"In 25 years of academic cancer medicine, it is the first time that I have witnessed such a progress in any of the deadliest forms of human cancers.

The European Organisation for Research and Treatment of Cancer (EORTC) collaborated with the National Cancer Institute of Canada (NCIC) Clinical Trials Group in conducting the research, which is published in two companion papers in the March 10 edition of the New England Journal of Medicine.

New Standard of Care Possible

Molecular analyses of the tumor allowed for the identification of those patients most likely to benefit from this type of treatment. The findings could lead to a new standard of care for patients with this fast-growing and devastating cancer.

Primary tumors 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 tumor 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 tumor that usually has a fatal outcome.

Clear Improvement of Survival

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 analyzed the functionality of a gene responsible for DNA repair, the MGMT gene -- the findings would be even more dramatic, as almost half of those patients whose tumors 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.

Exceptional Model of Cooperation

"This is the first trial to demonstrate that we can truly impact this devastating disease with chemotherapy," says the lead author and trial initiator Roger Stupp, MD, of the University Hospital Multidisciplinary Oncology Centre in Lausanne, Switzerland. "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," Dr. Stupp says.

"Without the close collaboration between the hospital based research laboratory and the leading clinicians, this interdisciplinary success would never have been possible," adds Monika Hegi, PhD, signing author for the translation research work and leader of the laboratory of Tumor Biology and Genetics of the University Hospital Lausanne Neurosurgery department.

"I hope this example will stimulate a closer collaboration between basic and clinical research in the future," remarks Dr. Hegi, who is also project leader at the National Center of Competence in Research (NCCR Molecular Oncology).

"In 25 years of academic cancer medicine, it is the first time that I have witnessed such a progress in any of the deadliest forms of human cancers," says co-investigator and radiation therapy protocol leader, René-Olivier Mirimanoff, MD, of the Radiation Oncology Department of the University Hospital in Lausanne, Switzerland. "The study has also been an exceptional model of multidisciplinary as well as international cooperation, with such an outstanding input of so many participants," Dr. Mirimanoff notes.

Very Few Side Effects

"Until now, there have been few treatment options for glioblastoma patients," says Dr. Gregory Cairncross, a pioneer in neurooncology research and one of the study's primary investigators and head of the Department of Clinical Neurosciences at the University of Calgary in Alberta, Canada.

"The results of this trial will dramatically improve treatment and outcome for many of these patients and will open the door to further trials to expand this treatment combination," Dr. Cairncross continues. "The key to the new therapy's effectiveness is that temozolomide causes very few side effects and is well tolerated by patients. This means patients can take the drug every day during their radiation treatment instead of once every eight weeks -- the common dosage for other chemotherapy drugs," he points out.

"This landmark study represents the most important advance in the management of glioblastoma since radiotherapy was shown to be of benefit over 35 years ago," comments Dr. Warren Mason, a lead investigator in Canada and head of the neuro-oncology unit at the Princess Margaret Hospital in Torono, Ontario/Canada.

"This study also identified MGMT the first clinically relevant molecular marker for glioblastoma which not only serves as a prognostic factor for survival, but also as a predictor for response to chemotherapy. This observation paves the way for using the unique tumor genetic signature as a guide for individualizing therapy and optimizing outcome," Dr. Mason says.