Cancer Research UK leads global lung cancer drug trial

Cancer Research UK

Cancer Research UK scientists in Oxford are trialling an experimental drug to treat lung cancer patients who have stopped responding to initial chemotherapy treatment. The trial will take place at the Oxford Radcliffe Hospitals NHS Trust.

The international early Phase II trial led by a team based at the Oxford Cancer Research Centre will trial the experimental drug called LY2181308 with advanced non-small cell lung cancer patients who no longer respond to platinum chemotherapy - the standard initial treatment for this group.

LY2181308 blocks the ability of cancer cells to make a protein called survivin which instructs cells to grow - and crucially prevents cell death. This combination of ‘immortal’ cells with uncontrolled growth leads to cancer.

Raised levels of survivin are frequently found in tumours, and preventing its production kills cancer cells. It is rarely found in healthy tissue so the drug only targets cancerous cells – this is key in reducing side effects.

The trial consists of two elements. One group of patients will receive docetaxel on its own – the normal standard of care after platinum treatment. The other group will receive LY2181308 alongside docetaxel.

This is one of the first trials taking place at the new Oxford Cancer Research Centre, bringing together Oxford Radcliffe Hospitals, the University of Oxford and Cancer Research UK to develop new treatments for cancer patients and to bring them to patients as soon as possible.

Trial chief investigator, Dr Denis Talbot, consultant medical oncologist at Oxford Radcliffe Hospitals and the Cancer Research UK clinician at The University of Oxford, said: “It’s greatly encouraging that we’re able to take this new experimental drug to treat lung cancer into further development. We hope that it may increase survival rates for lung cancer patients.

“Survival from this disease still remains low. One reason is that the majority - 65-75 per cent - of lung cancer patients are diagnosed when the cancer has already become aggressive, which makes it more difficult to treat successfully. There’s an urgent need to develop new medicines which may provide additional options for these patients.

“We’ll look forward to the results of this trial with great interest.”

Survival rates for all types of lung cancer are still low. Fewer than 10 per cent of lung cancer patients survive the disease beyond five years after diagnosis.

Non-small cell lung cancer accounts for around 85 per cent of all lung cancer cases. Around 30,000 people are diagnosed with this form of the disease each year in the UK.
Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “We’ve made progress in recent years to discover new ways to tackle lung cancer and this important trial brings further opportunities for this hard to treat disease.
“We were involved in the development and testing of several drugs commonly used to treat the disease including cisplatin and carboplatin. And it’s exciting to be leading on the research to test a new potential drug which we hope will one day help increase the survival rate for lung cancer patients.”

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Notes to Editor

The international trial will run till 2012. The trial will run at five UK centres in London, Nottingham, Oxford, Aberdeen, Sheffield and Manchester. It will also run at nine US centres, and several centres across Belgium, Germany, Italy and Poland.

  • More information on the trail on CancerHelp UK

LY2181308 is owned by Eli Lilly and Company Limited which is funding the trials. The trials are managed by ICON plc. 

LY2181308 is an antisense oligonucleotide which blocks the messenger ribonucleic acid (mRNA) required to make survivin. mRNA is the genetic information needed to translate genetic information into proteins essential for life. The molecule was originally developed by Isis Pharmaceuticals in Carlsbad/CA. 

Pre-clinical work

Part of the pre-clinical work for the development of the drug was carried out at Oxford University by Cancer Research UK scientist Dr Denis Talbot and his team. This work showed that the drug was effective in lung cancer cells.

Dr Talbot’s team analysed biopsies from these patients before and after they received the drug. They developed techniques in the laboratory to prove that survivin levels went down in lung cancer patients receiving the drug.

This work was part-funded by the Oxford Experimental Cancer Medicine Centre. 

Docetaxel is one of two standard chemotherapy treatments used in patients whose disease has progressed after they have already received platinum-based chemotherapy. The majority of these patients relapse three to six months after this initial therapy. Docetaxel blocks a protein called Bcl-2 which prevents the cell destroying itself when it is faulty.

Pemetrexed is an anticancer drug used to treat patients whose cancer has progressed following first line – initial – chemotherapy. A third approved treatment is an epidermal growth factor (EGFR) inhibitor, called erlotinib.