How much is a life worth? How much are 10 or maybe 20 months of life worth? The moral calculation that lay behind last week's decision to make the breast cancer drug Herceptin available on the NHS is not one that any of us would care to perform. In the case of Herceptin, the National Institute for Clinical Excellence (Nice) decided that spending about £17m a year to give 2,000 women an extra 10 months or so of life was worth it. But suppose it had been £30m and only 1,000 women?
Such impossible yet essential calculations are going to become more and more common as a direct result of the type of drugs coming out of the research labs. Herceptin, launched about three years ago, is actually rather old hat. It was a forerunner of a new generation of drugs that exclusively target cancer cells, which have been generating great excitement in recent months.
The promise is that they will both be more effective and produce fewer side-effects than the carpet bombing of chemotherapy. A drug called Glivec, for instance, was reported to have halted the progress of two rare and hard-to-cure forms of leukaemia in 90% of patients last summer. A trial of another, known as Erbitux, achieved dramatic success in treating severe colon cancer. Both drugs will be fearsomely expensive.
The assumption behind the new targeted approach is that cancer is really several hundred separate diseases, each caused by a different combination of faulty proteins and enzymes produced by the mutated genes. The hope is that by using some of the newly discovered tumour markers, doctors will be able to detect cancer much earlier, define what kind it is and then treat it specifically.
Dr John Mendelsohn, president of the MD Anderson cancer centre in Houston, Texas, and the researcher who developed Erbitux, describes how it might work. "The dream is that if Mrs Smith gets a breast biopsy, we'll be able to say, 'Here are the four genes that are abnormal in your tumour', pull open a drawer, pick out the drugs designed against the abnormal products of those genes and give her a cocktail targeting the genes that caused her cancer."
To the limited extent that this dream is now a reality, Herceptin targets an "abnormal product", a growth factor known as HER2 found in breast cancer. Erbitux and Glivec generated such excitement because they target a close cousin of HER2, which is much more widespread, being found in 50% of cancer types. They block EGF (epidermal growth factor), which is found in all the cells that line our organs and in skin. Cancer patients with high levels of EGF don't do well.
It all sounds impressively precise and scientific, but before breathing a sigh of relief, it is worth remembering just how often we have been here before. In December 1971 President Nixon made funds available for a war on cancer and set 1976 as the victory date. It was wildly premature. In the US today more than a million people are diagnosed with cancer every year and 50,000 die.
A devastating analysis of the campaign and its false dawns was published last year in the New Yorker. Among the magic bullets regularly promised in the 70s and 80s were the immune boosters such as interferon and interluken-2, which turned out to be largely duds. "Hundreds of thousand of cancer patients underwent experimental treatments; in most cases the pain and discomfort caused by the side-effects were unaccompanied by any genuine benefit," concluded the author Jerome Groopman, chief of experimental medicine at Boston's Beth Israel Deaconess medical centre.
As a measure of the failure, Groopman quotes a controversial statistical analysis published in the New England Journal of Medicine, which found that, despite research budget of more than $8bn, there had actually been a 6% increase in cancer mortality between 1970 and 1994. The quarter of a percent dip that has showed up more recently was attributed to reduced cigarette smoking and improved screening, rather than to any breakthroughs in treatment.
So a degree of scepticism over the latest claims of a breakthrough seems in order and the truth is that the new generation of drugs are not working quite as well as the PR suggests. As a report in the New Scientist in December showed, resistance to Glivec can develop rapidly if it isn't given early enough, because rapidly dividing cells in a tumour is just the place to throw up a range of mutations that allow the tumour cells to become resistant. In the initial Erbitux trial, out of 125 seriously ill patients, only 27 of them saw their tumour shrink by more than 50% - a 22.5% response rate. That is double the normal rate for such sick patients, but still nowhere near a cure.
Given that these new sniper-rifle style treatments were supposed to replace the old blunderbuss approach of chemotherapy and radiotherapy, it's ironic that where they do seem to be scoring is in combination. In one study, the survival rates after a year for pancreatic cancer patients given Erbitux plus chemotherapy was 32.5% - double that of Erbitux on its own.
The real significance of these new drugs is not that they promise a cure, but that they may herald a new way of treating cancer. "Some day we may treat cancer as a chronic manageable disease, very much like we treat heart disease now," says Dr Judah Folkman, of Children's Hospital in Boston. The idea is that cancers only become deadly when they spread, so you keep them corralled with the new drugs and occasionally blast them with chemotherapy.
This is why the impossible moral calculation that Nice had to perform over Herceptin is going to become far more common, because the new approach will result in a massive increase in drug use. Instead of a relatively brief course of chemotherapy, the idea is to get cancer patients on to a cocktail of the new targeted drugs, which they may have to take for years. The current cost of chemotherapy is around £3,500 to £4,200 a year. Compare that with the monthly cost of £1,600 for Glivec, and some of the other new drugs are even more expensive.
But what is the alternative? Prevention is always the sensible option - US figures suggest that 500,000 cases of cancer might be prevented by changes in diet, physical activity and lifestyle, while an improvement in detection rates could increase survival rate after five years for accessible cancers, such as those of the breast, colon and cervix, from 61% to 95%.
But, of course, when it is your cancer and it's now, you want something, anything. So the question that is going to be asked with increasing frequency is: "Who's going to pay?"
· A longer version of this article appeared in the February issue of the newsletter Medicine Today. www.medicine-today.co.uk
