Medium and lower doses of chemotherapy were as effective as the full-strength dose at controlling disease for elderly or frail patients with advanced cancer of the stomach or oesophagus and leads to fewer side effects such as diarrhoea and lethargy.

These are the results of the GO2 trial, a Cancer Research UK funded study, that could change the standard of care for patients who can’t have full dose chemotherapy due to their age, frailty or medical fitness.

The study, which ran at hospitals all over the UK, coordinated from the University of Leeds, involved 514 people with stomach or oesophageal cancer. Their average age was 76 and the oldest was 96 years old. All were either frail, elderly or medically unfit, and for those reasons would be unlikely to tolerate full-strength treatment, which involves three chemotherapy drugs.

Lowest dose treatment best for quality of life

Patients went through a careful medical assessment, then went onto chemotherapy with just two drugs and were allocated at random to receive them at either full-strength, medium-dose or low-dose. They were then carefully monitored to see how well the cancer was controlled, whether they had symptoms and side-effects, whether they felt their treatment was worthwhile, and what overall effect it had on their quality of life

The researchers reported that the medium and lower doses of chemotherapy were as effective as the full-strength dose for controlling the cancer. But when the researchers looked at the overall effect of treatment, including quality of life, they reported that it was the lowest dose treatment that came out best.

Around 15,800 people in the UK are diagnosed with stomach and oesophageal cancers every year. Almost half (45%) of these people are 75 and over. By 2035, this proportion is projected to rise to 55%, because of the UK’s ageing population. This study is one of few phase III trials in the country that seek to address how to best care for and treat this increasing population of elderly or frail cancer patients.

These findings also open up the possibility of more older and frail patients being able to take part in clinical trials.

Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “These valuable results reduce fears that giving a lower dose chemotherapy regimen is inferior and could make a huge difference for patients with stomach or oesophageal cancer who can’t tolerate intensive courses of treatment.

“Older or frail patients are often not considered for new drug trials or standard of care therapy as they’re less able to tolerate combination chemotherapy. These trials are critical to provide much-needed evidence on the effectiveness of new therapies and combination approaches, helping us develop new treatments for this growing group of patients.”

The researchers also assessed whether there were differences for the patients in the study who were under 75, or less frail, who might be expected to benefit from stronger treatment; but will be reporting that the lowest dose treatment gave the best results for them as well.

Sparing side effects

Professor Matt Seymour, co-chief investigator at the University of Leeds and Leeds Teaching Hospitals NHS Trust said: “When we’re treating people who are elderly or frail, we are especially conscious that treatment can have harmful as well as beneficial effects. Doctors often prescribe reduced doses of drugs, or sometimes no chemotherapy at all, based on their clinical experience, but until now there has been little hard evidence to help them in those decisions. Our results provide that evidence, so doctors can confidently give people a lower dose of chemotherapy, sparing them side effects without worrying that it’s compromising their chance of survival.

“We hope this approach can be applied in other disease types so that more work can be done to improve both survival and quality of life for elderly and frail patients.”