Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme.

PURPOSE: Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM.

PATIENTS AND METHODS: One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m(2)/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m(2) on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53).

RESULTS: Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild.

CONCLUSION: TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.