ArticlesTemozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
Introduction
Glioblastoma is the most frequent primary brain tumour and is mainly seen in people older than 60 years. Median survival is less than 1 year.1, 2 Chemoradiotherapy with temozolomide became the standard of care in 2004, but its introduction was based on a pivotal study in which patients were aged 70 years or younger; increasing age was found to be a negative prognostic factor.3, 4 Elderly and frail patients might, therefore, not be viewed as candidates for combined therapy, and extensive treatment might not be seen as justifiable owing to the short survival.5, 6, 7, 8, 9, 10
Alternatives to the standard 6 weeks of radiotherapy that are associated with similar or improved survival and quality of life would be beneficial. Outpatient treatment or short treatment times could also lessen demands on medical resources and reduce the risk of treatment being withheld. Chemotherapy with temozolomide, an oral alkylating agent, has been efficacious as a treatment for glioma with low risk of toxic effects11, 12, 13 and hypofractionated radiotherapy has been advocated.14, 15 In contrast to radiotherapy, temozolomide chemotherapy can be administered from local hospitals and can be started quickly after diagnosis.
To define an evidence-based treatment recommendation for patients aged 60 years or older with glioblastoma, the Nordic Clinical Brain Tumour Study Group (NCBTSG) did a randomised trial to compare survival, health-related quality of life, and safety with single-agent temozolomide chemotherapy, hypofractionated radiotherapy, or standard radiotherapy.
Section snippets
Patients
Between Feb 2, 2000, and June 18, 2009, we recruited patients from 28 centres treating patients with brain tumours (mainly oncology departments) in Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey, to which patients were referred after neurosurgery. Patients with newly diagnosed, histologically confirmed glioblastoma (WHO grade IV astrocytoma) and aged 60 years or older were eligible. To resemble the characteristics of patients seen in clinics, patients with WHO performance
Results
342 patients were enrolled overall. 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, and standard radiotherapy n=100) and constitute the cohort for comparisons with standard radiotherapy. 51 further patients from four centres that did not offer standard radiotherapy were randomised across only the temozolomide (n=26) or hypofractionated radiotherapy (n=25) groups. Thus, 242 patients were assessed in comparisons of temozolomide (n=119
Discussion
Our trial confirms that the overall prognosis for elderly patients with glioblastoma is poor, particularly in patients older than 70 years treated with standard radiotherapy (panel). We found that temozolomide chemotherapy is a potential alternative to radiotherapy in elderly and frail patients. Of note is that a substantial number of patients were unable to complete the planned standard radiotherapy regimen, which could partly explain the inferior survival in this group. Radiotherapy was
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