Navigation Links
Trial combining anti-cancer drug and radiotherapy may lead to treatment for brain tumor

Results from a clinical trial of a new treatment for glioblastoma suggest that researchers may have found a new approach to treating this most aggressive of brain tumours, as well as a potential new biological marker than can predict the tumour's response to treatment.

Presenting the research to the 2013 European Cancer Congress (ECC2013) [1] today (Monday), Professor Wolfgang Wick will say that combining radiotherapy with an anti-cancer drug called APG101 a fusion protein similar to an antibody blocks a cell-signalling pathway called CD95 that plays a crucial role in the development of the cancer. "Blocking the CD95 system represents a new way of tackling glioblastoma a cancer that has few available treatment options," he will say.

A total of 84 glioblastoma patients, who had already received initial treatment including radiotherapy and whose cancer had recurred, were randomised in the phase II clinical trial to receive either radiotherapy alone, or radiotherapy together with an intravenous dose of 400 mg of APG101 once a week [2]. Their average age was 57, and the trial was carried out between December 2009 and September 2011 in 25 centres in Germany, Austria and Russia.

Twenty-one percent of patients who were treated with the combination of radiotherapy and APG101 were still alive six months after treatment, compared to four percent of those that were treated with radiotherapy alone. After two years, 22% of patients receiving the combination treatment were alive compared to seven percent of patients who did not receive it. The risk of death was reduced by 40% in the experimental treatment group, although this did not quite reach statistical significance.

Prof Wick, Chairman of the Neurooncology Programme at the National Centre for Tumour Diseases and Professor of Neurooncology at the University of Heidelberg (Germany) will tell the conference: "Glioblastoma is a very aggressive, fast-growing tumour that shows an infiltrative growth, making local therapies of very limited efficacy. The tumour is also resistant to all current chemotherapy treatments, and has devastating effects on the quality of life of patients. This brain tumour affects two to three people per 100,000, and is associated with a very poor prognosis, with an overall survival of 12 months.

"This is the first controlled trial of re-irradiation and the first performed in glioblastoma patients up to now. It was already known that APG101 might be an innovative approach for treating glioblastoma, but the size of the protein molecule was potentially too large to cross the protective bloodbrain barrier and target the tumour. Radiotherapy opens up this barrier and may therefore be an effective vehicle for this compound."

APG101 plays a major role in the blocking of the CD95/CD95L system. CD95 is a protein that acts as a receptor on the surface of cells. When this cell receptor binds with the CD95 ligand (CD95L) another protein it prompts the cell to die.

"Until 2008, it was thought that activating this system represented a potential strategy for treating glioblastoma," Prof Wick will explain. "But then it was realised that this made the cancer cells resistant to cell death and actually increased their ability to proliferate and spread to other tissues. Therefore, inhibition rather than activation is now considered a meaningful hypothesis to be tested, particularly in brain tumours."

The researchers found that patients with tumours expressing the CD95L protein had a worse prognosis than patients with tumours that did not express CD95L. However, CD95L-expressing tumours responded better to the APG101 combination treatment, with an overall survival of 11.5 months for these patients, compared to 8.2 months for patients without an active form of the protein.

"This also implies that CD95L would be one of the first predictive markers in neuro-oncology, which may help to define patients with glioblastoma deriving benefit from the new therapeutic strategy," Prof Wick will say. "At present, there is paucity of predictive markers that tell us how to treat patients in the glioma field."

Prof Wick and his colleagues are continuing their research: "We still need to improve our understanding of how APG101 is acting. We also envisage testing new combinations of APG101 and radiotherapy plus temozolomide, a chemotherapy drug used for treating glioblastoma. There is a need to explore the mode of action as well as the mode of acquired resistance to the compound in patients," he will conclude.

President of ECCO, Professor Cornelis van de Velde, commented: "Although these are preliminary results, they are very interesting because glioblastoma is such a fast-growing tumour and there are so few available treatment options for these patients. An improvement in the percentage of patients surviving for six months after being treated with the combination of radiotherapy and APG101 is significant. Furthermore, the discovery that CD95L is likely to be a predictive marker for patient response may help us to target treatments more effectively. The findings presented today are a further advance along the difficult path of finding a successful way to treat this aggressive cancer."


Contact: José Abad
ECCO-the European CanCer Organisation

Related biology news :

1. Study jointly led by UCSB researcher supports theory of extraterrestrial impact
2. Ottawa researchers to lead world-first clinical trial of stem cell therapy for septic shock
3. Canadian Journal of Cardiology publishes new atrial fibrillation guidelines
4. New clinical trial explores novel noninvasive colon cancer screening test
5. Clinical trial launches to see whether vitamin D helps treat multiple sclerosis
6. Trial seeks improved lung-cancer screening by combining imaging and biomarkers
7. Trial launched into curry chemicals cancer-fighting properties
8. Molecule found that inhibits estrogen, key risk factor for endometrial and breast cancers
9. VolitionRX Raises Over $1 Million To Begin Clinical Trials of Blood Based Diagnostic Tests
10. Delivery of gene-therapy for heart disease boosted 100-fold; now in 100-patient trial
11. Clinical trials for Alzheimers disease preventative drug to begin early 2013
Post Your Comments:
(Date:10/29/2015)... Oct. 29, 2015  Connected health pioneer, Joseph ... explosion of technology-enabled health and wellness, and the business ... The Internet of Healthy Things . ... smartphones even existed, Dr. Kvedar, vice president, Connected Health, ... care delivery, moving care from the hospital or doctor,s ...
(Date:10/27/2015)... Oct. 27, 2015 In the present market ... concern for various industry verticals such as banking, healthcare, ... the growing demand for secure & simplified access control ... such as hacking of bank accounts, misuse of users, ... such as PC,s, laptops, and smartphones are expected to ...
(Date:10/26/2015)... , October 26, 2015 /PRNewswire/ ... --> adds Biometrics ... to 2021 as well as Emerging ... research reports to its collection of ... . --> ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... 2015 , ... Copper is an essential micronutrient that all ... copper is also toxic to cells. With a $1.3 million award from the ... a systematic study of copper in the bacteria Pseudomonas aeruginosa (P. aeruginosa), a ...
(Date:11/24/2015)... --> --> ... Synthesis Market by Product & Services (Primer, Probe, Custom ... RNAi), End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) - ... is expected to reach USD 1,918.6 Million by 2020 ... of 10.1% during the forecast period. Browse ...
(Date:11/24/2015)... , November 24, 2015 ... recent market research report released by Transparency Market Research, ... expand at a CAGR of 17.5% during the period ... Testing Market - Global Industry Analysis, Size, Volume, Share, ... global non-invasive prenatal testing market to reach a valuation ...
(Date:11/24/2015)... ... November 24, 2015 , ... In ... paramount. Insertion points for in-line sensors can represent a weak spot where leaking ... 781/784 series of retractable sensor housings , which are designed to tolerate extreme ...
Breaking Biology Technology: