Treatment of Newly Diagnosed Glioblastoma with Concomitant and Adjuvant Temozolomide and Radiotherapy

Abstract

Background and aim:In the UK, the current management of high-grade gliomas consists of maximal surgical debulking, where possible, followed by radiotherapy. A large, randomized, multicenter trial assessing the addition of temozolomide to radiotherapy found a significant increase in median survival of the order of 2.5 months in favor of the combined treatment (14.6 vs 12.1 months; p < 0.001). Our center has considerable experience with temozolomide and has treated patients with a regimen similar to that used in the above trial. The aim of this study was to confirm whether these results are translated into a benefit when used in clinical practice in the UK.

Material and methods:We present a retrospective study of 86 patients treated for glioblastoma with radiotherapy with or without temozolomide between 1998 and 2003. A search of our radiotherapy database was undertaken and patient records were accessed for histopathology, chemotherapy, and radiotherapy information. Patients who were diagnosed with glioblastoma and who did not receive radiotherapy or only received a palliative dose were excluded from the study. Radiotherapy was administered at a dosage of 60–65Gy in 30–37 fractions over 6 weeks. Temozolomide was administered orally at a dosage of 75 mg/m²daily for 6 weeks throughout the radiotherapy, followed by adjuvant temozolomide given for 6 cycles on days 1–5 of a 28-day cycle (150–200 mg/m²/day).

Results:Eighty-six patients (59 male and 27 female; mean age = 55.1 years, range 25–72) with glioblastoma were planned to receive treatment with a radical dosage of radiotherapy. Forty-eight patients (56%) underwent surgical debulking. Forty-nine patients (57%) received concurrent temozolomide and radiotherapy followed by adjuvant temozolomide (median number of cycles received was three). Thirty-seven patients (43%) initially received radiotherapy alone, although nine of those received chemotherapy on further disease progression. Three patients died before treatment was completed. The decision to treat with temozolomide was influenced by the availability of the drug. There were no identifiable patient factors influencing the decision for radical radiotherapy alone or combined radiotherapy and temozolomide. Patients treated with concurrent temozolomide and radiotherapy had a significantly better median survival of 13 months compared with 8 months for those treated with radiotherapy alone (p < 0.003).

Conclusion:The addition of temozolomide to the standard treatment of radiotherapy for glioblastoma improved overall survival. This study shows that the published phase III results in a selective group of patients can be replicated in everyday practice and that the combined regimen is both practical and effective.