Temozolomide/RT Effective Against GBM

NEW ORLEANS—The chemotherapy drug temozolomide (Temodar) combined with radiation therapy more than doubled the 2-year survival rate in patients with glioblastoma multiforme (GBM), compared with radiation alone, according to data presented at the plenary session of the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 2).

"This is the first study to demonstrate a statistically significant and clinically meaningful survival advantage for chemotherapy in a homogeneous group of glioblastoma patients," said Roger Stupp, MD, attending physician, Multidisciplinary Oncology Center, University of Lausanne Hospitals, Lausanne, Switzerland. He represented the European Organization for Research and Treatment of Cancer (EORTC) Brain Tumor and Radiotherapy Groups and the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG).

He noted that these phase III findings confirm the efficacy and tolerability results of a prior phase II study (Stupp et al: J Clin Oncol 20:1375-1382, 2002).

Median survival for GBM is less than 1 year after diagnosis, and standard treatment has been surgery followed by radiation therapy. Although PCV chemotherapy (procarbazine [Matulane], lomustine [CeeNU], and vincristine) has also been used, clinical trials have not found this regimen to provide a clear survival benefit, Dr. Stupp said. However, in the new study, temozolomide extended median survival by 2.5 months.

In the phase III trial, Dr. Stupp and his colleagues randomized 573 patients into two groups. All were newly diagnosed with GBM and had gone through biopsy or resection no more than 6 weeks previously. One group received the standard therapy for GBM in Europe and Canada: daily radiation therapy of 200 cGy for 30 days, for a total dose of 60 Gy. The other group received the same radiation therapy plus temozolomide. Planned dosage was 75 mg/m² orally every day, 7 days a week, for 6 to 7 weeks during radiotherapy, then 150 to 200
mg/m² orally on days 1 to 5 every 28 days for as many as six cycles.

The primary endpoint was overall survival (based on intention to treat). Secondary endpoints included progression-free survival, quality of life, safety and tolerability, and an economic analysis.

Median overall survival was 14.6 months in the temozolomide group vs 12.1 months in the standard-therapy group. Two-year survival was 26% in the temozolomide group vs 10% in the standard-therapy group. Progression-free survival after 1 year was 27% in the temozolomide group vs 9% in the control group. Progression-free survival after 2 years was 11% and 2%, respectively. "The benefit is consistent in all subgroups of patients," Dr. Stupp said.

The researchers considered the chemotherapy safe and well tolerated. Only 6% of patients in the temozolomide arm dropped out of the study due to toxicity. The standard-therapy group had no grade 3-4 hematological toxicities; the treatment group had a 4% incidence of grade 3-4 neutropenia and a 3% incidence of thrombocytopenia. Two thirds of the patients in both arms had fatigue during radiotherapy.

Although temozolomide led to statistically significant improvements in overall survival and progression-free survival, nearly three quarters of the temozolomide-treated patients still died within 2 years. "Further improvement in treating this deadly disease is still necessary," Dr. Stupp said. "This trial has clearly shown that current therapies can impact this disease. This result should encourage patients and physicians alike to participate in innovative and collaborative clinical research."