Clearing up chemo options for frail and elderly patients with advanced oesophageal and stomach cancers

The older you are the more likely you are to develop cancer. And more than a third of all cancer cases in the UK each year are diagnosed in people aged 75 and over. But ageing poses a challenge beyond just raising our risk.

As we age, we get frailer. This means that daily tasks, which may seem minor to someone fitter, can really affect those who aren’t as strong as they used to be.And if you bring a diagnosis of advanced cancer and treatment into the picture, it leaves doctors with some difficult decisions to make.

According to Professor Matthew Seymour, from the University of Leeds, there are two options – you either risk potentially making a frail and elderly patient sicker by giving them chemo, or you advise against cancer treatment that could give them precious extra time.

Until now, there’s been little evidence to reassure doctors either way. But new, unpublished results from a Cancer Research UK-funded trial may give some much-needed comfort.

Less treatment, but a better life

Some cancer treatments can be adapted for those not strong enough for a full dose. “But until now that’s usually been done in a somewhat haphazard way,” says Seymour, adding that it’s normally clinical experience, rather than scientific evidence, that guides these decisions.

“There’s a worry that if you give low dose treatment, you’re giving inferior treatment,” he says. But the new, unpublished data, soon to be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in the US, suggests otherwise.

The study included 514 people all over the UK, at an average age of 76, who had advanced stomach or oesophageal cancer. Their doctors knew they wanted to offer chemo, but they weren’t sure of the best dose.

“We randomly allocated patients one of three different doses of chemo,” says Seymour. Instead of the usual trio of chemotherapy drugs that fitter patients receive, people on the trial were given two of the three drugs at the different doses.

The team had previously shown that oxaliplatin and capecitabine were the most effective duo from three standard-of-care chemotherapies. Patients were randomly allocated to receive these two drugs at either full strength, medium-dose or low-dose.

Lowering the dose of treatment didn’t make the chemo any worse at controlling the cancers, or affect how long the patients lived. And when the researchers investigated patients’ experience of treatment, considering factors like the side effects or impromptu hospital visits, and the patients’ own view of how worthwhile their treatment was, the lowest dose chemo group fared best of the three.

“What this trial says is that to give substantially lower dose is not only okay, but it’s absolutely the right thing to do,” says Seymour.

“It means doctors can confidently know that they’re not compromising their patient’s survival and are actually giving them a kinder treatment, which will improve their quality of life.”

These results haven’t yet been critiqued by the scientific community, but Seymour says this unpublished work could quickly start to help doctors tweak the treatment they prescribe their elderly patients.

“Doctors will be able to change their practice based on this trial alone. They will now feel confident to prescribe the lower dose of chemo used in this trial immediately for some patients.”

Redesigning trials for the elderly

Dr Alastair Greystoke, from Newcastle University, also faces treatment dilemmas with his older or frailer patients. He agrees this trial could be practice changing and believes these new data are important for two reasons.

The first is how patients were assessed before taking part. In most cases, cancer doctors use a fitness rating called ‘performance status’ to decide if a patient will be able to tolerate toxic treatment.

“In general, most clinical trials are aimed at people with performance data of 0 to 1 and we normally wouldn’t offer chemo to people who are a 3 or 4,” says Greystoke.

A performance status of 0 means that, apart from having cancer, patients are fit and well. The less active and independent a person is the higher their performance status, with a rating of 4 meaning the person is bed bound.

But Greystoke says this poses a problem.

“The boundaries are often not clear. If someone says: ‘I have to take a quick power nap for 20 minutes a day and then I’m off walking the dog for miles’, how do you grade that?”

For their study, Seymour and the team used frailty scales, as well as performance status, to assess patients. The scales incorporate many different things, not just how active or physically strong someone is. It also isn’t necessarily to do with age, more of a measure of how age has affected someone.  Using measures of frailty may be a better measure of how strong someone is for treatment.

“This study shows that there is benefit in identifying patients who are frail, because you can adjust their treatment to be more tolerable,” says Greystoke, adding that frailty may be a better prediction of how someone will handle cancer treatment overall.

Improving the end of life

The study’s second unique element, says Greystoke, is its focus on quality of life.

“The team asked the patients: ‘Did this treatment go well? Would you take this treatment again if you had the chance?’”

We know when we talk to older cancer patients, survival may not be their top priority.

– Dr Alastair Greystoke, Newcastle University

This study is about patients with incurable cancer who may be in the last months of life. And when you’re supporting people looking for a few extra months with their loved ones, getting these balances right is vital.

“We know when we talk to older cancer patients, survival may not be their top priority,” says Greystoke. In this case, survival or cancer control might, therefore, not be the most important thing for trials like this to measure. Greystoke says this is starting to happen, but it’s early days.

“It’s great that Cancer Research UK funded this trial and that the international community is now accepting the value of studies like this,” he adds.

Leaving a legacy

Seymour hopes that other teams will consider these factors as they design trials for other cancers.

“Hopefully these results will also stimulate similar research for patients with different cancers and using different drugs, to see whether more people in the future could benefit from gentler treatment,” says Seymour.

“A study like this will mean in the future we don’t just assess people’s performance status we assess their frailty as well,” says Greystoke.

And willingness to take part certainly doesn’t seem to decrease with age.

“One of the things we found in this trial was that the prevailing attitude of patients was that they were very pleased to have been asked to be part of research,” says Seymour, who wrote to all the loved ones of patients that took part in the trial to thank them.

In reply, the wife of one man wrote back:

“My family and I would like to say thank you. It’s so good to know that you’re not forgotten. I lost my dear husband of nearly 60 years in May 2015. When he was asked if he would like to take part in the trial, he already knew he was terminally ill. He said: ‘It’ll be too late for me but if it will help others I’ll be very pleased.’ And we hope this too.”

“It’s quite touching,” says Seymour. “Patients who are frail or elderly often think they’re on the scrapheap, so when a researcher says they’re actually very interested in them and would they like to be part of a research trial, we get very positive feedback.”

Gabi