KEY POINTS:
Many cancer therapies of the future are expected to be highly successful in a narrow range of patients.
After decades of developing chemotherapies that aim wide, ever more finely "targeted" treatments are now the hottest trail for cancer researchers.
More than a dozen drugs aimed at about four
signalling pathways in cancer cells are in clinical trials. Some are becoming established treatments, such as Herceptin for breast cancer.
Another targeted cancer medicine is Tarceva, credited with saving the life of Auckland woman Anne Owen.
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Dr Richard Sullivan, the Auckland District Health Board's clinical director of medical oncology, said that although Tarceva and a similar drug, Iressa, had mixed results in trials, they worked fantastically well in some patients, possibly 10 per cent of those with lung cancer.
Those they helped most tended to be Asian women who had never smoked, who had a certain type of lung cancer, called adenocarcinoma, and two particular gene mutations.
Mrs Owen, who turns 56 this week, does not smoke, although she was exposed to secondhand smoke when young. She has adenocarcinoma but is Pakeha, not Asian and it is not known whether she has the gene mutations.
She had only days to live before starting Tarceva in September. An MRI scan soon afterwards showed no trace of cancer and Dr Sullivan said it had "melted away".
Dr Sullivan also cites the case of another patient, a non-smoking Asian woman with advanced lung cancer.
"She had had three lines of chemotherapy and had weeks to live. She responded to Iressa for 22 months before progression [of cancer]. She went on to treatment in 2003 and has had three years more of life because of Iressa."
She was now dying, having radiotherapy for palliative care. Iressa's manufacturer, AstraZeneca, paid for her to have the drug.
Dr Sullivan would like expensive medicines such as Tarceva - Mrs Owen pays $4500 a month in the private health sector - to be state-funded for the group for which they work. He suggests Pharmac or drug companies consider funding patients to receive a drug initially for a month to see if it works.
But Pharmac committees have already rejected an application to pay for Tarceva for patients with advanced lung cancer.
Money aside, Tarceva and Iressa are among the best hopes in a disease whose outlook is hopeless for many. For Dr Sullivan, the brightest hope is Avastin, another targeted therapy that works against several types of cancer.
A lung cancer breakthrough in Auckland has been the discovery of the drug called DMXAA, which is being tested against a range of cancers.
Dr Sullivan said it was an incredibly promising drug.
Most people diagnosed with lung cancer can expect to be dead within a few years.
After five years, only 5 to 8 per cent of the 1600 new cases annually are alive. Compare this with breast cancer patients, of whom around 70 per cent will be alive, or bowel cancer, around 50 per cent. Lung cancer was by far the leading cause of New Zealand male cancer deaths in 2002, although the annual incidence of the disease is declining, probably reflecting decades of declining smoking rates.
Smoking causes most lung cancer. Even secondhand cigarette smoke can cause the disease. Just under a quarter of people smoke, down from more than 35 per cent in the 1970s. Male and female rates are now similar but males have come off a higher level historically.
Dr Sullivan suggests the rising female rate of lung cancer may be from passive smoking. "A lot of those [women] have been brought up in smoking households or have lived with husbands who smoked."
Surgery, drugs and radiation therapy are used to treat lung cancer depending on the type of cancer and how far it has spread. In three out of four cases the disease has spread too far by the time the patient seeks help for surgery to be considered worthwhile. Access to newer chemotherapies improved markedly in 2001 when a "basket" of drugs became uniformly state-funded nationally, but access to the even newer targeted therapies is poor.
Results of a lung cancer trial of DMXAA were released this month. The trial, including patients at Auckland Hospital, found that giving the drug with chemotherapy increased median patient survival to 14 months, from 8.8 on the chemotherapy alone.
"It's an extremely promising performance," said Dr Bruce Baguley, co-director of the Auckland Cancer Society Research Centre, which developed the drug.
DMXAA is designed to destroy the blood supply of tumours. Avastin is also aimed at the blood supply, but at preventing the formation of new blood vessels, which tumours need to grow and spread.
Avastin, Tarceva, Iressa and Herceptin are all thought to work by blocking various protein-based signalling pathways that promote growth of either cancer cells or (with Avastin) blood vessels.
When a tumour becomes large enough to need its own blood supply, rather than just relying on oxygen from nearby tissue, it releases a protein that stimulates blood vessels to grow towards it. Avastin is thought to block this process.
Last month, Avastin was registered in the United States for use with a certain type of lung cancer which had spread within the chest, recurred or spread throughout the body.
This followed results from an advanced trial showing that those given Avastin with chemotherapies had a median survival of 12.5 months. Those who received just the chemotherapies had a median survival of 10.2 months.
This is considered a big advance. The US National Cancer Institute, which sponsored the trial, said it showed drugs such as Avastin were making important contributions in improving survival rates.
Avastin is made by Roche, the manufacturer of Herceptin. Both are extremely expensive.
"My belief, but I have no data to support this," said Dr Sullivan, "is that once you've picked out the group in which these drugs work [Avastin and Tarceva, for example], you will transfer them into early stage disease and start curing people, just like you did with Herceptin."
How new cancer treatments work
Until about 1995, most cancer drugs worked by attacking cell DNA.
These generally impaired cell division, effectively targeting fast-dividing cells. But they affected both healthy and cancerous cells.
These drugs are still being refined to improve their effectiveness while lowering the side-effects.
But technological advances and years of research have allowed scientists to zoom in even closer on the mechanics of many cancers. Various targeted therapies have emerged, holding the promise of harming fewer normal cells, reducing side-effects and improving quality of life.
One such therapy is a new class of drugs designed to disrupt the blood system. They exploit the differences between normal blood vessels and those that form to nourish tumours. They destroy the tumour's existing blood supply, starving it to death. Normal blood vessels are left unharmed.
Other drugs such as Avastin work differently, preventing new blood vessels from forming to nourish the tumour.
Several agents are now in clinical trials, including the Auckland Cancer Research Centre's drug DMXAA. Combined with chemotherapy, this has had positive results in Phase II trials in prostate, breast and lung cancer patients.
DMXAA acts directly on cells that line the interior surface of a tumour blood vessel, causing it to die. The drug also causes the release of a blood-clotting protein within the tumour vessel, causing a blockage.
In addition, the drug triggers the release of a compound that ultimately causes the death of the tumour.
UK biotech firm Antisoma, which holds the licence for DMXAA, is about to begin Phase III trials - the last step before registration as a medicine.
- Errol Kiong
