Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Systemic treatment before surgery for kidney cancer prolongs patients’ survival

10.11.2006
Preliminary results from a phase II clinical trial have provided the first evidence that treating people with kidney cancer with bevacizumab and erlotinib [1] before surgery is safe, effective and may prolong patients’ survival.

Renal cell carcinoma [2] (kidney cancer) is notoriously hard to treat, especially once it has started to spread to other sites in the body. If it has metastasised to the lymph nodes, five-year survival is between 5-15% and if it has spread to other organs the five-year survival is less than five per cent.

Studies have been carried out investigating the use of targeted therapies, such as bevacizumab and erlotinib, after surgery, but researchers at the University of Texas MD Anderson Cancer Center, USA, are conducting the first trial to investigate their use before surgery.

Assistant professor of medicine, Eric Jonasch, told a news briefing at the EORTC-NCI-AACR [3] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Thursday 9 November) that, as of June 2006, the 20 patients enrolled in the trial within the previous year were all still alive. One had complete remission in the primary tumour and stable disease in bone metastases, three patients were in partial remission, 13 patients had stable disease and three patients had progressive disease.

“Without this treatment I would have expected most of them to have progressive disease by now,” said Prof Jonasch. “The average time to progressive disease is usually about twelve weeks, and I would argue that our patients have more aggressive disease as they have not had the benefit of any previous treatment.

“These early data suggest pre-surgical treatment with bevacizumab and erlotinib is safe and efficacious in patients with previously unresected, untreated metastatic renal cell carcinoma, with shrinkage of both the metastatic disease 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 signalling 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 signalling pathway with bevacizumab might have resulted in feedback to the AKT pathway, which is known to be involved in cell signalling.

“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’ that can be associated with the response. We want to discover how these targeted therapies produce a response in renal cell carcinoma, what molecules and genes are controlling disease resistance and response, and, specifically, what role is played by the protein VHL, which is frequently mutated in patients with kidney cancer and which is known to be an important driver of angiogenesis.”

In addition, Prof Jonasch and his team are running similar trials with two other targeted therapies, sorafenib and sunitinib.

He said: “The main aim of this study was to look at the efficacy and safety of using these targeted therapies before surgery, and our results have shown that there were few side effects and that it prolonged the survival of our patients.”

1.Bevacizumab is a monoclonal antibody that inhibits angiogenesis; it is marketed as Avastin. Erlotinib targets EGF, blocking the signal that tells cells to divide; it is marketed as Tarceva.

2.Renal cell carcinoma is more common in men than in women, affecting an average of 4.7 men and 2.5 women in every 100,000 in the world (age standardised rate, world), and killing an average of 2.3 men and 1.2 women in every 100,000 (ASR, world). It is much more common in developed countries, with an average incidence of 10.4 per 100,000 in men, compared to 2.1 per 100,000 in less developed countries. (Source: Globocan 2002)

3.EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

Emma Mason | alfa
Further information:
http://www.eortc.org

More articles from Health and Medicine:

nachricht Electrical 'switch' in brain's capillary network monitors activity and controls blood flow
27.03.2017 | Larner College of Medicine at the University of Vermont

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>