A large international study conducted by the European Organisation for Research and Treatment of Cancer (EORTC) in collaboration with the National Cancer Institute of Canada (NCIC) Clinical Trials Group demonstrated that the addition of a novel chemotherapy agent, Temozolomide (brand name: Temodal®) to radiation therapy increases survival in patients suffering from glioblastoma, a very aggressive form of a brain tumour.
Further, molecular analyses of the tumour allowed for the identification of those patients most likely to benefit from this type of treatment. The findings are leading to a new standard of care for patients with this fast growing and devastating cancer. The results of this landmark trial are published in two companion papers in this weeks' edition of the New England Journal of Medicine (publication date: 10 March 2005).
Primary tumours originating in the brain account for less than 5% of all cancer diagnoses. However, brain cancer frequently affects previously healthy younger men and women in the middle of their most active life. Glioblastoma is the most common type of primary malignant brain tumour in adults with a yearly incidence of 5-7 persons per 100.000. Thus in the European Union approx. 20'000 new patients are diagnosed every year. Glioblastoma is a rapidly growing malignant brain tumour and usually has a fatal outcome.
Prior to the discovery of this new therapy, the average life expectancy of patients with glioblastoma was about 1 year. The results of this study demonstrate a clear improvement of survival. At 2 years only 10% of patients treated with radiotherapy alone were alive, compared to 26% of patients receiving the combination of both radiotherapy and temozolomide chemotherapy. If patients were to be selected according to their molecular profile - the investigators analysed the functionality of a gene responsible for DNA repair, the so called MGMT gene - the improvement is even more dramatic, as almost half of those patients whose tumours carry an inactivated MGMT gene are alive after 2 years. Importantly, the study also showed that this new combined therapy did not impact negatively on the patients' quality of life. Health-related quality of life has become an increasingly important endpoint in cancer studies.
In this trial, almost 600 patients were randomised within less than one and a half years. This rapid accrual and final success would not have been possible without well-established structures for academic clinical research, like the EORTC and NCIC Clinical Trials Group. Recently implemented new regulations in Europe with an increased administrative burden, complex liability and insurance issues as well as exploding costs have become a threat for future successful conduct of clinical trials. This example illustrates that progress in cancer treatment requires well-functioning international collaborative networks and integrated laboratory-based science.
The EORTC also assembled a laboratory research team that succeeded in identifying a molecular change in the tumour that predicts benefit from this new therapy. Future brain tumour trials by the EORTC will continue to integrate clinical and basic research to further refine the molecular basis of brain cancer, find new therapeutic targets, and develop and test new treatments.
"This is the first trial to demonstrate that we can truly impact this devastating disease with chemotherapy. This is only a first step toward cure of brain cancer patients and should now fuel interest, continued international collaboration and research to further improve the outcome of these patients", says the lead author and trial initiator Roger Stupp, MD for the University Hospital Multidisciplinary Oncology Centre in Lausanne, Switzerland.