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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>