New class of drug holds out promise for sufferers

Margaret* was dying of lung cancer in 1999 and with nothing left to lose she agreed to take a new pill called Iressa (Gefitinib), which had just been developed to target this disease.

Today she is celebrating her "fifth Iressa birthday" after being "reborn". She has become a scuba diving enthusiast and is leading a full life.

Margaret was the first patient treated with this new class of anti-cancer drugs, known as Epidermal Growth Factor Receptor inhibitors, to reach the market in lung cancer.

Iressa spells new hope for victims of the biggest killer cancer in the world, with 120 new cases of lung cancer a year in Malta and the incidence in females on the increase.

This new drug was the topic of a clinical experience meeting, which was held last week in Athens, Greece and attended by The Times, to raise awareness on the disease and future treatment strategies.

Iressa, which has been hailed as a miracle drug by people like Margaret, does not have the same response rate among patients, according to details released by AstraZeneca, the pharmaceutical company which has developed this new cancer treatment.

AstraZeneca vice president George Blackledge told journalists that while the drug worked unbelievably well in some 15 - 20 per cent of those who tried it, it was not so successful with the remainder.

This had confounded researchers but two months ago there was a breakthrough discovery that revealed that a mutation in the patient's DNA makeup could explain why one person responded much better and quicker to the treatment and the other did not.

Dr Blackledge said the US Food and Drug Administration had already given the green light to the drug and AstraZeneca was now hoping it would be approved by the EU by the end of this year.

There is a Maltese representative on the EU committee deciding on Iressa and once approved AstraZeneca's sole distributors in Malta, Associated Drug Co. Limited, will start importing it.

Iressa, which comes in tablet form, is already being sold to patients in the US at $1,800 for a month's supply of 30 tablets.

At the moment lung cancer patients in Europe who failed chemotherapy treatment were benefiting through AstraZeneca's "compassionate use scheme".

Every country has equal access to this scheme and in Malta 10 patients with lung cancer and one person with head and neck cancer had been provided with the new drug.

Stephen Brincat, chairman and consultant at the radiotherapy and oncology department at Sir Paul Boffa Hospital, followed their development.

"The response rate in these patients was low and we witnessed minor responses. Of course, the spectrum varies from patient to patient and there are a minority who will get successively better," he explained.

Dr Brincat said Iressa had very little side effects, especially when compared to other forms of cancer treatment such as chemotherapy, which is associated with unpleasant side effects.

"I think this breakthrough is more exciting in the way it works rather than the response rate we have had. Iressa is one of a family of drugs which will be more active in the future," he said.

"One must not give in to the hype. There had been a lot of publicity on this drug, which raises people's hopes, but the reality can be different. Iressa started out with a lot of promise, which has so far not been realised.

"However, this shows that there will be some major changes in the way we treat cancer in the next few years," Dr Brincat said.

* Not her real name

Lung cancer facts and figures

¤ In Malta, lung cancer, once an exclusively male disease, is rapidly gaining ground in the female population, with an expected epidemic in the next 20 years, according to oncologist Stephen Brincat.

¤ Presently the male to female ratio of lung cancer in Malta is 6:1, compared to a ratio of 10:1 15 years ago.

¤ Lung cancer has a high mortality rate, of at least 80 per cent.

¤ There are two main types of lung cancer, classified according to the appearance of the cells under the microscope: these are non-small cell lung cancer (around 75 to 80 per cent of cases) and small cell lung cancers.

¤ The prognosis for lung cancer is poor. Overall the proportion of patients alive five years after diagnosis is approximately 15 per cent.

¤ Prognosis depends on how far the cancer has spread when it is first detected. If non-small cell lung cancer is found before it has spread to other organs, the five-year survival rate is about 15 per cent. However, few lung cancers are found at this early stage and it is normally diagnosed at the advanced stage.

¤ Smoking is by far the greatest risk factor, with up to 90 per cent of lung cancers thought to result from smoking. The risk declines when people quit the habit.

¤ Risk increases with age and lung cancer is fairly rare in people under the age of 45.

¤ Passive smoking and exposure to asbestos or radon (a radioactive gas that occurs naturally in soil and rocks) can increase the risk.

¤ Symptoms of lung cancer include persistent coughing, chest pain, coughing up blood, shortness of breath, wheezing or hoarseness, repeated pneumonia or bronchitis, weight loss and fatigue.

¤ There is no reliable screening test to detect lung cancer before the symptoms develop but researchers are working to develop such a test.

Iressa facts

¤ Iressa (Gefitinib) is the first in a new class of anti-cancer drugs known as Epidermal Growth Factor Receptor inhibitors to reach the market in lung cancer.

¤ It is a once-daily 250mg oral medication and is indicated for the treatment of advanced non-small cell lung cancer.

¤ AstraZeneca, which has developed Iressa, is currently the second largest company worldwide in sales of anti-cancer products.

¤ Iressa has been approved for the treatment of non-small cell lung cancer in 28 countries including the US, Japan, Australia and Canada and is currently undergoing regulatory review with other authorities worldwide, including Europe.

¤ It has been designed to block the activation of an intracellular signalling pathway implicated in cancer cell proliferation and survival in a variety of common tumours including non-small cell lung cancer.

¤ This pathway is triggered by the binding of a growth factor termed Epidermal Growth Factor to a receptor found on cell surfaces called the Epidermal Growth Factor Receptor. The activated EGFR then sends signals within the cell, via an enzyme called tyrosine kinase, which instruct the cell to grow and multiply.

¤ Iressa is a small molecule that passes into the cell and selectively blocks the EGFR tyrosine kinase enzyme, effectively "switching off" the signals transmitted from the EGFR. Therefore, Iressa has the potential to slow and reduce cancer cell proliferation.