A research nurse processing trial samples

In the third and final part of our series on old age and cancer, we look at how research could help to adapt and improve treatment for older patients.

Cancer is often described as a disease of ageing. And a key part of understanding any disease is studying its causes.

This means that finding better ways to treat and care for older cancer patients must include research that includes them.

We’ve blogged already about how the number of older people diagnosed with cancer in the UK is expected to grow rapidly in the next 20 years. And with this comes a growing need for the NHS to support these patients and give them the best possible treatment and care.

By better understanding age itself, and through inclusive clinical trials, research can help make this happen.

Understanding age

Our bodies change a lot as we age, from how our immune system functions to how we process drugs. All of which needs to be considered when planning cancer treatment.

“There’s some early evidence to suggest that how we clear some drugs from our system slows down as we get older,” says Professor Matt Seymour, a Cancer Research UK-funded clinical trials expert.

This could mean that if the same dose of a drug were given to a 25-year-old and a 75-year-old, the 75-year-old may end up being exposed to the active part of the drug for longer, because it stayed in their system. This could increase their risk of side effects.

“It might be that we need to adjust the dose of the drug, to make sure we’re keeping in a safe range,” says Seymour. “We also need a much better understanding of the impact age has on the processing of drugs in the body.”

Older patients are also more likely to have other medical conditions, which may require treatment. And some of these medications could interact with cancer treatment, causing unexpected side effects. These interactions need to be accounted for too.

Right now, a lot of this evidence is missing. When cancer drugs are developed, scientists run rigorous experiments to measure how the drugs interact with the body. But according to Seymour, older patients are often missing from these studies.

Another area that’s raising questions is immunotherapy. Immunotherapy drugs alter how the immune system works, making it better at fighting cancer. But as our immune system changes as we age, questions remain about how these drugs work in older patients.

“There’s some evidence that immunotherapy drugs are just as effective in 65-75-year-olds but may be less effective in the over 75s,” says Dr Alastair Greystoke, a Cancer Research UK-funded expert in cancer and the elderly. “But why this could happens is less clear. Is it because the immune system is less effective, frailty or other diseases the patients have? These are the questions we need to start addressing.”

Beyond a number

When it comes to cancer treatment, age needs to be considered. But it’s not a simple case of looking at the numbers.

“There are older people who are very frail and there are others who aren’t frail at all, even though they’re the same age,” says Seymour. “It’s not all about looking at age, it’s more about how age has affected everything else.”

Researchers are investigating different ways to measure how well someone might cope with treatment.

One approach is to use a panel of tests that aims to objectively measure someone’s fitness levels as well as their support needs, called a geriatric assessment. But researchers are also looking at certain markers in the blood that could help gauge a person’s level of frailty.

Greystoke is trying to develop a blood test to quickly and accurately assess which patients would benefit from a treatment, and who might be at risk.

The test looks at several markers in the blood that identify how the immune system and metabolism are working, among other things.

“The test could help us work out what their treatment options are, and how likely they are to tolerate and respond to treatment without it impacting their quality of life,” says Greystoke.

Scientists are also combining geriatric assessments and blood test in clinical trials, to work out the right dose of chemotherapy for each patient.

“We’ve run a number of trials involving older patients where we’ve assessed people’s fitness before assigning them to receive different levels of chemotherapy. And then we tried to identify factors that can help us predict whether someone was going to do well on chemotherapy, and what dose might be best,” says Seymour.

“The aim is to personalise treatments for patients who are older and less fit.”

Getting patients ready for treatment

If scientists can design tests to understand who might be at higher risk from treatment, doctors can do something about it. Having the data is key.

“People are starting to talk about ‘pre-habilitation’ to reduce frailty before treatment,” says Greystoke.

Studies have shown that cancer patients with low muscle mass have shorter life expectancy and are far more likely to have side effects from treatment. It’s one area where pre-habilitation could help.

“There are some experimental drugs that may be useful in building up muscle mass, and diet and moderate exercise can help, but all of this needs proper testing,” says Greystoke.

Surgeons have been investigating ways to improve people’s fitness before surgery and help enhance their recovery for many years, says Seymour. But the principles could be extended to other treatments.

“There are some studies now where the patient goes through a geriatric assessment with the geriatrician and oncologist but they don’t stop there. If they identify any issues that can be corrected before treatment, be it fitness, nutritional status or underlying medical conditions, they do it,” says Seymour.

“It’s a bit of a careful balancing act though, because we don’t want to delay cancer treatments unless there’s a very good reason to.”

This can also be difficult to achieve in practice, as hospitals have targets they must meet on the time it takes to start cancer treatment once they’ve decided that treatment is the right option.

Evidence-based treatment

There’s a lot more to learn about how best to treat cancer in older patients. And the only way to get good evidence is through clinical trials.

Clinical trials often have strict rules about who can take part – either based on age, other health conditions, or cognitive ability. Most Cancer Research UK-funded clinical trials don’t have an upper age limit, and when there is one we ask researchers to justify why they’ve made that decision.

But despite there being no upper age-limit in most trials, older patients are still hugely underrepresented.

“It’s all very well saying that there’s no upper age limit in trials, but if a trial includes an arm of standard chemotherapy that I know will cause unacceptable toxicity in an elderly, frail patient then I’m not going to put that patient into the trial. It doesn’t matter what it says in the protocol,” says Seymour.

Trials can also exclude patients with other medical conditions or who are generally unwell for safety reasons, which could mean that older patients can’t take part. In our report on treating and caring for an ageing population, experts highlighted the need for research that examines how to optimise treatments for patients with existing medical conditions, or co-morbidities. Right now, much of this evidence is missing.

“The result of all this is that doctors don’t have the information they need to treat older, frailer patients safely when cancer treatments become standard. We need to start gathering that evidence along the way,” says Seymour.

One way to get the evidence is to run specific trials testing treatments in older patients. Seymour has run a number of these trials, funded by Cancer Research UK, which test different doses of chemotherapy in bowel cancer and now in upper gastrointestinal cancer.

He would like this information to be used to make clinical trials more open in the future.

“Once we’ve established some basic principles for that will allow us to optimise chemotherapy and other types of treatment intensity based on people’s age and fitness, we then need to carry that knowledge forward into clinical trial design.”

Seymour envisions clinical trials being more flexible, allowing doctors to modify the dose of a treatment being used if necessary.

“It would make trials more complicated and it would require quite sophisticated statistics, but it would make trials a lot more open.

“It would help give us the information we need to make sure everyone gets the right treatment for them.”

Michael

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