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Systemic Pre-Surgical Treatment Can Prolong Survival Of Kidney Cancer Patients

e and primary tumours.

'Our findings indicate that this treatment approach might be applicable to a wide range of patients with renal cell carcinoma, and that we might be able to use systemic treatment, before surgery, to treat many more people with metastatic disease successfully. It could become a new paradigm of treatment for the disease, instead of the current up-front surgery followed by systemic therapy.'

Prof Jonasch and his colleagues aim to enrol a total of 50 patients in the study, which they hope to complete by early 2007. So far they have 32 patients, and have evaluated tissue from 20. The patients were previously untreated, did not have brain metastases and had not undergone kidney surgery.

They gave the patients bevacizumab intravenously once every two weeks for four doses, and erlotinib orally every day for eight weeks. Two weeks after the last dose of erlotinib and four weeks after the last dose of bevacizumab, they surgically removed the kidney tumour (cytoreductive nephrectomy). Patients who had stable disease or a response one month after the surgery were restarted on the treatment, which was continued until the cancer started to progress.

When the researchers looked at the protein expression of key signaling molecules involved in controlling cell proliferation, survival and migration, they could not find any difference between tissues from treated patients and tissues from their tissue bank which had come from untreated patients. The one exception was a slight increase in the expression of AKT in the treated group, which meant that blocking the VEGF signaling pathway with bevacizumab might have resulted in feedback to the AKT pathway, which is known to be involved in cell signaling.

'At the moment, we don't understand what mechanisms are operating to bring about the response we have observed in patients,' said Prof Jonasch. 'We are looking at a number of other biomarkers to look for a 'signal' tha
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