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The research team of scientists from the University of Birmingham discovered the opportunity for a new treatment by combining three existing drugs, including a commonly-used anti-epileptic, a contraceptive steroid and a cholesterol-lowering agent. Their discovery led to a £1million funding award from Blood Cancer UK to run a randomised clinical trial to test the new drug combo against another experimental agent (Danazol) in patients living with Myelodysplastic Syndromes (MDS).
The scientists already discovered that mixing bezafibrate (BEZ), a drug for lowering cholesterol with medroxyprogesterone acetate (MPA), that this combo eased a range of blood cancers including AML, chronic lymphocytic leukaemia (CLL) and non-Hodgkins lymphoma.
But now, clinical trials have revealed that adding valproic acid to a low-dose combination of the other two drugs ramped up the killing of AML cells.
This gives the low-dose triple-drug combo (VBaP) a cancer-busting impact which is similar to a high dose of BEZ and MPA (BaP).
Co-author Professor Chris Bunce said: “Using existing drugs to treat conditions outside of their approved indications is a proven approach to generate effective low-toxicity therapies.
“We believe that treating patients earlier with low toxicity therapies is the most effective clinical strategy for improving patient outcomes.”
Earlier clinical trials had shown that low doses of BaP given to patients who could not receive chemotherapy produced no toxic side effects and helped patients to boost their production of blood cells.
This could signal a revolutionary advancement in cancer treatments as chemotherapy is often a brutal and rigorous form of treatment with a range of painful side effects.
But doctors will need to be careful, as high doses of the dual combo were not well tolerated due to the frail nature of the patients caused by their age, poor kidney function, disease and, in some cases, prior chemotherapy treatments.
Co-author Dr Farhat Khanim warned: “A major challenge in our previous BaP trials has been the focus on elderly patients for whom more intensive therapies were not an option.
“For many of these patients there are very few treatment options other than regular transfusions to combat life-threatening deficits in red cells and platelets and antibiotic control of frequent life-threatening infections.
“It is, therefore, an attractive option to consider testing VBaP in MDS patients. As the drug combination may have a profound impact on quality of life and survival of these patients.”
Over 7,000 people in the UK have MDS and many patients die because their disease transforms into acute myeloid leukaemia (AML) – an even more aggressive blood cancer.
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The general outlook for AML is poor, but when AML arises from MDS it is even worse.
Left untreated, AML kills patients fast by crippling production of normal blood cells.
The disease is most prevalent in elderly people, many of whom cannot tolerate ‘traditional’ treatment of intensive chemotherapy because of their age and frailty.
The findings of the study were published in the journal British Journal of Cancer.
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