KEY POINTS:
For Dr Michelle Vaughan the Phase two DMXAA ovarian cancer trial was excellent news. She already knew about the new, locally developed drug DMXAA. As one of Auckland Hospital's 11 medical oncologists (cancer specialists), and only three who specialise in gynaecological oncology, 41-year-old Vaughan had worked before with its developer, Professor Bruce Baguley, who was based across the road at the Auckland Cancer Society Research Centre in the Medical School.
She knew the role of the Cancer Society in the early funding of the drug. More importantly, after a conference in Istanbul, she was aware of its early promise.
So she was delighted when her patient, Wendy Cook, was accepted on the trial. As she explains, women who present with ovarian cancer are nearly always at stage three or four when they arrive. By that time their cancer has metastasised, spread to their lymph nodes which transport rogue cancer cells to other parts of their bodies. "We can offer them a lot - surgery, radiotherapy, chemotherapy - but not a great deal of time."
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On randomised trials like this, an electronic programme flips the dice and decides which half of the patients gets the new drug and those who don't.
The DMXAA trial involved patients with relapsed ovarian cancer. Auckland had only two slots - and in the fall of the electronic dice, Wendy was the lucky one. For her, the new drug was a lifeline. By the time she was accepted on to the trial in October last year, her cancer had come back for the second time. Her disease was stage four. The Auckland City Hospital clinical services planner is not under any illusions about cancer cures, but she told her oncologist, smiling but serious: "I accept your diagnosis, but I reject your prognosis".
She was willing to try the new treatment. "The thing is, you may get an extended period [of life]. I was also thinking about what it may do for some other women further down the track," she says. She also realised that even if the DMXAA did not work, she would get another dose of the expensive and highly effective chemotherapy drug, paclitaxel, which was only funded for one treatment - and she had already had hers.
She read the information provided by the scientists, thought about it overnight and made her decision. "What have you got to lose?"
With conventional chemotherapy, successive scans show tumours slowly shrinking away. With the addition of DMXAA Vaughan noted that Wendy Cook's tumours appeared to die from the inside out.
"Wendy's case was particularly interesting. I saw something happening in the lesions - the little lumps of cancer inside the abdomen. In her case, the tumour went black in the middle, then disappeared, which is something we don't usually see."
Again, Cook turned out to be one of the lucky ones. Her response to the combination of conventional ovarian cancer chemotherapy chased down with 2000mg of DMXAA was dramatic. By January 17 this year, a week before her last icy treatment, the CT scan showed no lesions whatsoever.
Cook's challenge started in the winter of 2002. She was 52, fit and independent with a substantial career that included nursing in Thailand, then moving into health management in Geneva, China, the Philippines, Papua New Guinea, then back to Auckland.
Now her cough would not go away. "I was back and forth to my GP. She couldn't work out what was wrong and sent me for a gastroscopy. That found nothing, so my GP suggested a second opinion."
When the popular woman with the lightbulb smile and upbeat personality couldn't keep up with her friends and had to call for them to "slow down", she knew she was in trouble. Her GP talked to a colleague at Green Lane.
The chest x-ray showed her right lobe was full of fluid. "They drained it that day, tested the fluid and the next day the respiratory consultant told me I had a cancer, but not of the lung."
She had ovarian cancer that had invaded her lung and abdomen cavity.
Vaughan gave her the "unacceptable" prognosis: "You have stage four ovarian cancer which is incurable. Hopefully we can induce a remission that will last months, possibly years."
First came the operation to remove the tumour, followed by six doses of chemotherapy - and three years of normal life. "Wendy's a legend around here," says Vaughan. "She sat in the chemo room with a drip in one arm and a whole pile of papers she was working on in front of her."
Cook also went across to the Cancer Society's Look Good, Feel Good session at Domain House, for a massage, advice on wigs - and the free makeup they were offering.
Armed with the lot, she felt great. "I went back to work and continued to do really well."
But just before Easter last year, Cook developed a nasty ear infection. Soon the dizziness was so severe her doctor insisted she call 111 and get into hospital fast. Although she "didn't have a clue that this was anything more than a particularly bad middle-ear infection", an MRI scan showed her distress was caused by a walnut-sized brain tumour caused by a rogue ovarian secondary cancer cell.
This time Cook was shattered. "At first I thought it was the beginning of the end," she says. "But then you just keep on going - you have to. And my philosophy didn't change: 'I accept your diagnosis but I reject your prognosis'."
Treatment was harder. She was advised to take three months off work. Steroids got her in shape for another huge operation, a CT scan showed more secondary tumours in her belly, and she had 23 doses of radiotherapy to blast the brain tumour. And this time, a potential extra weapon, the DMXAA-laced chemotherapy.
The DMXAA results on lung cancer had shown big promise. Auckland oncologist Mark McKeage, who returned last weekend after presenting his DMXAA trial results to a 2000-strong international conference of cancer experts in Prague, says treatments targeting the blood vessels in tumours are the new hot topic in international cancer research. "It's very exciting data, it's remarkable really so it's generating a lot of interest."
At 48, McKeage, who graduated from Otago Medical School in 1982, has a right to be excited. He worked with Bruce Baguley and Bill Denny as a research fellow when writing his masters thesis about DMXAA and related analogues.
"It's been a long project. A few of us have been involved since the beginning and it's been very exciting. It could change the treatment for lung cancer [and potentially all solid tumour cancers] worldwide."
These difficult-to-treat solid tumours are the most common tumours and often the most lethal. "For example, lung cancer accounts for 10 per cent of all deaths."
McKeage points out, in the field of cancer chemotherapy there are occasional, rare breakthroughs associated with a massive improvement in cancer cure rate or survival, but most advances happen incrementally. "A decade ago this form of lung cancer was untreatable. Half the patients died within five months and only 15 per cent were alive at one year."
The latest results show that, with standard treatment, survival was 8.8 months and with DMXAA administered with the best-of-the-rest chemotherapies, 14 months.
The Phase three trial will survey 1000 people, 500 with the drug and 500 without, selected from across the world. Although Auckland medical oncologists are likely to manage some trials and Baguley and Denny will be involved in an advisory capacity, the British biotech company, Antisoma, will be in charge.
While the third trial, on prostate cancer, is not finished, preliminary data is similarly promising. With prostate cancer, the effectiveness of the drug is measured by the presence of prostate-specific antigen (PSA). Early results show the proportion of men showing disease progression by PSA was almost halved in the DMXAA group. Says Baguley, with an unusually wide smile, "It worked on three out of three!"
For Dr Michelle Vaughan, smart and fast-talking like every mother who needs to be home after school, the DMXAA trial meant a pile of extra work. Vaughan, the first female medical oncologist at Auckland Hospital, is highly regarded for her way with patients and her clinical excellence. Her husband, Justin, a doctor and former New Zealand test cricketer, is behind BrainZ, a bedside monitor that tests brain injuries in newborn babies. From either his doctor's or businessman's perspective, he understands his wife's tremendous workload.
First, all prospective DMXAA trialists had to be screened for suitability. Those on antidepressants (common with incurable cancers) and anti-allergy medication (often prescribed to counteract the side effects of chemotherapy) cannot tolerate DMXAA. Those who are suitable need extra, careful monitoring.
The DMXAA was administered after the standard, high performance carboplatin and paclitaxel chemotherapy, in a separate dose calculated by the skin surface of each patient.
Wendy Cook had an unusual response. For the full 20 minutes the drug dripped into her arm, it felt like ice. Even she needed a support person. An hour later, however, she was back to normal with no sign of the heart arrhythmia and visual disturbances Vaughan was looking for.
Treatment continued for five cycles, when Cook's platelet count fell too low to tolerate more. Her progress was monitored with laboratory and clinical examinations backed by six-weekly CT scans. "From the beginning we could see that something unusual was happening."
The final scan, in January this year, showed a minor miracle. The tumours that showed up three months before, attached like small sea anemones to the inner lining of her belly, had disappeared.
For all the hype, all the attention, all the excitement, Vaughan retains her "clinical equipoise - that in our own minds we think no trial is any better or will work better" and keep DMXAA in perspective.
"Wendy is very much aware, and we both know, that it will recur. This is another agent that will add another increment, but experience tells us that all these things are just increments - will only extend the time before the cancer comes back."
She is not brutal but she doesn't deal in false hope either. "The time gained is usually in the order of months."
On the other hand, says Vaughan, "getting something to Stage three trial is as good as it gets.
"Normally by the time a drug gets to Phase three there's a greater than 50 per cent chance it would be a commercial success. It is an enormous credit to Bruce and the team. And it's nice to tell patients that we have something home-grown - that we have expertise on tap."
Nine months later they heard the good news: the response rate for people like Wendy Cook receiving standard chemotherapy plus DMXAA is 75 per cent. With chemo alone it would have been 63 per cent.
Says Cook, "I saw Michelle [Vaughan] last week. She's very pleased. It's a great Christmas present." And, in an aside, "Pharmac were $19.7 million under budget last year ... "
Yellow stuff made me chunder but saved me
When Blair Wingfield arrived at Auckland Hospital in October 1981, covered in yellow bruises and cuts that wouldn't heal and with his lips bleeding after eating French bread, the doctors who diagnosed acute myeloid leukemia gave him days to live. "They said I wouldn't see 40."
Twenty-five years later he attributes his energetic, disease-free life to Professor Bruce Baguley's then-new chemotherapy, Amsacrine - "that yellow stuff that made me chunder for three days" - and stress management. "Attitude is huge to survival," says Wingfield. "When all of medicine meets faith, a miracle happens - it's called hope."
He set goals: getting through that first, terrible night, then the next day; making it to the end of the week; his son's eighth birthday; getting out of hospital for his 40th on Guy Fawke's Day; Christmas, New Year, then going back to work in March 1982.
"I drew down on myself for those first three weeks," says the super-energetic insurance broker. "It was like being in a pyramid. I drew all my energy together and some inner voice said, 'We've got to get through this'."
Within a month he was in remission, 18 months later, after 15 doses of Baguley's "amazing" yellow medicine, the doctors considered him cured.
The Medical School asked him in as an example of what could be done with the new chemo. "And the first question the students asked me, both times, was 'were you under stress at the time?' "
It had been the most stressful period of his life: four years of broken sleep with babies; the death of both parents within a year of each other; a huge workload, and his 40th birthday was looming.
But he puts his survival down to stress management and staying positive. "You've got to get rid of negative people. They just drain you."
Although he doesn't follow a formal anti-cancer diet, he has dropped 20kg over the past two years. He doesn't drink coffee or eat dairy products - "and I haven't had a [alcoholic] drink in two years".
The dos, don'ts and maybes of guarding against cancer
Expert opinions vary on most aspects of cancer and diet - and what you can do to keep yourself cancer free - but one fact stands out: the data on smoking is conclusive. Cigarette smoking accounts for 80 to 90 per cent of lung cancers.
But rigorous scientific evidence that shows that diet can prevent, or cure, cancer, is still elusive.
Associate Professor Brian Cox of Otago University says, "Cancer's not like a cough or a cold. Often it takes at least a decade to get symptoms. If someone gives up smoking he or she can develop lung cancer 15 years later.
"For asbestos cancer the average time between exposure and symptoms is 40 years. Cervical cancer takes 25 years on average to develop after exposure to the papilloma virus."
All of which makes the hard evidence on foods as either preventive or harmful, a long time coming.
Auckland University's Professor Lynnette Ferguson, who specialises in diet and cancer, is convinced 30 to 35 per cent of cancer is diet-related.
"There's a clear message coming out from the various research projects," she says, referring primarily to two of the most important.
The Epic project (European Prospective Investigation into Cancer and Nutrition) is studying the role of diet and lifestyle in cancer development, by studying half a million people in 10 European countries. The project started in 1992 and is intended to continue for the next decade at least.
The second is The World Cancer Research Fund in which researchers undertake over 30 projects annually. Their verdict: "Eating healthily, plus staying physically active and maintaining a healthy weight can cut cancer rates by 40 per cent."
"There's so much you can do to help yourself," says Ferguson. "Those 10 per cent of cancers related to viruses are harder to affect so beneficial vaccines are also important."
Ferguson recommends a mixed diet, possibly colour-coded.
"It's very wrong to see one food as a super food. Mix things up. Eat a wide range of foods. And remember, even broccoli, which seems to protect against a range of cancers, can be toxic in large amounts."
What works (Based on convincing evidence.)
* A high fibre diet reduces colorectal cancer risk (Epic Study).
* Refrigeration of food protects against stomach cancer.
* Physical activity protects against colon cancer.
What probably works (Based on "convincing evidence of causal relationships with the risk of cancer, or else from evidence of probably causal relationships", World Cancer Research Fund).
* Lots of vegetables or fruits protect against cancers of the mouth, pharnyx, oesophagus, lung, stomach, colon, rectum, larynx, pancreas, breast, bladder.
What almost-probably works (Evidence still coming in)
* Omega three fatty acids (fatty fish)
* A glass or two of red wine daily
* Cooked tomatoes (some evidence of protection against prostate cancer)
* Selenium. A New Zealand study, which is part-way through, is showing encouraging early results on the role selenium plays in protecting against prostate cancer. Men interested in taking part in the study should contact Professor Ferguson at the University of Auckland. l.ferguson@auckland.ac.nz
* Blueberries
* Oats
* Spinach
* Garlic
* Nuts
* Green tea, oleic acid from olive oil and apigenin from parsley, thyme and peppermint (these can significantly protect against some types of breast cancer).
What causes cancer (Based on convincing evidence)
* Alcohol increases the risk of cancers of the mouth, pharnyx, larynx, oesophagus and liver.
* High body mass (being overweight) increases the risk of cancer of the endometrium.
What may predispose to cancer
* Too much salt (limit this to under 6g a day)
* Too much red meat (limit to 85g three times a week)
* Over-cooked, especially char-barbecued meat, fish or chicken, eaten more than twice a week
* Stale nuts and grains (buy fresh, store in freezer)
Vaccinations
* Human papilloma vaccine may reduce the risk of cervical cancer.
* Hepatitis B vaccine may reduce the risk of developing liver cancer in the future.
What doesn't work
* Synthetic vitamin C
