘phase two’ of trials into the therapy – treating people as they come and following up their cases. Before Kaye can say the therapy is a complete success, more rigorous trials would be needed in which one group of patients was treated with photodynamic therapy and the other not.
“Patients come to me for the treatment, and it’s very hard to tell them ‘no, I’m not going to give you the treatment’,” Kaye said. “Secondly, we’re all the time trying to develop better techniques, so if we start upon a ‘phase three’ trial, we’re stuck with using old techniques until we finish it, which may take two to three years.”
For throat and superficial bladder cancer, some ‘phase three’ trials have already begun in North America.
Kaye started with $10,000 of funding, and is now running the ground-breaking studies with an annual $400,000 budget. His group is backed by the Anti-Cancer Council of Victoria, the National Health and Medical Research Council, the Stroke Research Foundation, Royal Melbourne Hospital, the Royal Australasian College of Surgeons and Melbourne University. But the process is labour intensive, the lasers used are expensive pieces of high-technology, and ‘phase three’ trials beyond the group’s resources.
His team, along with others around the world, is also trying to improve its lasers. At present it uses a gold-metal-vapour laser made in Australia and an imported argon-dye laser, and is about to take delivery of an innovative copper-bromide laser developed in Adelaide that allows flexibility in setting wavelengths.
“I’m cautiously optimistic that the survival has improved, and the treatment is working, but it’s not curing patients,” Kaye said.
It certainly isn’t. That same patient Kaye first treated in 1986 has recently developed a recurrence of the tumour. “After five years, you’d hope it was a cure. But on the other hand, you might say that’s been six years whereas he might have only lived 36 weeks.
“We have to improve the sensitiser and the light delivery system, and this can only happen by investigating the basic sciences behind photochemistry and laser physics,” Kaye said.
“The Nirvana of the treatment would be a dye that got into every cancer cell in the brain no matter where it was scattered, and a light that could penetrate the whole of the brain, and activate every cancer cell. That may never be achievable, or it may be,” Kaye said.
Phillips’s research, funded by a British cancer charity, has not been patented in the hope that it will be brought into commercial application quickly.
“We’d like to see these things get into the clinics as soon as possible,” Phillips said. “The sensitisers are not expensive to make, but realistically they are another three years away [from application].”
Photochemistry, the little-known branch of science from which the technique developed, has been around for a while: “It’s gone (through) somewhat of a resurrection in the last 10 years. It’s been discovered, forgotten and rediscovered a few times,” Phillips said.
Using light in medical treatment has been around since the 1880s, when physician Neils Finsen cured unsightly winter sores on the faces of tuberculosis sufferers by shining filtered light on them. He won a Nobel prize for the work.
Ironically for someone who works with coloured lasers, Phillips is colour-blind. “I never would have thought I would have earned a living from coloured light,” he said with a smile.