Wonder drug extends life for cancer patients
A REVOLUTIONARY cancer treatment has been shown to shrink tumours by a third.
George Alagiah returns to BBC News after cancer treatment
The drug therapy was applied in tests to patients who had been through all the other options. In trials, more than half of ovarian cancer sufferers and a third with lung cancer were given precious extra time after receiving the previously untested drug combination.
In each case the disease had become resistant to chemotherapy alone but the new therapy stopped cancers growing for an average of six months.
The “exciting” results from tests carried out in Britain have given hope to patients who have become resistant to standard treatments that they can live longer than expected.
Study leader Professor Udai Banerji, of London’s Institute of Cancer Research (ICR), said: “We combined chemotherapy with a targeted drug which blocks the way cancer cells react to treatment in order to survive.
“What we saw was very exciting – these are patients who had exhausted all other options.”
Scientists are finding promise in combining drugs, or using them with treatments like chemotherapy or radiotherapy, to attack cancer and make it harder to evolve resistance.
In the latest development researchers combined the drug vistusertib with chemotherapy and found it was successful in blocking the way cancer cells react to treatment in order to survive and spread.
Early tests far exceeded what was expected in patients in advanced stages of the disease who had already become resistant to chemotherapy. Preliminary results from the study, led by ICR and The Royal Marsden NHS Foundation Trust, were so good a larger phase II trial is under way which scientists hope will pave the way for a fast-tracked treatment.
Dr Susana Banerjee, Consultant Medical Oncologist at The Royal Marsden who is leading the phase II trial, said: “Effective treatment options for women with relapsed ovarian cancer are limited so these results are very encouraging.
Effective treatment options for women with relapsed ovarian cancer are limited so these results are very encouraging
“In the larger trial we recruited 140 women with relapsed ovarian cancer to standard [paclitaxel] chemotherapy or paclitaxel in combination with vistusertib. We need to wait for these results to see how effective this approach is compared to chemotherapy alone.”
Researchers at the ICR, The Royal Marsden and nine other centres across the UK tested the combination on 25 women with high-grade, serious ovarian cancer and 40 patients with squamous non-small cell lung cancer.
All those who took part in the study had advanced cancers that had spread and in each case standard chemotherapy treatment had failed. Scientists initially tested if the drug combination was safe and found it was well tolerated with manageable sideeffects.
But crucially they also looked at the effectiveness of the combination and found 52 per cent of ovarian cancer patients and 35 per cent of lung cancer patients had a reduction of at least 30 per cent in the size of their tumours.
For each of these cancers the combination stopped growth for an average of 5.8 months. Although drug combinations, which aim to improve the probability of successful treatment, are not new, this particular pairing has excited scientists.
The idea for the combination came about after a previous study found chemotherapy-resistant ovarian cancers typically have high levels of a molecule called p-S6K. This helps cancer cells grow quickly and those behind the tests think this may help cancer resist the effects of chemotherapy.
In the trial patients were given 80mg/m2 of paclitaxel with 50mg of vistusertib twice daily for three days over six weeks. Scientists say the combination therapy has “promise”. Vistusertib works by targeting proteins known as mTOR1 and 2 which “turn on” p-S6K.
By combining vistusertib with chemo, cancer cells cannot use p-S6K to grow and resist treatment. In 2016 a total of 4,227 women in the UK died out of the 7,270 diagnosed with ovarian cancer.
The same year 46,388 people were diagnosed with lung cancer, of whom 35,620 died. ICR chief executive Prof Paul Workman said: “Drug combinations hold huge promise for tackling cancer’s adaptation, evolution and drug resistance.”
Dr Ian Walker from Cancer Research UK said: “We’re pleased to see such promising early results.”
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How star Pierce Brosnan lost his wife and daughter to the cruel disease
Actor Pierce Brosnan has spoken candidly about how ovarian cancer cut short the lives of both his wife and daughter, writes Giles Sheldrick.
The Hollywood star lost first wife Cassandra Harris when she was just 43 in 1991 before Charlotte was taken by the “wretched, inherited disease” at 42 in 2013.
In a remarkably honest assessment of how he views life he said: “I don't look at the cup as half full, believe me.
“The dark, melancholy Irish black dog sits beside me from time to time.
“To watch someone you love have his or her life eaten away bit by bit by this insidious disease, that kind of sorrow becomes an indelible part of your psyche.
“I held the generous, strong, beautiful hand of my first wife Cassie as ovarian cancer took her life much too soon.
“And I held the hand of my funny, wonderful daughter Charlotte before she, too, died from this wretched, inherited disease.”
Ovarian cancer can be caused by faults in the breast tumour suppressor genes. Just over half of all ovarian cancer cases in the UK each year are diagnosed in women aged 65 and over.
About 7,300 women are diagnosed in the UK each year making it the sixth most common cancer in women.
Pierce, 65, who starred as British spy 007 four times, has been married to Keely Shaye Smith, 54, since 2001.
The Roman Catholic father of five has previously told how he found solace in his faith to help him “survive the pain” after Charlotte’s death.
He said: “That’s all you have left when your heart is just a dark hole at four in the morning and you have the weight of the world on your shoulders. No one can escape life’s pain. That’s life.”
I can now plan my life
Anne Goward has already benefited from a similar medical technique mixing drugs with chemotherapy.
The mother developed stage three high-grade ovarian cancer in 2015.
After surgery, she started chemotherapy and for 18 months, it looked as though the treatment had been a success. But the disease returned in 2017.
Initially, renewed chemotherapy went well but complications arising from a blood clot meant she had to stop.
When she restarted, her tumour markers continued to rise and it appeared her body had become resistent to chemotherapy and hope of keeping the disease at bay was fading.
But her doctor recommended that Anne, 54, from Canvey Island, Essex, start a relatively new, targeted treatment called Olaparib, developed by scientists at the University of Cambridge specifically to treat those who have a mutation of the breast cancer suppressor gene.
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Anne, who is married with a 17-year-old son and four step-children, takes sixteen 50milligram tablets every day - eight in the morning and eight in the evening - but despite the high doses, the drug, known as a PARP inhibitor, has given her a new lease of life.
She visits her oncologist every 28 days for a blood test and is given a new course of treatment.
Anne, a bank administrator, said: "My body had become resistant to chemotherapy and I thought that was it. I was living month to month but now I have hope and I can make plans, like booking a holiday. "Within one month of starting Olaparib, my tumour markers had gone down by one third and they are now the lowest they have been in 18 months.
"This targeted therapy is nowhere near as brutal as chemo and although I feel fatigued I have got my life back.
"Chemotherapy resistance means trials to test targeted drugs and drug combinations are vital.
"This drug started to work within 28 days. Before I started this course of treatment I was thinking I maybe only had a few years left.
"But this shows research pays off and there is plenty of reason for people with cancer to be optimistic."
The search for cures
BREAST CANCER
The Cambridge Personalised Breast Cancer programme uses advances in genetics to map tumour DNA, allowing doctors to tailor patients’ treatment plans and helping to spot early on when a tumour is regrowing.
PROSTATE
The STAMPEDE trial aims to find the best treatment for men newly diagnosed with advanced prostate cancer. More than 10,000 have taken part in tests run by University College, London and Cancer Research UK
LUNG CANCER
The National Lung Matrix trial is looking at a number of new drugs to treat non-small cell lung cancer, the most common type. A second phase trial is recruiting people who can’t have surgery or radiotherapy.
BOWEL CANCER
The FOCUS4 trial is testing treatments for tumours that can’t be removed with surgery or have spread to other parts of the body. Patients are treated during a break from chemotherapy to see if it slows tumour regrowth
BRAIN TUMOUR
The ReoGlio trial is looking at whether a common virus that causes coughs and colds could help treat glioblastomas, one of the most common types of brain tumour in adults. Scientists think Reolysin can kill cancer cells.
PANCREATIC
The PrecisionPanc study will analyse the DNA of individual tumours to learn more about the disease and pave the way for clinical trials matching patients’ tumour biology to the type of treatment they receive.
MOUTH & THROAT
PATHOS hopes to offer gentler post-surgery treatment to oropharyngeal cancer patients. Chemo and radiotherapy can help prevent cancers returning but may cause severe longterm side effects.
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Comment by Udai Banerji
Cancer drug resistance is one of the greatest challenges facing us as researchers.
In fact, it's one of the greatest for 21st century medicine.
In the past 20 years, researchers have discovered and developed a new generation of drugs that target specific genes in cancer cells.
Some of these targeted drugs have been spectacular successes, such as trastuzumab (Herceptin) for breast cancer, while others have added extra months of life for many thousands of people with cancer, giving them precious time to spend with loved ones.
However, we've found that cancer can often adapt and change over time to resist standard treatments, eventually rendering them ineffective.
So we've started to look for ways to make new treatments smarter, to counteract drug resistance.
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Through research in the laboratory and in clinical trials such as this one, we have found that one of the best strategies lies in putting treatments together in combination.
We are using our knowledge of how tumours develop and grow to find new treatments that can combine to have an effect greater than the sum of their parts.
We are combining different sorts of treatments - targeted drugs together, or with other treatments such as chemotherapy or radiotherapy. These attack cancer in several different ways at once, making it harder for the disease to evolve resistance.
In this trial we found that in over half of the women with ovarian cancer, a new targeted drug in combination with standard chemotherapy could shrink tumours and slow the progression of advanced cancer.
We also saw positive results in patients with advanced lung cancer.
It's exciting and provides a very promising example of the potential of combination treatments for patients who have stopped responding to standard treatment.
But it's an early trial and so this drug will need to go through bigger trials to show its effectiveness before it might become available more widely. As more combination treatments prove their potential, it is important to keep their costs under control. In the end, we need to ensure that the best treatments get to the patients who so desperately need them.
• Professor Udai Banerji is Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust.