Pioneering cooling boots and mittens to help stop painful chemo side-effect

Brian Conroy is used to the cold nipping at his fingers and toes after a lifetime in construction work and fishing in all weathers at weekends. But his hands and feet are now being deliberately cooled in a clinical trial – the first of its kind in the NHS – looking at reducing one of the most debilitating side-effects of chemotherapy: peripheral neuropathy.

This type of nerve damage can cause constant pain, as well as a tingling sensation, weakness or numbness, in the fingers and toes.

While for some the side-effect is short term, in many others it lasts for months, years or becomes permanent.

If fingers are affected, it can make everyday tasks difficult, particularly fiddly ones such as doing up buttons. And with toes, it can cause balance problems, meaning patients have to rely on walking aids.

Some research suggests more than two-thirds of patients suffer chemotherapy-induced peripheral neuropathy – and a 2019 study in the journal Pain reported about 30 per cent of patients will still be living with it a year or more after finishing chemotherapy.

Dr Rick Walshaw, a consultant clinical oncologist at the Clatterbridge Cancer Centre in Liverpool, who is leading the new trial, explains: ‘Several chemotherapy drugs can cause peripheral neuropathy, because they damage the tiny nerve endings that supply the skin in the fingers and toes.’

Indeed, it is a side-effect of some of the most common chemotherapy drugs, used for multiple cancer types. These include the taxanes, such as paclitaxel, often used to treat breast, ovarian, prostate and lung cancers; as well as alkylating agents, including oxaliplatin, used to treat colorectal, stomach or pancreatic cancers.

Peripheral neuropathy can seriously affect patients’ quality of life, explains Dr Walshaw. ‘A significant proportion can suffer with it years after finishing chemotherapy – even if their cancer is in remission. It can be very stubborn to treat once it has occurred.’

He adds: ‘It also has a cumulative effect – so it may not be obvious after the first one or two cycles, but the longer patients take the drug, the more damage it can cause.

‘Currently, if a patient gets peripheral neuropathy during treatment, then the dose of oxaliplatin, for instance, has to be reduced or even stopped. Potentially, this means we are not going to control the cancer as well.’

Anecdotal evidence suggests exercise, like squeezing a squashy ball, can improve symptoms in some patients, possibly by reducing inflammation.

Dr Walshaw adds: ‘Antidepressants and anticonvulsants can lessen the pain of peripheral neuropathy, as these drugs increase brain chemicals which can affect pain signals – but there are no drugs to prevent or cure it.’

Brian, 64, is being treated with oxaliplatin following a bowel cancer diagnosis earlier this year, and has already had two of his four chemotherapy treatment cycles (these are given every three weeks: his treatment will end in January), when he also had the hand-cooling therapy.

Before he was diagnosed, Brian had been suffering from diarrhoea for two months and had been taking daily loperamide, an over-the-counter tablet, to control it. When he spoke to his GP surgery about having this on a regular prescription, it was suggested he make an appointment to see his doctor.

‘They said my symptoms needed investigating,’ recalls Brian, who lives with his wife in Birchwood, near Warrington, Cheshire.

After examining Brian, his GP referred him for an endoscopy, where a tiny camera is used to examine the bowel. ‘It found a tumour and they said this was highly likely to be cancerous,’ says Brian. ‘I was shocked as up to then I had been pretty blasé.

‘The first thing I said was, ‘Where do we go from here?’ ‘

In September, Brian had a CT scan, which showed the cancer had not spread. He underwent surgery within two weeks and ‘just felt glad to be alive’, he says. Then, before starting three months of chemotherapy, Brian was asked if he wanted to join the trial.

He says: ‘I was keen to be involved because I’m self-employed in the building trade and want to continue to use my hands and my feet as normal once I’m recovered so I can get back to work as soon as possible.’

Half an hour before each chemo session begins, he puts on specially adapted boots (similar to ski boot liners) and mitten-style gloves, keeping them on while the oxaliplatin is delivered via a drip in his arm (in his case for two hours), while he sits in a chair.

Cold water is pumped into the gloves and boots via tubes running through them; the temperature is maintained at around 15c.

It is thought that when hands and toes are cooled, the blood vessels constrict, meaning less chemotherapy drug reaches them.

The approach is not dissimilar to the use of cold caps to reduce hair loss during certain types of chemotherapy – this cooling process cuts blood flow to the scalp, reducing the amount of drug reaching this area, preventing hair loss.

Research published earlier this year in the Annals of Oncology showed promising results for the hand and foot cooling system.

The study in Belgium, which used the same kit supplied at the Clatterbridge, compared side-effects in 77 patients receiving oxaliplatin with and without cooling. After 12 weeks, the patients in the control group (who didn’t have the cooling therapy) had 20 per cent more peripheral neuropathy in their hands or feet compared with those who wore the cooling gloves and boots.

Similar results were found after 24 weeks, with the study concluding the treatment was generally well tolerated by patients.

The UK trial came about after medical student Emily Kelly, who was on placement at the Clatterbridge, spoke to Dr Walshaw about her mother Barbara’s experience of bowel cancer treatment. Barbara had done her own research and read about how cooling her hands and feet – which in parts of Europe is also used for breast cancer patients – could help her lessen these common side-effects.

Dr Walshaw’s team looked into the practicalities of keeping a patient’s hands and feet cool while having chemotherapy and borrowed two cooling systems from the equipment’s manufacturer, Hilotherm.

As the loan was for only five months, it was decided to use the machines on bowel cancer patients having oxali- platin, as the treatment fits into that timeframe.

‘This ongoing study is about the feasibility of delivering this treatment without causing significant disruption,’ says Dr Walshaw. ‘We want to ensure it is not too cumbersome for the patients and that the staff can easily apply it.

‘A few years ago, the cold cap technology started out like this,’ says Dr Walshaw. ‘That also was tried on only a few patients in clinical trials – but today it’s standard care for many.’

If the new study, which will involve 25 patients with bowel cancer being treated at the Clatterbridge’s Wirral and Halton clinics, proves successful, then the approach will be trialled in different cancers and with different chemotherapy drugs. The current study is due to end in March.

Dr Duncan Gilbert, a consultant oncologist in lower gastrointestinal cancers at University Hospitals Sussex NHS Foundation Trust, welcomes the new trial.

‘Peripheral neuropathy can be a major problem for patients. Its effects can be lifelong and given that many of these patients will be cured of their cancer, this can represent a life-changing side-effect.

‘So looking at cooling aids like this to improve long-term healthcare is very welcome.’

Brian’s experience of the new kit so far has been promising.

‘I didn’t have any tingling in my hands and toes after my first two sessions of chemotherapy which was good. And the temperature is not unpleasant, only a bit cold – like going out on a winter’s day without gloves on,’ he says.

‘If this can stop the pins and needles being a lasting side-effect, it’s certainly worth doing.’