Testing times: Vicki Searle and her son Henry, who was diagnosed with an inoperable brain tumour when he was 19
We tend to associate breakthrough treatments with new — and often unaffordable — drugs.
But it seems a remarkable improvement in the survival time of patients with brain cancer has been achieved using a combination of four old drugs (a statin, a diabetes pill, an antibiotic tablet and a dewormer) that cost just £400 a year.
Results from an ongoing trial run by the private Care Oncology Clinic in London suggest that giving this new combination treatment doubled the average sur- vival time.
Survival rates for brain tumours have remained unchanged for at least 20 years, when the brain cancer drug temozolomide came on to the market. Around 15 per cent of adult patients survive for more than five years after diagnosis. For glioblastoma, the most aggressive type of brain cancer, the figure is between 6 and 10 per cent.
The new study involved nearly 100 patients with glioblastoma — the fast-growing type of brain cancer affecting politician Tessa Jowell — treated at the clinic over three years with the combination treatment, as well as radiotherapy and chemotherapy.
The average survival time for glioblastoma is estimated to be between eight and 14 months — the average survival time for the patients given the new combination treatment was 27.1 months.
Earlier this year Tessa Jowell spoke movingly in the House of Lords to highlight the lack of funding for research into brain cancer — she suggested that the survival rates reflected the fact that less than 2 per cent of UK cancer research funding goes to this area.
Developing a new cancer drug can take ten years, and the cost for treating one patient can be deemed prohibitive — one of the latest cancer drugs, pembrolizumab, used for advanced melanoma and lung cancer, costs nearly £100,000 a year. The drug cocktail used at the Care Oncology Clinic is available now and costs only a few hundred pounds.
One of those who’s been treated with it is Henry Searle who was diagnosed with glioblastoma just over three years ago at the age of 19.
It was discovered too late for surgery, and even with chemotherapy and radiation therapy, he was expected to live for only 14 months.
Alarmed by these odds, Henry’s parents — Vicki, who works in the tourism industry and Jonathan, a chiropodist — were determined to give him every chance, and despite objections from his oncologist, they got him started on the drug cocktail which had just become available at the clinic.
Defiant: His oncology team told him that even with the ‘gold standard’ treatment (chemotherapy and radiotherapy) he was only expected to live for 14 months
Two years after Henry’s diagnosis, his NHS consultant wrote to the family to say there was ‘no evidence of active disease’ and that Henry didn’t need further cancer treatment.
Henry is still on the drug cocktail (the last time he had chemotherapy was in 2015) and today his scans show the tumour is no longer growing. And the cost of this life-changing treatment? Between £200 and £400 a year plus £1,000 for four consultations.
It involves four old — therefore cheap — drugs long used for other conditions and so considered safe. Two are among the best-selling medications in the world: atorvastatin, a type of statin, and the diabetes drug metformin.
The other two are an antibiotic, doxycycline, used for dental infections and acne, and mebendazole, a deworming pill. So how could this apparently random combination of drugs reduce tumours?
What links them is that in various ways they interfere with a tumour’s ability to absorb or use the resources they need to grow. The way the body controls energy is known as metabolism. The metabolism of cancer cells is different from the one that powers healthy cells.
Cancer cells need much greater amounts of glucose, the form of sugar our bodies use for energy. So making it less available, which metformin in particular does, means that the drug combination is effectively starving the cancer cells.
Weakened by the energy drop they become more vulnerable to attack by the chemotherapy and radiotherapy routinely used to treat cancer.
Miracle: Two years after Henry’s diagnosis, his NHS consultant wrote to the family to say there was ‘no evidence of active disease’ and that Henry didn’t need further cancer treatment
The idea behind this approach to cancer is known as the metabolic theory — meaning it deals with the use of energy in the body. Because the drug cocktail targets the way cancer cells get their growth factors and raw material for making energy, it has the potential to be effective for a variety of cancer types.
The drug cocktail was put together by the Care Oncology Clinic’s co-founder Dr Robin Bannister, a research scientist, from a list compiled by the clinic’s researchers trawling through thousands of studies on licenced drugs that were also shown to have anti-cancer properties.
The normal route for testing a new treatment is what’s called a randomised controlled trial, where it is compared against an alternative, often a placebo. As the patents on the drugs in the new cocktail have run out, there is no incentive for the drug companies to do these (expensive) trials.
Instead, the results were based on what’s known as a ‘service evaluation’, where data is gathered from patients in a real-world setting as approved by the Medicines and Healthcare products Regulatory Agency — the UK drug watchdog.
The clinic plans to use this data to supply NICE with the evidence it needs to make the treatment available on the NHS. ‘Giving these safe drugs to patients in a real-world trial allows us to gather valuable information on how they impact on cancer,’ says Robin Bannister.
One of the clinic’s oncologists, Dr Padman Vamadevan, who has previously worked in the NHS, says the results are ‘slowly changing the attitudes among consultants whose patients attend the clinic’.
‘When we started, not many oncologists were familiar with treating the metabolic features of cancer, so they were sceptical,’ he says. ‘But now patients report that their doctors are genuinely interested in this research as they see the apparent benefits.’
Combination: Because the drug cocktail targets the way cancer cells get their growth factors and raw material for energy, it has the potential to be effective for a variety of cancer types
Dr Lucinda Melcher, a clinical oncologist at the North Middlesex University Hospital in Edmon- ton, admits that she was not initially convinced.
Her husband Adam Blain, a 48-year-old lawyer, has glioblastoma and having had all the NHS had to offer, he began treatment at the clinic over three years ago.
‘I was sceptical at first because their drug regimen was then not backed up by any evidence but the team there was obviously professional and committed and the treatment is scientifically plausible,’ says Dr Melcher.
Adam, a father of three, who is still on the drug cocktail, has had to stop working but has a good quality of life, although his short-term memory is poor, says his wife.
But while Dr Melcher is delighted her husband has beaten the odds, she is not convinced that it was due to the drug combination.
‘It could still be chance,’ she says. ‘It’s possible that Adam is one of the 10 per cent of these patients who survive five years on the standard treatment, especially since his tumour was completely removed which improves your chances.’
Robin Bannister points out that: ‘Every oncologist has their own list of “miracles”; people who have lived far longer and better than was expected.
‘And that is why we need to conduct studies with enough patients to make sure the chance element can be accounted for.
‘The hundred people treated in this trial makes it one of the larger studies ever done with glioblastoma.’ (This compares with one of the trials for temozolomide, which involved over 500 patients.)
The study is continuing. The next step is to compare the results of the nearly 100 glioblastoma patients treated at the clinic with a closely matched group of NHS patients who only received the standard treatment of radiotherapy and chemotherapy.
The results will make the findings of the trial more reliable and are expected to be published in a journal later this year.
For more information, visit: careoncologyclinic.com
EXPERTS WHO THINK A HIGH-FAT DIET CAN FIGHT BRAIN TUMOURS
Raffi Kalamian Walsh was just four when a routine eye check picked up a worrying change and he was diagnosed with brain cancer.
Over the next 14 months, Raffi was given weekly chemotherapy followed by 12 weeks of a different chemo drug followed by two operations to remove part of the tumour. Two months later a scan showed it was back and spreading.
‘I can’t begin to describe how devastating it was to watch our young child being taken apart, piece by precious piece,’ says Raffi’s mother Miriam, who, with her husband, Peter, had adopted Raffi when he was two.
Tragic: Raffi Kalamian Walsh was just four when a routine eye check picked up a worrying change and he was diagnosed with brain cancer
Three years after his diagnosis Raffi began treatment with a combination of five cancer drugs. ‘Within weeks my normally cheerful little guy was nauseous, fatigued, and unable to focus,’ recalls Miriam.
‘When he opened his mouth to speak, all that came out was gibberish.’ While searching for information about Raffi’s drugs, Miriam stumbled on a radically different approach to cancer, based on the idea that a very high fat, low carbohydrate diet could slow tumour growth. It was being investigated by Professor Thomas Seyfried, a biochemistry researcher at Boston University.
Miriam explains: ‘Professor Seyfried had shown it was possible to slow the growth of brain tumours in mice.
‘I knew it was not yet tested in people, but Raffi desperately needed something different.’ Surprisingly her son’s doctors agreed.
The five cancer drugs were stopped and within three months Raffi’s tumour had shrunk by almost 15 per cent. He returned to being a talkative, energetic little boy.
The ketogenic diet involves avoiding foods containing sugar: sweets, biscuits, puddings, along with grains, pasta and bread, even wholegrain types, plus starchy vegetables such as potatoes or cooked carrots, as well as all legumes, beans and pulses.
Instead the diet is built around fats including butter, cream, coconut oil, olive and avocado oils and some omega 3 oils, small portions of protein such as meat, fish or eggs, as well as salad and non-starchy vegetables (such as broccoli and green beans).
Strength: Over the next 14 months, Raffi was given weekly chemotherapy followed by 12 weeks of a different chemo drug followed by operations to remove part of the tumour
Fruit is limited to berries, as these are low in sugar. The aim is to starve cancer cells of glucose, their preferred fuel. Lacking carbohydrates the body burns fat instead and your liver starts pumping out substances called ketones which can replace glucose as fuel for the brain and muscles.
Crucially, however, tumours can’t use ketones as fuel.
Miriam concedes Raffi struggled with social events: ‘because there were cakes and sweets everywhere,’ she says. ‘But that was a walk in the park compared to what he had endured in terms of gruelling treatments.’ During his first nine months on the diet Raffi also received a low dose of chemotherapy drug, before relying just on the diet.
The odds against Raffi were daunting — at his diagnosis doctors said he had a one in three chance of any response to treatment.
‘The first three years on the diet were phenomenal,’ says Miriam. ‘He seemed almost completely well again.’
Raffi remained on the diet for six years. ‘Much of the time he was living pretty normally,’ Miriam says. ‘In contrast, children with brain tumours following the standard protocol often undergo treatment after treatment until the end.’ Dr Nelofer Syed, a senior research fellow and lecturer in cancer biology at Imperial College London, agrees the ketogenic diet has great potential.
‘Early research shows that it can improve the effectiveness of both chemotherapy and radiotherapy and that cancers find it difficult to use ketones for energy,’ she says.
Loss: He died nine years after he was diagnosed, at the age of 13 in April 2013
She is the co-author of an article summarising research on the diet, published last year in the journal Frontiers In Molecular Neuroscience.
It reported on lab studies showing the diet could, among other things, reduce the ability of tumours to hook up to a blood supply and make it harder for cancer to spread. However as yet, there have been no big studies testing the diet against other therapies, and Cancer Research UK does not recommend it as an alternative to the standard healthy balanced diet.
‘We’d all love better evidence,’ says Dr Syed, ‘but providing patients do it under the supervision of a dietitian who is trained in delivering it, I think it is worth trying.’
The ketogenic diet is already approved by NICE for children with epilepsy; a big randomised trial for childhood epilepsy showed it could reduce or even stop the seizures.
Ultimately, however, the diet couldn’t save Raffi. He died nine years after he was diagnosed, at the age of 13 in April 2013.
Not every patient will benefit as dramatically as Raffi did and his success doesn’t ‘prove’ the diet works. ‘Its value is as an add-on to what you’re already doing with your oncology team,’ says Miriam. She adds: ‘The diet kicked the can down the road for six years.
‘During a period when most people with cancer are in clinics or hospitals, Raffi was out riding his trike.’
Keto For Cancer by Miriam Kalamian (Chelsea Green, (£18.99).