Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First results from novel anti-angiogenic drug trial in patients

20.11.2002


’Surprisingly effective’ says French research team



A new drug that targets tumour blood vessels has produced a surprisingly effective response in its first patient study - shrinking the tumours in a number of patients treated so far, according to researchers carrying out the study at the Institut Gustave Roussy in Villejuif, France.

The drug, SU011248[1], which is given in capsule form, is a signal transduction inhibitor designed to act against several abnormally behaving enzymes along the cellular signalling pathway.[2]


Results of the first Phase I study were presented today (Wednesday 20 November) at the EORTC-NCI-AACR[3] Symposium on Molecular Targets and Cancer Therapeutics, in Frankfurt.

Patients in the study had a range of advanced cancers[4], which had failed to respond to all other therapies: in many cases at least three different types of treatment had been tried.

Lead researcher Dr Eric Raymond told a news briefing: "Any activity in this situation is very promising since everything else has failed. But, we did not expect to see such a high number of responses[5] in a range of cancers."

He said that the Phase I study would continue for the next six months or so. Phase II and III studies would start immediately afterwards and would include a formal analysis of the response rate - an analysis that was inappropriate for the Phase I study, which began with very low doses of the drug.

The drug is a newcomer in the field of anti-angiogenics – drugs designed to damage tumours by attacking the network of blood vessels that ’feed’ them. Although it has been a major research field over the last decade or more, angiogenesis has not so far lived up clinically to its early research promise. But, the response in this study provides evidence that anti-angiogenics may yet have a future.

Dr Raymond said: "Initially we thought that the drug would be an angiostatic agent that stabilises tumours, rather than an angiotoxic agent that actively shrinks tumours. Angiostatic compounds were associated with a low level of response, but angiotoxics are much more promising in inducing responses. We were happily surprised right from the first patient response – a reduction of more than 50% in the tumour for six months in someone with a renal cancer that had recurred and who also had adrenal and lung secondaries that had not responded to immunotherapy."

The drug has shown activity in a range of tumours, including renal and gastro-intestinal cancers, so the researchers believe that it may be suitable for other tumour types beyond those in the Phase I study. "It seems that the drug is killing the blood vessels into tumours regardless of the tumour type," Dr Raymond said.

However, it did not appear effective against brain metastases, indicating that, like many drugs, it may not be able to pass across the blood-brain barrier.

Dr Raymond said that a lot more work needed to be done on dosing and on toxicity as the drug affected normal blood vessels as well as tumour vessels. It was also vital to get information on toxicity after repeated treatment cycles to avoid discovering late delayed cumulative side effects.

Among the side effects already seen were two unusual phenomena. The drug tanned the skin in several patients, turning it a golden colour (the drug is yellow and accumulates in the skin). But this effect wore off within a week of stopping treatment. Patients with high plasma levels of the drug suffered progressive hair discoloration. But this too was reversible. Dr Raymond said that the discoloration was likely to be due to the drug’s effect in inhibiting the MAP kinase signalling pathway and preventing the activation of a gene that triggers melanin activity.

He concluded that if the drug’s activity held up in further trials it had the potential to be a potent new weapon. "It is one of the first angiotoxic drugs with anti-tumour effects. In fact, we had too much effect in higher doses in some patients resulting in tumour necrosis that required surgery. So this drug is teaching us a lot about the potential efficacy and, just as important, about the adverse effects of new anti-angiogenic agents."


###
Notes:
[1] SU011248 is a novel orally bioavailable indolinone developed by Sugen, a California-based company that was acquired in 1999 by Pharmacia.

[2] The drug inhibits activity of the following enzymes: VEGFR (Flk-1KDR), PDGFR alpha and ß, Flt3, c-kit tyrosine kinase

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

[4] Cancers included in the study were: renal, non small-cell lung, neuro-endocrine, uterine, angiosarcoma, mesothelioma, pancreatic, breast, colorectal and nasopharyngeal.

[5] Response was defined as a reduction in tumour volume of more than 50% as measured by CT scan.

Further information:
Margaret Willson (media information officer)
Tel: 44-153-677-2181
Fax: 44-153-677-2191
Mobile: 44-797-385-3347
Email:m.willson@mwcommunications.org.uk

From: 16:00hrs CET Monday 18 November to 17:00hrs CET Friday 22 November
EORTC-NCI-AACR symposium press office:
Tel: 49-697-5757-3294
Fax: 49-697-5757-3451

Margaret Willson | alfa

More articles from Health and Medicine:

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

nachricht Scientists find new approach that shows promise for treating cystic fibrosis
14.03.2019 | NIH/National Heart, Lung and Blood Institute

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: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Levitating objects with light

19.03.2019 | Physics and Astronomy

New technique for in-cell distance determination

19.03.2019 | Life Sciences

Stellar cartography

19.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>