Newcastle University

STI571 is used to treat chronic myeloid leukaemia (CML) and it targets a genetic abnormality in the leukaemia cells called the Philadelphia chromosome.

Unlike other anti-cancer drugs, STI571 selectively switches off signal proteins related to the Philadelphia chromosome in the leukaemic cell, leaving normal cells unharmed.

The new data, to be merged with results from the Hammersmith Hospital in London and other trial centres in the UK and world-wide, will be a huge international talking point when presented to the meeting of the American Society of Hematology (ASH).

Results from trials of the drug have been outstanding and doctors describe them as "very exciting".

One study, which incorporates the Newcastle data, shows that about one third of patients who took STI571 for six months had no evidence of leukaemia (see journalists' note 4). These patients had previously failed treatment with the current 'standard' therapy, interferon. Such results have not been seen with any form of drug therapy in this disease previously.

STI571 was first given to a patient in the UK in September 1999 at the Royal Victoria Infirmary in Newcastle. It was developed in Switzerland by the drug company Novartis and the first clinical trials took place in the United States under the leadership of Professor Brian Druker, the doctor who pioneered this treatment.

About 4,000 people in Britain have CML, and UK doctors see up to 800 new cases every year. The disease kills, and patients have an average of five years to live following diagnosis. The average age of onset is about 55 years.

The only cure for the disease to date is a bone marrow transplant, but because there are considerable risks to patients and a shortage of donors, only 15% of people with CML benefit from this option.

Daily injections of interferon have been the alternative treatment but although this drug prolongs survival it has many side effects, the commonest of which are flu-like symptoms.

Side effects with STI571 are relatively minor, many patients have no side effects at all, and the drug is easy to take. Patients take between four and six capsules per day by mouth. In contrast to conventional chemotherapy, there is no infertility, and no hair loss.

Dr Stephen O'Brien, senior lecturer/consultant with the University of Newcastle's Department of Haematology, is leading the trials in Newcastle in collaboration with Dr Anne Lennard, also a senior lecturer/consultant and Professor Stephen Proctor, head of the Department of Haematology. The Newcastle team have been working in close collaboration with a team at the Hammersmith Hospital in London led by Professor John Goldman, an international leader in the treatment of CML.

Dr O'Brien says while the results are positive, they need to be viewed with an element of caution.

"As yet, we don't know how long responses to STI571 will last or whether these patients are cured. We need results from five years of clinical trials before we get enough information to be confident that this drug improves survival for leukaemia patients".

"However, STI571 clearly represents a major breakthrough in the treatment of chronic myeloid leukaemia and paves the way for the development of new types of anti-cancer drugs that could improve survival whilst offering minimal side effects and good quality of life."

CONTACTS:

1. DR STEPHEN O'BRIEN will be available for interview in San Francisco from 2pm to 3pm UK time ONLY: You can contact him at the Mandarin Oriental San Francisco Tel: 001 415 276 9888 Fax: 001 415 433 0289

2. Patient DARREN SCRINE, 30, has virtually no trace of CML after taking STI571. Darren, a website technical manager from Peterborough, was diagnosed in March 2000 and started on the Newcastle drug trials on June 30 this year. On September 27, a bone marrow biopsy showed the drug had cleared 98% of the disease. Darren runs the CML European Support Group. You can contact him on 0780 1161809.

Notes to journalists:

1. For further details of the Newcastle trials, see www.ncl.ac.uk/cml

2. The American Society for Hematology meeting in San Francisco (until December 5) will be the first meeting at which data from the UK will be presented.

3. Currently the only known 'cure' for chronic myeloid leukaemia (CML) is a bone marrow transplant. In patients in the early 'chronic phase' of the disease the usual treatment for those who do not have a bone marrow transplant is interferon alpha given as a self administered daily injection. However, interferon treatment is inconvenient and often produces unpleasant side effects. The response of the disease to treatment is assessed by taking a small bone marrow sample every few months and checking what proportion of the cells are 'Philadelphia-positive' - an indicator of how much leukaemia remains. With interferon treatment only about 5-10% of patients clear the leukaemia completely and become 'Philadelphia negative' but the survival rate of such patients is greatly improved.

4. In one of the studies reported at the ASH meeting, 532 patients who had not had any response to interferon, or who could not tolerate the drug, were treated with STI571. 290 of those patients have received the drug for over 6 months and were reported at the meeting. Some degree of reduction in the Philadelphia chromosome was seen in over 50% of patients and remarkably over 30% of all patients became Philadelphia negative. Only time will tell whether these exciting initial results translate into improved survival but there is great optimism that this will be the case.

5. In the UK the only hospitals initially taking part at the end of 1999 were the Royal Victoria Infirmary in Newcastle and the Hammersmith. Early this year Nottingham joined in and now the drug is also available through hospitals in Liverpool, Glasgow and Dublin (6 centres in total). For certain resticted studies an additional 7 hospitals are now taking part (Leeds, Manchester, Cambridge, Plymouth, Barts, Kings, Birmingham).

6. In total over 3,000 patients worldwide have been treated with STI571 to date, most of these patient have been recruited to studies only in the last 6 months.

7. STI571 is made by Novartis (Basel), and was developed in collaboration with Dr Nick Lydon and Professor Brian Druker. For further details see www.novartisoncology.com/

8. STI571 was first given to a human subject in June 1998 in Portland, Oregon under the direction of Professor Brian Druker, who is the key figure in the clinical development of this compound. Professor Druker ensured that it entered clinical trials despite some initial reservations. For further details see: www.discoveryhealth.com/DH/ihtIH/WSDSC000/8096/24097.html

9. STI571 is now being used in other types of cancer such as cancer of the bowel and lung with some very promising initial results.

10. Dr O'Brien, Dr Druker and others are now investigating the combination of STI571 with other drugs to further improve on the results seen with STI571 alone. It may be that in due course CML could be controlled by two or three STI571-like drugs and even if the disease cannot be cured it may be controlled indefinitely and allow patients a normal life span.

11. There is now great interest in developing similar compounds that work in a similar way to STI571 for the treatment of other types of cancer.

12. A problem facing sufferers with CML in the UK and throughout the world is the availability of STI571 in the next year. It is expected that even with fast-tracking, the US Food and Drug Administration (FDA) will not grant a licence until summer of 2001 for the United States and the European equivalent, the European Medicines Evaluation Authority (EMEA), is usually 6 months slower, a situation that many doctors and patients in Europe find unacceptable. The UK's National Institue for Clinical Excellence (NICE) is currently considering the drug but until the cost of STI571 is announced the issues of NHS funding and availability remains uncertain.

Ends

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