• Pharmacists urged to play a part in improving epilepsy care
• Fenofibrate reduces progression of atherosclerosis in type 2 diabetes
• Oestrogen replacement therapy doubles risk of ovarian cancer mortality
• Chemoprevention of colorectal cancer gets closer
• New cancer treatment enters trials

Pharmacists urged to play a part in improving epilepsy care

A White Paper intended to improve the lives of people with epilepsy was launched on March 22 at the European Parliament in Brussels, Belgium. Speaking at the launch, Professor Martin Brodie (professor of medicine and clinical pharmacology, University of Glasgow, and chair of the scientific advisory board, European Concerted Action and Research in Epilepsy [Eucare]) said that pharmacists have an important role to play in the implementation of the White Paper by acting as an information resource.

He told The Journal that pharmacists were important when people did not have access to specialist care. These patients could speak to their pharmacist who could obtain the information they needed, he said.

The White Paper was produced by Eucare and is supported by the World Health Organisation, the International League Against Epilepsy and the International Bureau for Epilepsy.

The White Paper has been launched to:

• Improve public understanding of epilepsy and reduce stigmatisation of patients
• Provide legislation to protect people with epilepsy from discrimination
• Increase investment in research into the disease to improve diagnosis and treatment

The White Paper says that “drug treatment should be individually tailored to prevent seizures with minimal side effects”. It also recommends that patients must participate in treatment decisions and that there is a need for new antiepileptic drugs. It explains that epileptogenesis is a process in which changes occur in a group of neurones leading to the formation of an epileptic focus. The underlying mechanisms remain unknown, but new approaches to epileptogenesis “may prove more effective than conventional antiepileptic drugs in preventing the development of post-traumatic epilepsy”, the White Paper says.

Peter Kind (acting director, directorate for health research, European Commission) said that epilepsy was still poorly understood, despite recent advances, and the fact remained that a quarter of patients could not be treated. “Even for those that can be treated, many drugs have devastating side effects,” he said. He thought that a major area of research in the future would stem from knowledge gained from the human genome project because half of all cases of epilepsy had a genetic component. He hoped that this research would lead to earlier identification of the condition and to more effective drugs with fewer side effects, as well as treatment that could be tailored to the individual patient.

Fiona Thomson (senior pharmacist, Institute of Neurological Sciences, South Glasgow university hospitals NHS trust) told The Journal on March 28 that the launch of the White Paper was an excellent opportunity to highlight to primary and secondary care pharmacists the valuable role they could play in meeting the needs of people with epilepsy. “Pharmacists can provide information and advice to people with epilepsy and health care professionals, to help people understand their drug therapy, and identify and resolve pharmaceutical care issues such as appropriate contraception and pregnancy issues, drug interactions, avoiding drugs which may exacerbate epilepsy and ensuring the appropriate choice of drug for co-existing indications (such as depression, or malaria prophylaxis). Community pharmacists may also be able to help ensure patients are referred to specialist services, where available, for appropriate initiation of treatment, by identifying patients commenced on anticonvulsants in primary care.”

Pharmacists were ideally placed to help raise the awareness of the condition and to remove stigma, by general educational and health promotion initiatives, she said. Pharmacist involvement needed to be underpinned by a good knowledge of epilepsy and the issues involved, such as through distance learning packages, she added.

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Fenofibrate reduces progression of atherosclerosis in type 2 diabetes

Fenofibrate, a lipid modulating agent, reduces the progression of coronary artery disease by up to 42 per cent in patients with type 2 diabetes, according to Dr George Steiner (Toronto general hospital, Canada) and colleagues.

Lipoprotein abnormalities are known to increase the risk of heart attacks in patients with type 2 diabetes, they say. Therefore, patients should be tested for abnormal lipid levels when their diabetes is diagnosed, and annually thereafter.

The researchers randomly assigned 418 men and women, aged between 40 and 65 years, with type 2 diabetes to receive either fenofibrate 200mg daily or placebo for at least three years.

The researchers found that, compared with placebo, fenofibrate reduced the progression of minimum blood vessel lumen diameter by 40 per cent. It was also associated with a 42 per cent reduction in the progression of percentage diameter stenosis. These two features can be used to assess localised coronary disease.

The researchers suggest that if any lipoprotein abnormality is identified, even if small, it should be corrected to reduce the risk of coronary disease (Lancet 2001; 357:905).

Michelle Johnson (primary care clinical pharmacist, Primary Care Group Ltd) told The Journal on March 27: “Although patients with type 2 diabetes undoubtedly benefit from intervention with a statin to lower serum cholesterol, it is expected that this study, and other major endpoint studies currently in progress, will lead to the revision of guidance on the management of lipids in diabetes.” However, Mrs Johnson said that, in terms of improved mortality outcomes, further major outcome studies were necessary to determine whether fibrates offered greater benefits over established statin therapy.

She further commented that in most patients with type 2 diabetes, the underlying lipid abnormality was not elevated cholesterol but an altered quality of low density lipoprotein cholesterol. “Fibrates, which raise high density lipoprotein and lower triglycerides, are ideally suited to manage typical diabetic dyslipidaemic profiles. This study proves that the theoretical basis for treating diabetic dyslipidaemia with a fibrate translates into a demonstrable benefit.”

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Oestrogen replacement therapy doubles risk of ovarian cancer mortality

Women who take oestrogen replacement therapy for 10 or more years have a greater risk of developing ovarian cancer, say researchers from the American Cancer Society.

Dr Carmen Rodriguez and colleagues (Atlanta, Georgia) evaluated 14 years of follow-up data for 211,581 volunteers to find out whether there was a relationship between long-term use of oestrogen replacement therapy and ovarian cancer mortality.

They found that use of oestrogen replacement therapy for 10 years or more approximately doubled the risk of ovarian cancer mortality. The relative risk estimate decreased with increasing years since last use. Women who had not used oestrogens for at least 15 years were not at increased risk, but those who had stopped more recently were. Use for less than 10 years was not associated with a significant increase in risk, they say.

The impact of sequential or combined oestrogen and progesterone therapy on ovarian cancer risk is not known (JAMA 2001;285:1460).

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Chemoprevention of colorectal cancer gets closer

Chemoprevention — the use of chemical agents to prevent carcinogenesis — was discussed at a European School of Oncology conference on colorectal cancer in London earlier this month. Dr Bernard Levin (Anderson Cancer Centre, Houston, United States) said: “We don't yet know whether it works or how well it works. But the trials are being done, and in three or four years we should have more evidence.” Dr Levin said that the aim of chemoprevention in colorectal carcinogenesis was to prevent the development of adenomatous polyps and their progression to cancer, with a view to offering therapy to patients at high risk of cancer.

Attention had been focused on non-steroidal anti-inflammatory drugs (NSAIDs) because case control and cohort studies had indicated that long-term use of these drugs was associated with significantly reduced risk of developing colorectal cancer. Colorectal cancer was also reduced in patients with rheumatoid arthritis. The scientific basis for interest in NSAIDs was that the cyclo-oxygenase 2 (COX-2) enzyme was known to be over-expressed in human colon cancer and, in animal studies, inhibition of COX-2 blocked tumour growth.

A study reported last year had found that the selective COX-2 inhibitor celecoxib (400mg twice daily for six months) was associated with a 28 per cent reduction in the number of colorectal polyps in patients with familial adenomatous polyposis (FAP), a rare inherited disease associated with very high risk of colorectal cancer.

But the issue with NSAIDs was not only related to COX-2. “Would that it were so simple,” Dr Levin said. Other eicosanoid pathways might be involved. For example, it was known that a specific lipoxygenase enzyme (15-lipoxygenase -1) was suppressed in colorectal cancer and levels could be increased with NSAIDs. There were other possible molecular targets, and the effect of COX-2 inhibitors on angiogenesis was of great interest. It appeared therefore that the chemopreventive effect of NSAIDs probably involved both COX-dependent and COX-independent mechanisms.

New trials with COX-2 inhibitors were in progress, as were trials with aspirin, sulindac sulfone, calcium salts, folic acid, ursodiol and selenium. Calcium supplements had already been found to have some preventive effect.

Combination therapies might turn out to be most useful, Dr Levin suggested. He emphasised that any chemopreventive agent would have to have proven safety since treatment would be given to patients who were generally well. A variety of dietary substances, including soy isoflavones and lycopene, were also being investigated as potential chemopreventive agents.

Dr Malcolm Dunlop (Medical Research Council human genetics unit, Edinburgh) said that there was increasing understanding of genetic risk factors and gene-environment interactions in the causation of colorectal cancer. “The use of genetics to identify patients at high risk is just around the corner,” he said. Stratification of risk on the basis of a person's genotype would allow specific intervention tailored to the level of risk.

Speaking after the conference, Dr Jack Cuzick (head of epidemiology, Imperial Cancer Research Fund) told The Journal that the initial data on COX-2 inhibitors were certainly promising but large-scale studies were now needed. As an indication of the potential importance of this research, he said that 5 per cent of people aged over 50 had a large adenoma and so might be candidates for chemoprevention.
— Contributed.

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New cancer treatment enters trials

A potential new cancer treatment CV247 that was developed by a veterinary surgeon for treating animals is now being evaluated for efficacy and safety in humans. CV247 has not yet received a patent so its components have not been revealed. However, Ivy Medical, the company developing the treatment, says that it comprises four well-known compounds which, individually, are not known to have anticancer properties.

Speaking at a press briefing on March 27, Dr Robert Thomas (consultant oncologist and lead investigator, Addenbrooke's hospital, Cambridge) said that the philosophy behind cancer treatment with CV247 was to switch off the fundamental pathways of cancer, leaving the cancerous cells dormant. In theory, the components of CV247 acted together to control, rather than kill, cancerous cells, he said. Ivy Medical says that the anticancer mode of action of CV247 is probably related to enhancement and modulation of cyclo-oxygenase 2 inhibition. The company adds that two of the components of CV247 are essential for the production of two antioxidant enzymes (copper superoxide dismutase and manganese superoxide dismutase), which reduce the oxidative stress that has been implicated in carcinogenesis and malignant progression.

All patients entered into the trial have progressive disease (prostate, colorectal, ovarian and miscellaneous cancers) that has not been treated successfully with existing therapies. The first results on the efficacy and safety of CV247 in humans are expected later this year.

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