Life on trial; UNDER THE MICROSCOPE

My interest in cancer has become very personal as my wife recently died from malignant melanoma. When she was diagnosed there was nothing realistic that could be done although they offered faint hope and excellent palliative care. So all the more relevant is a recent article in the authoritative New England Journal of Medicine entitled "Cancer Undefeated".

The authors' analysis claims that, when adjusted for age, the deaths due to cancer increased by 6 per cent from 1970 to 1994. However, there had been a reduction in mortality in those under 55 and this most likely reflects reduced cigarette smoking and earlier diagnosis. While there has been very significant progress in a few cancers such as childhood leukaemia, testicular cancer, and some lymphomas, treatment of many of the major cancers like lung and malignant melanoma has so far not shown much improvement. For these reasons the authors suggest a substantial shift of effort from basic research that could lead to treatment, to prevention.

But this seems to be an unnecessarily negative view for molecular biology has provided excellent advances in understanding what goes wrong in cancer cells. The difficulty is in applying this know-ledge to treating cancer patients. What is needed are treatments that kill cancer cells but leave normal cells intact. The problem is that the differences between a cancer cell and a normal cell can be subtle involving alterations in just a few genes, sufficient to cause uncontrolled growth and spread. The absence of normal controls makes cancer a chaotic system so very small local changes can have dramatic effects; for example, a blood vessel approaching a group of dormant cancer cells can lead to their explosive growth with disastrous results.

In order to find out if a treatment for cancer works it is absolutely essential to do clinical trials. This requires that patients be assigned randomly to one of the two treatment regimes being compared. But, the ethicists ask, is it really alright to use patients effectively as guinea pigs? Do clinical trials remove patient autonomy and remove their rights? Quite the contrary, for there is a strong moral imperative for all cancer patients to be in clinical trials as they can contribute to the future good of other cancer patients. Moreover, their own treatment is dependent on those who entered earlier clinical trials. By blocking clinical trials bioethicists are, in fact, causing the unnecessary death of patients by delaying knowledge of the best treatment from being obtained.

For the country as a whole less than 10 per cent of cancer patients are in a clinical trial. The reasons for this disappointingly low figure are various. For a patient to enter into a clinical trial there has to be informed consent. The doctor has to explain exactly what the trial involves and that the patient will be randomly assigned to a particular treatment. Some patients are resistant to what they may perceive as a lottery approach, or do not wish to be used as part of an experiment, little realising that many medical treatments, unlike well-planned trials, are uncontrolled experiments. Trials are only carried out when there is insufficient evidence to make a safe choice of the appropriate treatment.

Another reason for the small numbers of clinical trials is that the explanations required to obtain informed consent take time, sometimes up to an hour. This has to be contrasted with the 15 minutes usually allotted to a clinical consultation. Also, the number of cancer doctors is less than half that needed and so the pressure on time in dealing with new patients is very severe. Why there are so few cancer doctors is historical and partly reflects that it is a relatively new discipline which has not acquired medical muscle. They may have colluded with shortages too easily by working too hard.

But what is becoming clear is that patients have duties as well as rights - one of those duties is to enter well-designed trials.