Lower doses enable older bowel cancer patients to take part in chemotherapy trials

In collaboration with Adfero

Older patients with advanced bowel (colorectal) cancer may be able to take part in clinical trials if the doses of experimental chemotherapy drugs are lowered to reduce the risk of harmful side effects, according to research part-funded by Cancer Research UK.

Bowel cancer is more common in older people, with 60 per cent of deaths from the disease occurring in patients over the age of 75.

However, elderly patients are under-represented in clinical trials for new bowel cancer therapies. The average age of trial participants is currently ten years lower than that of bowel cancer patients in the general population.

This is thought to be largely due to patients' increasing frailty as they get older and doctors' reluctance to expose them to the potentially harmful side effects of full-dose chemotherapy.

Now, scientists in the National Cancer Research Institute (NCRI) Colorectal Clinical Studies Group have shown that by reducing the doses of chemotherapy drugs, it is possible for older patients to take part in trials.

This is important, as it means doctors will have solid evidence about the benefits of treatment in this group of patients in the future, rather than having to estimate their effectiveness based on outcomes in younger, fitter patients.

The research team - who also received support from the Medical Research Council and the National Cancer Research Network - organised a large-scale, randomised trial testing different combinations of chemotherapy in more than 450 bowel cancer patients at 61 NHS hospitals across the UK.

Patients were 74 years old on average, and a quarter were over 78 years of age - meaning that many would not have participated in an ordinary clinical trial.

The researchers measured various aspects of each patient's fitness before calculating a reduced dose of chemotherapy designed to limit the chances of harmful side effects.

Patients were randomly chosen to receive either rceived injections of a drug called fluorouracil or tablets of capecitabine, combined either with or without another drug called oxaliplatin.

All patients started on 80 per cent of the standard doses of each treatment, but this was increased after six weeks if the side effects were manageable.

Publishing their findings in the Lancet medical journal, the study authors revealed that the results had been encouraging, with more than half of the patients reporting improvement in their quality of life during the 3 months after starting chemotherapy.

Oxaliplatin produced less benefit in this group of patients than in younger, fitter patients. However, it still provided significant improvements in the 'overall treatment utility' - a method of assessing cancer therapy that combines cancer shrinkage, survival time and a patient's own assessment of the therapy's worth and impact on quality of life.

The study authors concluded: "FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial.

"We encourage investigators to continue to design trials using appropriate low-toxicity treatments and patient-centred assessment to expand the evidence base in this important specialty."

Matt Seymour, Cancer Research UK's professor of gastrointestinal cancer medicine based at the University of Leeds, and study leader, said: "Bowel cancer, like many other types of cancer, often occurs in elderly people who may be frail or have other health problems that can make treatment more challenging. But most trials of cancer treatments involve younger, fitter patients. Doctors are then faced with the dilemma of how best to use those trial results to treat patients who are older and less fit than those in the trial.

"So we set up a large national trial to investigate how clinical trials could be better designed for older and frailer patients. The results were very encouraging - lowering the starting dose of chemotherapy reduced side effects and, by carrying out a health check before treatment, we were able to develop new ways of predicting whether patients were more - or less - likely to benefit from chemotherapy.

"These results should go some way towards ensuring that more elderly patients are offered the chance to take part in research in the future," he added.