A new way of treating cancer has shown “great promise” in its first clinical trial at the Royal Marsden Hospital in London.
Researchers gave olaparib, a drug being developed by AstraZeneca with the UK Institute for Cancer Research, to 60 patients with advanced breast, ovarian and prostate cancers. All had mutations in the BRCA1 and BRCA2 genes associated with inherited forms of these cancers.
“This drug showed very impressive results in shrinking patients’ tumours,” said Dr Johann de Bono of the ICR. “It is giving patients who have already tried many conventional treatments long periods of remission, free from the symptoms of cancer or major side-effects.”
The results, which have caused a buzz at recent cancer conferences, were published on Wednesday night in the New England Journal of Medicine, the leading US medical journal.
Olaparib kills cancer cells but leaves healthy cells relatively unscathed. The drug blocks an enzyme called Parp, which is involved in repairing DNA defects in human cells. Healthy cells can mend their DNA through alternative biological pathways, but cancer cells carrying the BRCA1 and BRCA2 genes do not have alternative repair mechanisms – and they die in the presence of the drug.
BRCA1 and BRCA2 mutations are responsible for about 5 per cent of breast cancers – though these occur in younger women and tend to be particularly aggressive tumours. The same mutations are also implicated in some ovarian and prostate cancers.
But ICR scientists predict that olaparib and other drugs that work in the same way – known as Parp inhibitors – will also be effective against many non-BRCA cancers that have different DNA repair defects. They believe up to half of the most common type of ovarian cancers could respond to olaparib treatment.
Unlike a competing Parp inhibitor being developed by France’s Sanofi-Aventis, which is injected into patients as an adjunct to chemotherapy, olaparib has the advantage that it is taken on its own by mouth. “It is remarkably free of side-effects,” Dr de Bono said.
The original research on olaparib was carried out at ICR and Sheffield University and taken up by KuDos, a Cambridge biotechnology company that AstraZeneca bought at the end of 2005.
AstraZeneca and ICR are planning more extensive clinical trials to discover how effectively olaparib will fight a wider range of other non-BRCA cancers. “Parp inhibitors are going to change cancer medicine,” said Dr de Bono.
The researchers warn that olaparib must complete several more years of testing in patients before it becomes commercially available. It will then be accompanied by a genetic test to identify patients who will benefit from the drug.
The Financial Times