Chemists winning war on the Big C

A new cancer drug called Gleevac has created international excitement. KATHERINE HOBY looks inside the labs to see what else is brewing.

That dreaded C word: cancer.

Despite amazing advances in technology and medicine, cancer is still one word that strikes fear into our hearts.

It does so because however vigilant you are, or however healthy the life you live, you may still wake up one day to find yourself fighting the battle of your life.

The enemy within comes in many forms - including pancreatic, breast, melanoma, bowel, lung, liver - and at times seems to choose its victims indiscriminately. Everyone knows someone who has succumbed to it, or who is battling cancer now.

With heart disease, it is New Zealand's biggest killer, as in most parts of the world.

The race to find drugs to combat, repel and cure various cancers seems never-ending, and at times frustrating, but behind closed doors in laboratories, company offices and homes worldwide, war is being waged on cancer.

Recent reports have highlighted a drug, Gleevac, as a serious breakthrough in the treatment of chronic myeloid leukaemia.

Other drugs and treatments are in trials for other forms of the disease.

But, realistically, how good are these drugs? And are we any closer to curing cancer?

What is the story with Gleevac?

Journalists worldwide, including Time magazine, have leaped on Gleevac.

Medical professionals have been more cautious, saying the long-term results of the trials will have to be monitored.

But they, too, have been surprised and excited.

Gleevac (also known as STI-571, imanitib, Glivac) is a drug which operates by killing abnormal cells while having little effect on normal cell growth.

At this stage it has been tested on patients with chronic myeloid leukaemia only. Fifteen to 20 patients are diagnosed with this condition in Auckland each year. Overall, it affects one or two in 100,000 New Zealanders every year.

How effective is it?

Associate Professor of Haematology Peter Browett, of the Auckland Medical School, has been in charge of the New Zealand trials of Gleevac.

He says it is a dramatic step forward in cancer treatments.

Chronic myeloid leukaemia is a small player compared with other cancers, he says, but "for the first time we were able to target the enzyme causing the cancer."

Dr Browett describes that development as phenomenal.

World-renowned leukaemia authority Dr Moshe Talpaz has said it is "a dramatically active cancer drug, perhaps the most impressive drug that I have seen in 20 years as an oncologist."

Why are the experts so excited?

The success of Gleevac in trials worldwide has been excellent but, more importantly, it is the way the drug works that has everyone talking.

Gleevac operates by killing the abnormal cells while having little effect on normal cell growth. It was designed to be an inhibitor of an enzyme created by the Philadelphia chromosome, an abnormal chromosome found only in leukaemia cells.

Because this enzyme is found only in leukaemia cells, Gleevac does not appear to affect normal cells in the bone marrow and elsewhere in the body. This contrasts with many traditional anti-cancer drugs, which kill both cancerous and normal cells.

Experts hope it may act in a similar way against other cancers, or that they may be able to model different treatments on Gleevac and the way it works.

What are the trial results?

Trials started in 1998, with 31 out of 31 patients from the initial trial having their blood count return to normal.

In April this year, researchers reported results of the follow-up study in the New England Journal of Medicine: 53 of 54 patients had normal blood counts restored. The National Cancer Institute in America reports that 51 were still doing well a year on from the trial, and had only minor side-effects.

Over 500 patients with chronic myeloid leukaemia who had not responded to conventional therapy have now been treated with Gleevac. Over 90 per cent have seen their white blood cell counts and spleen size return to normal, and in nearly one-third the Philadelphia chromosome cannot be detected in bone marrow.

Four people in New Zealand are trying Gleevac. The results so far have been very promising, Dr Browett says.

Rotorua woman Carol Clarke has been on the drug for just over a year. She was profiled in the Weekend Herald on April 28.

After six months on Gleevac, the Philadelphia chromosome count in her bone marrow had fallen from 100 per cent to zero.

Could it be tried on other cancers?

Gleevac is already being used in trials overseas on other cancers.

The director of the United States National Cancer Institute, Dr Richard Klausner, says the institute, with drug company Novartis, is conducting clinical trials on Gleevac's possible effectiveness against other cancers, including glioma, soft tissue sarcoma and a rare kind of gastrointestinal cancer called gastrointestinal stromal tumour.

When will Gleevac be freely available?


The United States Food and Drug Administration approved Gleevac last month, after one of the fastest reviews for a cancer drug ever.

Government regulations permit the FDA to accelerate approval of certain new drugs that may offer a significant improvement in treating serious or life-threatening illnesses compared with current treatments.

At present, Gleevac is available here only to patients who are on the closed clinical trials. Results may be known this year, and Gleevac may be registered in New Zealand. It is not known exactly when it could be available, or what it may cost.

How does a drug get from laboratory to boardroom to patient?

When a drug is being developed, it has to go through various stages of research called clinical trials or studies. These are intended to establish a safe dosage, what side-effects are possible and for what cancers it may be useful.

They also find out how effective the drug is, and whether it is better than existing treatments. Many promising drugs may be found to be less effective than existing treatments, or to have side-effects that outweigh benefits.

What the side-effects or long-term effects?


Still unknown. Most of those on the trial have not been on it long enough to know.

But so far Gleevac has shown far fewer side-effects than conventional treatments, with mild nausea, skin rashes, muscle cramps, puffiness around the eyesand mild oedema being listed.

The United States cancer institute's Dr Klausner shares the excitement over Gleevac but cautions that some research questions still need to be answered, such as how long Gleevac will control chronic myeloid leukaemia.

What other drugs have shown promise?

At any one time hundreds of cancer drugs are being developed, modified and given trials. A search on the United States National Cancer Institute website for existing trials brought up 1799 listings.

Researchers at the University of New South Wales have invented a cancer drug, glutathionarsenoxide or GSAO, which starves tumours instead of poisoning them.

Another drug which works in a similar manner to Gleevac is herceptin, for advanced breast cancer.

And a new cancer-fighting agent, ZD9331, is in phase two clinical trials after showing great promise in phase one human trials.

What is GSAO?

A biochemist and chemist from the university invented the drug, which works to starve tumours like breast, colon and lung cancers.

It should be equally applicable to any tumour type.

The Sydney Cancer Centre head of clinical research, Dr Michael Millward, is impressed with the drug. He has not been involved in its development.

"It is one the most promising new anti-cancer agents from Australia that I've seen."

It also has potential as an HIV drug. At last report, researchers had hoped to go into phase one of human trials this year. There is no word yet on results.

What is herceptin?

Herceptin has been described as a promising remedy for advanced breast cancer. It targets cells that "overexpress," or make too much of, a protein called HER-2 or erb B2, which is found on the surface of cancer cells. Herceptin stops or slows the growth of these cells.

Herceptin is used only to treat cancers that "overexpress" HER-2, which is about 25 per cent of breast cancers. It can be given by itself, or in conjunction with chemotherapy.

It does have side-effects, including fever, chills, weakness, nausea, vomiting and headaches.

It also can pose possible serious health risks, such as damage to the heart muscle that can lead to heart failure. It can have a detrimental effect on the lungs or cause severe allergic reactions.

It is being tried in America to treat non-metastatic breast cancer also. And it is being studied in clinical trials for other types of cancers, including cancer of the lung, pancreas, colon and ovaries.

Recent research shows that it may modestly extend the lives of terminal breast cancer patients. Scientists say that while the improvement is small - four months on average - it is notable in a disease that has eluded efforts to slow its fatal progression.

And what about ZD9331?

The directors of the Institute of Drug Technology in Australia and a British-based pharmaceutical company, AstraZeneca, signed a contract in May for its development and manufacture.

ZD9331 is being developed for a range of tumours. Encouraging evidence of anti-tumour activity has been seen in melanoma, ovarian, colon and breast cancer.

In trials it has caused side-effects, including vomiting, fatigue and rashes.

It has reached the stage of phase two clinical evaluation internationally.