In recent years, the field of oncology has changed quite dramatically because of the availability of new agents which are more effective against certain types of cancer. These newer agents include: (1) trastuzumab (Herceptin) and the aromatase inhibitors anastrozole (Arimidex), exemestane (Aromasin) and letrozole (Femara) for breast cancer; (2) bevacizumab (Avastin) and cetuximab (Erbitux) for colorectal cancer; (3) erlotinib (Tarceva) and pemetrexed (Alimta) for lung cancer; (4) rituximab (MabThera) for non-Hodgkin’s lymphoma, and (5) imatinib (Gleevec / Glivec) for chronic myeloid leukemia.

A report from the Karolinska Institute and the Stockholm School of Economics looked at access to new anti-cancer drugs in United States, Japan, Canada, Australia, New Zealand, South Africa and 19 European countries. These 25 countries accounted for 984 million people only. The study has found that access to new anti-cancer drugs varies widely in these 25 countries. Uptake of new anti-cancer drugs is highest in the United States, Austria, France and Switzerland but it is ‘low and slow’ in the United Kingdom, New Zealand, South Africa, Poland and the Czech Republic. For example, the uptake of bevacizumab in the United States is 10 times the European average (E13, representing average sales in Austria, Belgium, Denmark, Finland, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland and the United Kingdom). Italy and the United Kingdom have a very low uptake of bevacizumab. From this it would be clear for all to see that the availability of some new drugs differs in the countries you reside in. This in turn can have an adverse impact on patient prognosis. In the past 11 years, close to half of the oncology drugs coming to the market were launched in the United States. This is due to the fact that consumers there can afford to pay for these expensive new drugs as compared to the consumers in some European countries.

Indeed, the National Institute for Health and Clinical Excellence (NICE), Britain’s medical cost-effectiveness watchdog, has recommended against using erbitux in colorectal cancer in the National Health Service. In contrast, erbitux is used relatively freely in the United States. More recently, NICE has also ruled against the use of erbitux in combination with radiotherapy for patients with head and neck cancer (Reuters, 14th May 2007). The Chief Executive Officer of NICE stated that “The NHS has finite resources and it is our job to ensure that these are spent on treatments that confer enough of a benefit to patients in relation to the amount of money they cost”.

From the patient’s perspective, cost should not be the issue in deciding whether a new drug is made available to him or her or not. That may be true in a social health care system with unlimited resources or in a private health care system where patients have ample coverage. However, the reality of the matter still boils down to dollars and cents. For example, in Singapore, a first world country, erbitux is not freely available in the national health system. If you want it, you have to pay for it. The cost of a single dose of erbitux is around S$10,000 in the private sector. As palliative chemotherapy is to all intent and purposes indefinite, not many would be able to afford the hefty medicine cost for a prolonged period.

Will cancer medicine cost go down the same route as HIV medicine cost? Will it reach a point where less well off countries and societies demand that these new anti-cancer drugs be made available at much lower cost? Judging from the fact that there are more people affected by cancer than AIDS worldwide, I would not bet against it.

The lifetime risk for developing colorectal cancer in the developed countries is estimated to be 5%. Every year there are about 1 million new cases of colorectal cancer worldwide and it is the second most common cancer in developed countries. It is now widely accepted that colorectal cancer develops from initially benign colorectal adenomas (polyps) in the colon. In developed countries 40% of the population will have one or more polyps by the age of 60. However, fewer than 10% of these adenomatous polyps will progress to cancer. Several randomized trials have shown that aspirin and cyclo-oxygenase 2 enzyme (COX-2) inhibitors reduce the recurrence of adenomas by about 40% in patients with previous adenomas or colorectal cancer. While we know that adenoma recurrence can be reduced by using medications that inhibit COX-2, their potential usage to prevent the development of colorectal cancer is still inconclusive. (It is not advisable to take COX-2 inhibitors long term because of  known adverse vascular risks. For example, Pfizer, the manufacturer of Celebrex, a COX-2 inhibitor, is facing law-suits from patients who have suffered side-effects from taking the medicine.) It is however feasible to take aspirin on a long-term basis. What is the evidence to support its role in preventing colorectal cancer? Indeed some studies have shown that long term usage of aspirin did not impact on the occurrence of colorectal cancer in the first 10 years of follow up. So is our hypothesis wrong? Perhaps not.

Researchers from Oxford recently reported (Lancet 2007; 369: 1603 – 1613) the results from two large randomized trials set up to study the effect of aspirin – the British Doctors Aspirin Trial (N=5139, two thirds allocated 500 mg aspirin for 5 years, one third to open control) and the UK-TIA Aspirin Trial (N=2449, two thirds allocated 300 or 1200 mg aspirin for 1 – 7 years, one third placebo control). In the first 9 years of follow up, there was no effect seen on the incidence of colorectal cancer. However, by 10 -19 years of treatment, there was a significant difference in the incidence of colorectal cancer seen in those who were taking aspirin. In the UK-TIA Aspirin Trial, the number of colorectal cancers expected to develop in the group of patients taking aspirin was 30. The actual number of colorectal cancers found was only 15! Similarly in the British Doctors Aspirin Trial, the expected number was 72 cases of colorectal cancer but the actual number of cases was only 50! These researchers also found that long-term ingestion of aspirin had no preventive effect on other solid cancers, such as those arising from the oesophagus, stomach, pancreas, kidney, lung, prostate and breast.

This report has highlighted several points in medical research / studies. Firstly, the initial aim of the two studies was not to look at whether aspirin could prevent colorectal cancer or not. However, as the relevant data was captured in the course of the study and the data captured was complete and accurate, it allowed the researchers to answer other significant health questions. Secondly, it highlights the fact that in matters of health and diseases, 10 years is a relatively short time. The beneficial or detrimental effects of a particular medicine or treatment may not be obvious until you have a long enough follow up period.

These Oxford researchers are not advocating that everyone should be taking a minimum of 300 mg of aspirin per day in order to reduce the incidence of colorectal cancer. So, before you rush out to buy your supply of aspirin, please pay your own doctor a visit and discuss it with him first. Remember, aspirin has its side-effects too.

An odd statement you would have thought. The statement refers to when to call it quits with any form of treatment for patients with an incurable condition. This statement is more often asked or encountered with cancer patients but it is also very relevant to patients with progressive neurological conditions and chronic lung diseases to name a few.

A recent study on the effect of aggressive treatment on quality of death in cancer patients was presented at the American Geriatrics Society (AGS) annual meeting in Seattle, USA. The researchers from Carnegie Mellon University interviewed 243 advanced cancer patients and their caregivers. (Aggressive treatments included intensive-care-unit stay, ventilator support, resuscitation, use of feeding tube, non-palliative chemotherapy and antibiotics.) The study found a correlation between the number of aggressive treatments received in the last week of life and increased psychological and physical distress. Consequently, the quality of death was considered to be lower for those who had had aggressive treatment. Approximately 90% of patients who received no aggressive treatments in the days preceding their death died in their preferred location. In those patients who received 2 or more treatments, only one third of them died in their preferred location. Those patients who received longer duration of hospice care had significantly less physical distress, higher quality of death and a greater probability of dying in their preferred location. Patients who received at least 5 weeks of hospice care were in less physical distress in their last week of life than those who had < 1 week of hospice care (AGS Annual Scientific Meeting 2007; Abstract P4).

Irrespective of causes, for all patients with limited life span, quality of life is paramount. Recently, a patient of mine, in his late 50s, with disseminated colorectal cancer came to see me after visiting his oncologist. While the newest targeted molecular drug appears to have held his disease at bay, the side effects were significant and he requested a change of medication. This change however was not effective in containing the disease. He was troubled by the prospect of no more treatment except with experimental drugs and the fear of drug-related side-effects. After a long discussion, he came to the conclusion that he probably wanted a break from further treatment to ‘allow his body to recover’ but wanted to know what I thought. I did not hesitate in concurring with him that, in his case, it was an appropriate decision.

Taking a break from chemotherapy, in a palliative setting, is not wrong. The reasons for the break can be medically indicated or personal. The goal for these patients is an attempt to prolong life. For most if not all patients it is hoped that the prolongation is achieved with preservation of a good quality of life. For a few, the quest for this prolongation is sadly to be done at all cost. Patients who request ‘all out’ treatment may do so out of distress and hoping that any form of treatment will reduce the distress experienced.

In these situations, the doctor’s role is to guide them in making the right choice. A choice that is most suitable for the patient himself / herself. With time, compassion and a sympathetic ear, it is possible to tailor a management plan that suits the patient. To paraphrase William Osler, a good doctor treats the disease while an excellent doctor treats the person with the disease.