Combination therapy improves response in glioblastoma recurrence
Results from a clinical trial of a new treatment for glioblastoma suggest that researchers may have found a new approach to treating this aggressive brain tumor. These results were presented at the 2013 European Cancer Congress (ECC2013) in Amsterdam, The Netherlands.
Glioblastoma is an aggressive, fast-growing tumor with infiltrative growth, making local therapy ineffective. The tumor is resistant to all current chemotherapy treatments. Glioblastoma affects two to three people per 100,000, and has devastating effects on the quality of life of patients. The prognosis is very poor and overall survival is only 12 months.
The anticancer drug APG101, which is a fusion protein similar to an antibody, was potentially too large to cross the protective blood-brain barrier and target the tumor, but radiation therapy opens up the blood-brain barrier. APG101 can then cross into the brain and block the CD95/CD95L system, a cell-signaling pathway 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," said Wolfgang Wick, MD, Chairman of the Neurooncology Program at the National Centre for Tumor Diseases and Professor of Neurooncology at the University of Heidelberg in Germany.
A total of 84 patients with glioblastoma who had received initial radiation therapy but had cancer recurrence were randomized to receive radiotherapy alone or radiotherapy with an intravenous dose of 400 mg of APG101 once a week. Their average age was 57 years, and the trial was carried out between December 2009 and September 2011 in 25 centers in Germany, Austria, and Russia.
At 6 months after treatment, 21% of the patients who were treated with the combination of radiation therapy and APG101 were still alive, compared with 4% of those treated with radiation therapy alone. After 2 years, 22% of patients receiving the combination treatment were alive compared with 7% of patients treated with radiation therapy alone. The risk of death was reduced by 40% in the experimental treatment group, although this did not quite reach statistical significance.
Professor Cornelis van de Velde, president of the European Cancer Organisation, 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 6 months after being treated with the combination of radiotherapy and APG101 is significant.… The findings presented today are a further advance along the difficult path of finding a successful way to treat this aggressive cancer."
This study was sponsored by the company developing APG101, Apogenix GmbH, in Heidelberg, Germany.