A large-scale randomised clinical trial to investigate the effectiveness of thalidomide as a treatment for lung cancer is set to begin at the end of February 2003.
The Cancer Research UK-funded trial is the third stage in tests on a thalidomide and chemotherapy treatment for Small Cell Lung Cancer – a notoriously difficult type of lung cancer to treat. Around 400 patients will be recruited to take part.
The decision to go ahead with the final trial follows encouraging preliminary results from a smaller trial started in 2000. Forty per cent of the patients on that trial survived for more than a year. This compares well with the usual rate of 21 per cent for one-year survival.
Thalidomide hit the headlines in the 1960s when it was discovered that it caused birth defects by limiting blood flow to developing limbs.
The current trial, led by Dr Siow Ming Lee, who is based at University College London and Middlesex Hospital, will investigate this property of blood flow limitation to see if it can offer hope of new treatments to lung cancer patients.
Dr Lee believes that thalidomide not only stops new tumour blood vessel growth – preventing cancer spread and tumour growth – but that it also has immune stimulating properties against the cancer cells and stabilises existing blood vessels.
The stabilised vessels allow a smooth flow of blood to the core of the tumour – delivering cancer killing chemotherapy drugs and the oxygen needed for the chemotherapy to work effectively.
The blood flow to tumours normally pulses rather than flows – reducing the effectiveness of the chemotherapy treatment.
Dr Lee says: “Results from earlier tests have been encouraging. The outlook with existing treatments for small cell lung cancer remains poor – this is why we must look for innovative methods of treating the disease.”
In the earlier tests patients were given chemotherapy with thalidomide. This large scale test will investigate the advantages of giving thalidomide with chemotherapy compared to chemotherapy alone.
“We need to investigate whether the combined treatment is more effective than standard chemotherapy alone. Even minor improvements at this stage could result in many lives being saved in the future,” says Dr Lee.
Thalidomide also has a range of potential positive side-effects. A common symptom of the disease is rapid weight loss and fatigue. The drug stimulates weight gain, enhances appetite and improves sleeping patterns. All of these can significantly improve the quality of life for cancer patients.
While patients who undergo traditional chemotherapy treatment have a high remission rate, the cure rate is very low. In 1996 this form of lung cancer was responsible for around 9,000 deaths in the UK.
The trial will be run from a number of centres across the UK – including UCL Hospitals, The Whittington Hospital, Barts and The London.
Sir Paul Nurse, Chief Executive of Cancer Research UK, says: “The use of thalidomide offers us scope for optimism, any improvement we can get on the existing survival figures would be very welcome news.”
The Phase II trial was conducted with 25 patients. It should be noted that although it showed a one-year survival rate of 40 per cent, this figure may not directly translate to the survival figure for stage III.
During the Phase II trial 13 patients provided weight data. 42 per cent (8 patients) gained weight; 8 per cent (1 patient) maintained stable weight; and 23 per cent (4 patients) lost weight.
Other side effects of thalidomide are drowsiness, constipation, nausea, dizziness, headaches and skin rash.
Following chemotherapy, patients continue to receive thalidomide therapy in an attempt to keep residual tumour cancer in a dormant state by preventing it from establishing new blood vessels.
Researchers are already aware of thalidomide’s ability to starve cancers of the oxygen they need to grow and are using the drug in trials to treat Kaposi’s sarcoma, brain cancer and multiple myeloma.
SCLC accounts for about 25 per cent of all lung cancers, and is aggressive, quick growing and early to spread. In 1998 there were 38,800 cases of lung cancer. In 2001 there were33,500 deaths from lung cancer.
Angiogenesis is the term used to describe the growth of new blood vessels. Cancers need to grow their own blood vessels as they get bigger. Without its own blood supply, a cancer cannot continue to grow. Thalidomide is an anti-angiogenic – a drug that blocks the development of new blood vessels. Scientists also think angiogenesis may play a part in cancer spread. They have found that the newly developing capillary cells release substances that help the cancer cells to detach from the primary tumour and get into the blood stream. This will mean that the cells can travel to another part of the body and begin to grow there.
Further trials information for patients is available on CancerHelp UK. Patients interested in the trial should contact their doctor.